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Skin laser surgery lawsuits increasing
Patients and their families sued dermatologists in 21% of 174 lawsuits filed for injuries caused by cutaneous laser surgery from 1985 through 2011. Only plastic surgeons were more likely to be defendants, accounting for 26% of cases.
The incidence of lawsuits for cutaneous laser surgery injury generally is on the upswing, increasing from five or fewer cases per year in 1985-1999 to a peak of 22 cases in 2010, Dr. H. Ray Jalian and his associates reported.
The majority of the cases involved laser hair removal (36%) and rejuvenation procedures (25%). The rejuvenation procedures included conventional ablative resurfacing, nonablative resurfacing, intense pulsed light, and the use of both ablative and nonablative fractional lasers. Plaintiffs won an average of $380,700 each in 51% of the 120 cases that reached a decision or settlement. That’s more than the average $275,000 indemnity payment across all medical specialties in a 2011 report, but the two studies used different methodologies. Dr. Jalian and his associates analyzed cutaneous laser surgery cases in the national Westlaw Next database of public records that included some form of legal pleading (JAMA Dermatol. 2013;149:188-93). The previous data included all resolved claims (not only those with legal pleadings) in all specialties (N. Engl. J. Med. 2011;365:629-36).
The physicians being sued included at least 12 other kinds of specialists, suggesting that a significant number of physicians offer or supervise laser skin treatments outside the scope of their specialty, wrote Dr. Jalian, a clinical fellow at the Wellman Center for Photomedicine, Massachusetts General Hospital, Boston.
General surgeons, family physicians, ob.gyns., and otolaryngologists each accounted for 5% of cases. Others included ophthalmologists (3%), orthopedic surgeons (2%), and specialists in radiology, anesthesia, physical medicine and rehabilitation, preventative medicine, and vascular surgery (1% each). Physician extenders (including physician assistants, nurse practitioners, registered nurses, aestheticians, and technicians) were laser operators or supervisors in 20% of cases.
Notably, physicians were sued even when they weren’t operating the laser, but were responsible for supervising the operator. Nonphysician operators (including physician extenders, chiropractors, podiatrists, and others) comprised 38% of operators and 26% of defendants. Physicians comprised 58% of operators and 74% of defendants. The training status of 5% of operators was unknown. (Percentages were rounded.)
After hair removal and skin rejuvenation, the most often litigated cases involved treatment of vascular lesions and telangiectasia (8% of cases) or treatment of leg veins (another 8%). Seven percent of cases involved tattoo removal, 4% involved neoplasms, 3% stemmed from treatment of scars, 2% involved laser treatment of pigmentary disorders, 1% were the use of a laser to treat pigmented lesions, and 6% were other procedures.
The most common injuries were burns (47%), scars (39%), and hypo- or hyperpigmentation (24%). Two percent of cases involved eye injuries, and at least two patients died due to complications of anesthesia.
The researchers offered several tips for physicians to reduce the risk of a lawsuit from skin laser surgery, including ensuring proper staff training and supervising delegated tasks. Be careful to evaluate skin type and select the correct laser parameters, they said. For some patients, it may be wise to do a test spot before starting laser treatment, even though solid data are lacking to support this. Follow guidelines from professional medical associations, such as the guidelines from the American Society for Laser Medicine, on delegating laser-related tasks to nonphysicians, the researchers added.
In general, federal regulations do not specify who can operate a laser, which procedures must be supervised by physicians, or where to perform procedures. Several states, including New York and Texas, do not require a license to perform laser hair removal, the most common type of laser skin surgery, the investigators noted. The lawsuits were filed in 30 states, the District of Columbia, and federal court, with the most cases in California (27), New York (23) and Texas (23).
Dr. Jalian reported having no financial disclosures. One of his coinvestigators has been a consultant and advisor for Zeltiq Aesthetics and a consultant for Unilever.
On Twitter @sherryboschert
Patients and their families sued dermatologists in 21% of 174 lawsuits filed for injuries caused by cutaneous laser surgery from 1985 through 2011. Only plastic surgeons were more likely to be defendants, accounting for 26% of cases.
The incidence of lawsuits for cutaneous laser surgery injury generally is on the upswing, increasing from five or fewer cases per year in 1985-1999 to a peak of 22 cases in 2010, Dr. H. Ray Jalian and his associates reported.
The majority of the cases involved laser hair removal (36%) and rejuvenation procedures (25%). The rejuvenation procedures included conventional ablative resurfacing, nonablative resurfacing, intense pulsed light, and the use of both ablative and nonablative fractional lasers. Plaintiffs won an average of $380,700 each in 51% of the 120 cases that reached a decision or settlement. That’s more than the average $275,000 indemnity payment across all medical specialties in a 2011 report, but the two studies used different methodologies. Dr. Jalian and his associates analyzed cutaneous laser surgery cases in the national Westlaw Next database of public records that included some form of legal pleading (JAMA Dermatol. 2013;149:188-93). The previous data included all resolved claims (not only those with legal pleadings) in all specialties (N. Engl. J. Med. 2011;365:629-36).
The physicians being sued included at least 12 other kinds of specialists, suggesting that a significant number of physicians offer or supervise laser skin treatments outside the scope of their specialty, wrote Dr. Jalian, a clinical fellow at the Wellman Center for Photomedicine, Massachusetts General Hospital, Boston.
General surgeons, family physicians, ob.gyns., and otolaryngologists each accounted for 5% of cases. Others included ophthalmologists (3%), orthopedic surgeons (2%), and specialists in radiology, anesthesia, physical medicine and rehabilitation, preventative medicine, and vascular surgery (1% each). Physician extenders (including physician assistants, nurse practitioners, registered nurses, aestheticians, and technicians) were laser operators or supervisors in 20% of cases.
Notably, physicians were sued even when they weren’t operating the laser, but were responsible for supervising the operator. Nonphysician operators (including physician extenders, chiropractors, podiatrists, and others) comprised 38% of operators and 26% of defendants. Physicians comprised 58% of operators and 74% of defendants. The training status of 5% of operators was unknown. (Percentages were rounded.)
After hair removal and skin rejuvenation, the most often litigated cases involved treatment of vascular lesions and telangiectasia (8% of cases) or treatment of leg veins (another 8%). Seven percent of cases involved tattoo removal, 4% involved neoplasms, 3% stemmed from treatment of scars, 2% involved laser treatment of pigmentary disorders, 1% were the use of a laser to treat pigmented lesions, and 6% were other procedures.
The most common injuries were burns (47%), scars (39%), and hypo- or hyperpigmentation (24%). Two percent of cases involved eye injuries, and at least two patients died due to complications of anesthesia.
The researchers offered several tips for physicians to reduce the risk of a lawsuit from skin laser surgery, including ensuring proper staff training and supervising delegated tasks. Be careful to evaluate skin type and select the correct laser parameters, they said. For some patients, it may be wise to do a test spot before starting laser treatment, even though solid data are lacking to support this. Follow guidelines from professional medical associations, such as the guidelines from the American Society for Laser Medicine, on delegating laser-related tasks to nonphysicians, the researchers added.
In general, federal regulations do not specify who can operate a laser, which procedures must be supervised by physicians, or where to perform procedures. Several states, including New York and Texas, do not require a license to perform laser hair removal, the most common type of laser skin surgery, the investigators noted. The lawsuits were filed in 30 states, the District of Columbia, and federal court, with the most cases in California (27), New York (23) and Texas (23).
Dr. Jalian reported having no financial disclosures. One of his coinvestigators has been a consultant and advisor for Zeltiq Aesthetics and a consultant for Unilever.
On Twitter @sherryboschert
Patients and their families sued dermatologists in 21% of 174 lawsuits filed for injuries caused by cutaneous laser surgery from 1985 through 2011. Only plastic surgeons were more likely to be defendants, accounting for 26% of cases.
The incidence of lawsuits for cutaneous laser surgery injury generally is on the upswing, increasing from five or fewer cases per year in 1985-1999 to a peak of 22 cases in 2010, Dr. H. Ray Jalian and his associates reported.
The majority of the cases involved laser hair removal (36%) and rejuvenation procedures (25%). The rejuvenation procedures included conventional ablative resurfacing, nonablative resurfacing, intense pulsed light, and the use of both ablative and nonablative fractional lasers. Plaintiffs won an average of $380,700 each in 51% of the 120 cases that reached a decision or settlement. That’s more than the average $275,000 indemnity payment across all medical specialties in a 2011 report, but the two studies used different methodologies. Dr. Jalian and his associates analyzed cutaneous laser surgery cases in the national Westlaw Next database of public records that included some form of legal pleading (JAMA Dermatol. 2013;149:188-93). The previous data included all resolved claims (not only those with legal pleadings) in all specialties (N. Engl. J. Med. 2011;365:629-36).
The physicians being sued included at least 12 other kinds of specialists, suggesting that a significant number of physicians offer or supervise laser skin treatments outside the scope of their specialty, wrote Dr. Jalian, a clinical fellow at the Wellman Center for Photomedicine, Massachusetts General Hospital, Boston.
General surgeons, family physicians, ob.gyns., and otolaryngologists each accounted for 5% of cases. Others included ophthalmologists (3%), orthopedic surgeons (2%), and specialists in radiology, anesthesia, physical medicine and rehabilitation, preventative medicine, and vascular surgery (1% each). Physician extenders (including physician assistants, nurse practitioners, registered nurses, aestheticians, and technicians) were laser operators or supervisors in 20% of cases.
Notably, physicians were sued even when they weren’t operating the laser, but were responsible for supervising the operator. Nonphysician operators (including physician extenders, chiropractors, podiatrists, and others) comprised 38% of operators and 26% of defendants. Physicians comprised 58% of operators and 74% of defendants. The training status of 5% of operators was unknown. (Percentages were rounded.)
After hair removal and skin rejuvenation, the most often litigated cases involved treatment of vascular lesions and telangiectasia (8% of cases) or treatment of leg veins (another 8%). Seven percent of cases involved tattoo removal, 4% involved neoplasms, 3% stemmed from treatment of scars, 2% involved laser treatment of pigmentary disorders, 1% were the use of a laser to treat pigmented lesions, and 6% were other procedures.
The most common injuries were burns (47%), scars (39%), and hypo- or hyperpigmentation (24%). Two percent of cases involved eye injuries, and at least two patients died due to complications of anesthesia.
The researchers offered several tips for physicians to reduce the risk of a lawsuit from skin laser surgery, including ensuring proper staff training and supervising delegated tasks. Be careful to evaluate skin type and select the correct laser parameters, they said. For some patients, it may be wise to do a test spot before starting laser treatment, even though solid data are lacking to support this. Follow guidelines from professional medical associations, such as the guidelines from the American Society for Laser Medicine, on delegating laser-related tasks to nonphysicians, the researchers added.
In general, federal regulations do not specify who can operate a laser, which procedures must be supervised by physicians, or where to perform procedures. Several states, including New York and Texas, do not require a license to perform laser hair removal, the most common type of laser skin surgery, the investigators noted. The lawsuits were filed in 30 states, the District of Columbia, and federal court, with the most cases in California (27), New York (23) and Texas (23).
Dr. Jalian reported having no financial disclosures. One of his coinvestigators has been a consultant and advisor for Zeltiq Aesthetics and a consultant for Unilever.
On Twitter @sherryboschert
FROM THE JOURNAL JAMA DERMATOLOGY
Major Finding: Plaintiffs and their families sued dermatologists in 21% of 174 lawsuits filed from 1985 through 2011 for injuries caused by cutaneous laser surgery.
Data Source: Retrospective review of records on 174 cases with legal pleadings in a national database.
Disclosures: Dr. Jalian reported having no financial disclosures. One of his coinvestigators has been a consultant and adviser for Zeltiq Aesthetics and a consultant for Unilever.
TV content affects children's behavior over time
Both the quantity and the content of television viewing by children may affect social behaviors long term, with effects that may last into adulthood, the results of two studies have shown.
In one randomized, controlled trial involving 565 preschool-aged children in the United States, coaching parents to reduce viewing of violence on the screen and to increase exposure to prosocial programming resulted in significantly less aggression and more prosocial behavior in the children after 6 months compared with the control group, effects that mostly were maintained at 12 months, Dr. Dmitri A. Christakis and his associates reported.
A separate longitudinal study from New Zealand followed 1,037 people from birth to age 26 years and found a significantly increased risk for antisocial outcomes in adults who had watched the most TV as children. Every extra hour of weeknight TV watching as children was associated with a 30% increase in the likelihood of having a criminal conviction by age 26, reported Lindsay A. Robertson and her associates.
Previous studies have shown that children imitate what they see on the screen and that reducing TV watching reduced aggression in 9-year-olds. Few studies have looked at preschoolers or at interventions aimed at content, Dr. Christakis said.
His study found that children fed a "media diet" deemphasizing violent programs and promoting viewing of programs that focus on sharing, caring, and education had Social Competence and Behavior Evaluation (SCBE) scores at 6 months that were 2 points better than in the control group, a significant difference that continued at 12 months (Pediatrics 2013;131:431-8).
The study did not try to change the amount of screen viewing, and both groups increased TV watching during the study, which often happens as children grow older. The likelihood of adults watching TV with their children did not differ between groups and remained stable throughout the study, despite efforts to promote coviewing, said Dr. Christakis, director of the center for child health, behavior, and development at Seattle Children’s Hospital and professor of pediatrics at the University of Washington, Seattle. He also is on the American Academy of Pediatrics’ executive committee on children and media.
"The central point is to not just talk about turning off the TV. It’s about changing the channel. The message to turn off the TV, frankly, falls on deaf ears," he said in an interview.
He likened the intervention to harm reduction, such as programs that distribute clean hypodermic needles to injection drug users in order to reduce the transmission of HIV.
The study randomized 820 children aged 3-5 years who were recruited from community pediatric practices and analyzed outcomes data on 276 in the intervention group and 289 in the control group. One of three case managers worked with parents in the intervention group to discuss the child’s media use and set goals (involving anything with a screen – TVs, DVDs, videos, and computers, for example). Every month for a year, the parents received phone calls for coaching, mailings of customized TV program guides geared toward the family’s available channels with recommended programs, a newsletter with tips and reinforcing messages, and in the first 6 months, DVDs with preview clips of suggested programs to pique the children’s interest.
The control group received the same number and amount of contacts, but these focused on nutrition, not screen viewing.
The effect sizes of the intervention were small but comparable to results of other studies that tried to change parenting practices or directly change children’s behaviors, he said. Subgroup analyses suggested that the media-diet intervention may have improved behavior scores in low-income boys more than in others.
Steering parents toward good media content is "something that pediatricians can do," perhaps with the help of resources like the reviews on CommonSenseMedia.org, Dr. Christakis suggested.
The New Zealand study followed a cohort of children born in 1972-1973, and compared child assessments at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, and 26 years with government data on criminal convictions through age 26 (Pediatrics 2013;131:439-46).
Those who watched more weekday television between ages 5 and 15 years were more likely to be among the 60 adults diagnosed with antisocial personality disorder at age 21 or 26, reported Ms. Robertson of the University of Otago (New Zealand). Among those who watched more than 3 hours per day, approximately 16% developed antisocial personality disorder, compared with approximately 9% of those who watched less than 2 hours per day.
Males were more likely than females to have a criminal conviction, but increased screen viewing raised the risk of conviction in both sexes. Approximately 35% of males and 12% of females who watched more than 3 hours per day ended up with criminal convictions, compared with approximately 19% of males and 3% of females who watched less than 2 hours per day.
The amount of TV viewing was not associated, however, with the likelihood of being convicted of a violent crime.
The study controlled for the effects of childhood socioeconomic status, IQ, early antisocial behavior, and level of parental control. The study did not track what kinds of programs were viewed.
The results were consistent with previous studies reporting an association between TV viewing and subsequent antisocial behavior, except for two studies that did not find these associations, Ms. Robertson noted. One was funded by the TV industry and excluded nearly a third of patients, potentially skewing the results, and the other had only a 1-year follow-up.
Dr. Christakis and Ms. Robertson reported having no financial disclosures. The teen study received funding support from the National Institutes of Health and grants from the National Institute of Mental Health and the William T. Grant Foundation. The preschool study was funded by a grant from the National Institute of Child Health and Human Development and NIH.
Reviewing the studies by Dr. Christakis and Ms. Robertson, Dr. Claire McCarthy couldn’t help thinking about Albert Einstein’s famous definition of insanity: doing the same thing over and over again and expecting a different result. Physicians have been advocating for years that children not watch TV more than 2 hours per day, yet U.S. children still watch 3-4 hours per day, on average. The message from physicians, however, largely hasn’t changed: "Turn it off."
"In the face of overwhelming evidence that the behavior is not changing, I am pretty sure that qualifies as insane," Dr. McCarthy wrote. "It is time to change our approach."
She lauded Dr. Christakis’s study as an example of how parental guidance could change. Physicians should switch the emphasis in their messages away from screen time and toward the effects of TV content "because it is the outcomes that matter," she said.
You don’t need to imply that watching TV all day is okay. Keep encouraging parents to shut off the TV and get children outside and playing. "But this cannot be all we do," she stressed. Physicians could find ways to help TV and video program creators add prosocial and other helpful content, not unlike efforts to get them to decrease cigarette smoking in movies.
"It is a variation on the ‘if you can’t beat ’em, join ’em’ idea," Dr. McCarthy wrote. "If the screens are going to be on, let’s concentrate on the content, and how we can make it work for children."
Dr. McCarthy is a pediatrician at Boston Children’s Hospital and is with Harvard Medical School, Boston. These comments were excerpted from her editorial published in the same issue as the two studies (Pediatrics 2013;131:589-90). She reported having no relevant financial disclosures.
Reviewing the studies by Dr. Christakis and Ms. Robertson, Dr. Claire McCarthy couldn’t help thinking about Albert Einstein’s famous definition of insanity: doing the same thing over and over again and expecting a different result. Physicians have been advocating for years that children not watch TV more than 2 hours per day, yet U.S. children still watch 3-4 hours per day, on average. The message from physicians, however, largely hasn’t changed: "Turn it off."
"In the face of overwhelming evidence that the behavior is not changing, I am pretty sure that qualifies as insane," Dr. McCarthy wrote. "It is time to change our approach."
She lauded Dr. Christakis’s study as an example of how parental guidance could change. Physicians should switch the emphasis in their messages away from screen time and toward the effects of TV content "because it is the outcomes that matter," she said.
You don’t need to imply that watching TV all day is okay. Keep encouraging parents to shut off the TV and get children outside and playing. "But this cannot be all we do," she stressed. Physicians could find ways to help TV and video program creators add prosocial and other helpful content, not unlike efforts to get them to decrease cigarette smoking in movies.
"It is a variation on the ‘if you can’t beat ’em, join ’em’ idea," Dr. McCarthy wrote. "If the screens are going to be on, let’s concentrate on the content, and how we can make it work for children."
Dr. McCarthy is a pediatrician at Boston Children’s Hospital and is with Harvard Medical School, Boston. These comments were excerpted from her editorial published in the same issue as the two studies (Pediatrics 2013;131:589-90). She reported having no relevant financial disclosures.
Reviewing the studies by Dr. Christakis and Ms. Robertson, Dr. Claire McCarthy couldn’t help thinking about Albert Einstein’s famous definition of insanity: doing the same thing over and over again and expecting a different result. Physicians have been advocating for years that children not watch TV more than 2 hours per day, yet U.S. children still watch 3-4 hours per day, on average. The message from physicians, however, largely hasn’t changed: "Turn it off."
"In the face of overwhelming evidence that the behavior is not changing, I am pretty sure that qualifies as insane," Dr. McCarthy wrote. "It is time to change our approach."
She lauded Dr. Christakis’s study as an example of how parental guidance could change. Physicians should switch the emphasis in their messages away from screen time and toward the effects of TV content "because it is the outcomes that matter," she said.
You don’t need to imply that watching TV all day is okay. Keep encouraging parents to shut off the TV and get children outside and playing. "But this cannot be all we do," she stressed. Physicians could find ways to help TV and video program creators add prosocial and other helpful content, not unlike efforts to get them to decrease cigarette smoking in movies.
"It is a variation on the ‘if you can’t beat ’em, join ’em’ idea," Dr. McCarthy wrote. "If the screens are going to be on, let’s concentrate on the content, and how we can make it work for children."
Dr. McCarthy is a pediatrician at Boston Children’s Hospital and is with Harvard Medical School, Boston. These comments were excerpted from her editorial published in the same issue as the two studies (Pediatrics 2013;131:589-90). She reported having no relevant financial disclosures.
Both the quantity and the content of television viewing by children may affect social behaviors long term, with effects that may last into adulthood, the results of two studies have shown.
In one randomized, controlled trial involving 565 preschool-aged children in the United States, coaching parents to reduce viewing of violence on the screen and to increase exposure to prosocial programming resulted in significantly less aggression and more prosocial behavior in the children after 6 months compared with the control group, effects that mostly were maintained at 12 months, Dr. Dmitri A. Christakis and his associates reported.
A separate longitudinal study from New Zealand followed 1,037 people from birth to age 26 years and found a significantly increased risk for antisocial outcomes in adults who had watched the most TV as children. Every extra hour of weeknight TV watching as children was associated with a 30% increase in the likelihood of having a criminal conviction by age 26, reported Lindsay A. Robertson and her associates.
Previous studies have shown that children imitate what they see on the screen and that reducing TV watching reduced aggression in 9-year-olds. Few studies have looked at preschoolers or at interventions aimed at content, Dr. Christakis said.
His study found that children fed a "media diet" deemphasizing violent programs and promoting viewing of programs that focus on sharing, caring, and education had Social Competence and Behavior Evaluation (SCBE) scores at 6 months that were 2 points better than in the control group, a significant difference that continued at 12 months (Pediatrics 2013;131:431-8).
The study did not try to change the amount of screen viewing, and both groups increased TV watching during the study, which often happens as children grow older. The likelihood of adults watching TV with their children did not differ between groups and remained stable throughout the study, despite efforts to promote coviewing, said Dr. Christakis, director of the center for child health, behavior, and development at Seattle Children’s Hospital and professor of pediatrics at the University of Washington, Seattle. He also is on the American Academy of Pediatrics’ executive committee on children and media.
"The central point is to not just talk about turning off the TV. It’s about changing the channel. The message to turn off the TV, frankly, falls on deaf ears," he said in an interview.
He likened the intervention to harm reduction, such as programs that distribute clean hypodermic needles to injection drug users in order to reduce the transmission of HIV.
The study randomized 820 children aged 3-5 years who were recruited from community pediatric practices and analyzed outcomes data on 276 in the intervention group and 289 in the control group. One of three case managers worked with parents in the intervention group to discuss the child’s media use and set goals (involving anything with a screen – TVs, DVDs, videos, and computers, for example). Every month for a year, the parents received phone calls for coaching, mailings of customized TV program guides geared toward the family’s available channels with recommended programs, a newsletter with tips and reinforcing messages, and in the first 6 months, DVDs with preview clips of suggested programs to pique the children’s interest.
The control group received the same number and amount of contacts, but these focused on nutrition, not screen viewing.
The effect sizes of the intervention were small but comparable to results of other studies that tried to change parenting practices or directly change children’s behaviors, he said. Subgroup analyses suggested that the media-diet intervention may have improved behavior scores in low-income boys more than in others.
Steering parents toward good media content is "something that pediatricians can do," perhaps with the help of resources like the reviews on CommonSenseMedia.org, Dr. Christakis suggested.
The New Zealand study followed a cohort of children born in 1972-1973, and compared child assessments at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, and 26 years with government data on criminal convictions through age 26 (Pediatrics 2013;131:439-46).
Those who watched more weekday television between ages 5 and 15 years were more likely to be among the 60 adults diagnosed with antisocial personality disorder at age 21 or 26, reported Ms. Robertson of the University of Otago (New Zealand). Among those who watched more than 3 hours per day, approximately 16% developed antisocial personality disorder, compared with approximately 9% of those who watched less than 2 hours per day.
Males were more likely than females to have a criminal conviction, but increased screen viewing raised the risk of conviction in both sexes. Approximately 35% of males and 12% of females who watched more than 3 hours per day ended up with criminal convictions, compared with approximately 19% of males and 3% of females who watched less than 2 hours per day.
The amount of TV viewing was not associated, however, with the likelihood of being convicted of a violent crime.
The study controlled for the effects of childhood socioeconomic status, IQ, early antisocial behavior, and level of parental control. The study did not track what kinds of programs were viewed.
The results were consistent with previous studies reporting an association between TV viewing and subsequent antisocial behavior, except for two studies that did not find these associations, Ms. Robertson noted. One was funded by the TV industry and excluded nearly a third of patients, potentially skewing the results, and the other had only a 1-year follow-up.
Dr. Christakis and Ms. Robertson reported having no financial disclosures. The teen study received funding support from the National Institutes of Health and grants from the National Institute of Mental Health and the William T. Grant Foundation. The preschool study was funded by a grant from the National Institute of Child Health and Human Development and NIH.
Both the quantity and the content of television viewing by children may affect social behaviors long term, with effects that may last into adulthood, the results of two studies have shown.
In one randomized, controlled trial involving 565 preschool-aged children in the United States, coaching parents to reduce viewing of violence on the screen and to increase exposure to prosocial programming resulted in significantly less aggression and more prosocial behavior in the children after 6 months compared with the control group, effects that mostly were maintained at 12 months, Dr. Dmitri A. Christakis and his associates reported.
A separate longitudinal study from New Zealand followed 1,037 people from birth to age 26 years and found a significantly increased risk for antisocial outcomes in adults who had watched the most TV as children. Every extra hour of weeknight TV watching as children was associated with a 30% increase in the likelihood of having a criminal conviction by age 26, reported Lindsay A. Robertson and her associates.
Previous studies have shown that children imitate what they see on the screen and that reducing TV watching reduced aggression in 9-year-olds. Few studies have looked at preschoolers or at interventions aimed at content, Dr. Christakis said.
His study found that children fed a "media diet" deemphasizing violent programs and promoting viewing of programs that focus on sharing, caring, and education had Social Competence and Behavior Evaluation (SCBE) scores at 6 months that were 2 points better than in the control group, a significant difference that continued at 12 months (Pediatrics 2013;131:431-8).
The study did not try to change the amount of screen viewing, and both groups increased TV watching during the study, which often happens as children grow older. The likelihood of adults watching TV with their children did not differ between groups and remained stable throughout the study, despite efforts to promote coviewing, said Dr. Christakis, director of the center for child health, behavior, and development at Seattle Children’s Hospital and professor of pediatrics at the University of Washington, Seattle. He also is on the American Academy of Pediatrics’ executive committee on children and media.
"The central point is to not just talk about turning off the TV. It’s about changing the channel. The message to turn off the TV, frankly, falls on deaf ears," he said in an interview.
He likened the intervention to harm reduction, such as programs that distribute clean hypodermic needles to injection drug users in order to reduce the transmission of HIV.
The study randomized 820 children aged 3-5 years who were recruited from community pediatric practices and analyzed outcomes data on 276 in the intervention group and 289 in the control group. One of three case managers worked with parents in the intervention group to discuss the child’s media use and set goals (involving anything with a screen – TVs, DVDs, videos, and computers, for example). Every month for a year, the parents received phone calls for coaching, mailings of customized TV program guides geared toward the family’s available channels with recommended programs, a newsletter with tips and reinforcing messages, and in the first 6 months, DVDs with preview clips of suggested programs to pique the children’s interest.
The control group received the same number and amount of contacts, but these focused on nutrition, not screen viewing.
The effect sizes of the intervention were small but comparable to results of other studies that tried to change parenting practices or directly change children’s behaviors, he said. Subgroup analyses suggested that the media-diet intervention may have improved behavior scores in low-income boys more than in others.
Steering parents toward good media content is "something that pediatricians can do," perhaps with the help of resources like the reviews on CommonSenseMedia.org, Dr. Christakis suggested.
The New Zealand study followed a cohort of children born in 1972-1973, and compared child assessments at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, and 26 years with government data on criminal convictions through age 26 (Pediatrics 2013;131:439-46).
Those who watched more weekday television between ages 5 and 15 years were more likely to be among the 60 adults diagnosed with antisocial personality disorder at age 21 or 26, reported Ms. Robertson of the University of Otago (New Zealand). Among those who watched more than 3 hours per day, approximately 16% developed antisocial personality disorder, compared with approximately 9% of those who watched less than 2 hours per day.
Males were more likely than females to have a criminal conviction, but increased screen viewing raised the risk of conviction in both sexes. Approximately 35% of males and 12% of females who watched more than 3 hours per day ended up with criminal convictions, compared with approximately 19% of males and 3% of females who watched less than 2 hours per day.
The amount of TV viewing was not associated, however, with the likelihood of being convicted of a violent crime.
The study controlled for the effects of childhood socioeconomic status, IQ, early antisocial behavior, and level of parental control. The study did not track what kinds of programs were viewed.
The results were consistent with previous studies reporting an association between TV viewing and subsequent antisocial behavior, except for two studies that did not find these associations, Ms. Robertson noted. One was funded by the TV industry and excluded nearly a third of patients, potentially skewing the results, and the other had only a 1-year follow-up.
Dr. Christakis and Ms. Robertson reported having no financial disclosures. The teen study received funding support from the National Institutes of Health and grants from the National Institute of Mental Health and the William T. Grant Foundation. The preschool study was funded by a grant from the National Institute of Child Health and Human Development and NIH.
FROM PEDIATRICS
Major Finding: Coaching parents to steer children’s TV viewing toward prosocial programs led to a significant, 2-point better score on the Social Competence and Behavior Evaluation at 6 and 12 months, compared with a control group. A separate study found a 30% increased risk for adult criminal conviction for every hour of TV viewing on weekdays from ages 5-15 years.
Data Source: A prospective, randomized, controlled trial of a "media diet" in 565 preschool-aged U.S. children, and a prospective longitudinal study of 1,037 New Zealanders from birth to age 26 years.
Disclosures: Dr. Christakis and Ms. Robertson reported having no relevant financial disclosures. The teen study received funding support from the National Institutes of Health and grants from the National Institute of Mental Health and the William T. Grant Foundation. The preschool study was funded by a grant from the National Institute of Child Health and Human Development and NIH.
Racial gap in gastric cancer survival narrows at 3 years
Race is a significant predictor of the odds of surviving gastric cancer at the time of diagnosis: Its impact lessens the longer the patient survives, an analysis of data on 24,657 patients who underwent potentially curative surgery suggests.
At the time of diagnosis, estimates of 3-year relative conditional survival rates were significantly different by race. Asian patients (17% of the cohort) had a 3-year relative conditional survival of 52%, compared with 42% for black patients (14% of the cohort), and 41% for white patients (69% of the cohort), Dr. David T. Luyimbazi and his associates reported.
For patients who were still alive 3 years after diagnosis, the estimates that they would survive another 3 years improved in each group, and the racial gap narrowed significantly and nearly disappeared. Three-year relative conditional survival rates were 83% for Asian patients, 82% for black patients, and 78% for white patients, Dr. Luyimbazi said in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
His study won a Merit Award at the meeting.
The investigators analyzed data from the Surveillance, Epidemiology and End Results (SEER) registry on patients with gastric cancer who were treated with curative surgery from 1988 to 2006.
Conditional survival analyses estimate a patient’s probability of surviving for a specified time given that the patient already has survived a specified time after diagnosis. In patients with gastric cancer, conditional survival estimates rely on disease staging, pathological tumor characteristics, and a variety of clinical factors. These estimates do not typically include the influence of racial disparities, even though previous studies have shown that racial disparities are a predictor of survival, independent of clinical or pathological features, said Dr. Luyimbazi, a surgical oncology fellow at City of Hope National Medical Center, Duarte, Calif.
Conditional survival can be a "confusing concept" but it’s gradually being embraced by oncologists because it makes sense that a patient’s prognosis at the time of diagnosis is not the same after the patient has survived a year or 2 or 3 years longer, he said in an interview.
Eventually, it may be possible to create a nomogram so that physicians can use a particular patient’s characteristics to estimate how much longer the patient might live, given how long the that person has lived since diagnosis, he suggested. A clinician might be able to suggest to a patient who has been followed every 6 months for the last 3 years that follow-up intervals be lengthened or shortened, depending on any change in conditional survival, Dr. Luyimbazi said. And if a patient reaches a point at which the estimated conditional survival is the same as it was before being diagnosed with cancer, the patient might revert to the same surveillance schedules used for the general population.
Conditional survival was reported in the study as a relative conditional survival rate, which is the observed conditional survival rate divided by the expected conditional survival rate from a general population that is matched to the study cohort by age, sex, and race.
One year after diagnosis, the 3-year relative conditional survival rates increased to 64% for Asian patients, 56% for black patients, and 55% for white patients. By 2 years after diagnosis, the 3-year relative conditional survival rates were 76% for Asian patients, 71% for black patients, and 68% for white patients. Rates improved further, and the racial gap narrowed even more, by the third year after diagnosis.
Dr. Luyimbazi reported having no financial disclosures.
On Twitter @sherryboschert
Race is a significant predictor of the odds of surviving gastric cancer at the time of diagnosis: Its impact lessens the longer the patient survives, an analysis of data on 24,657 patients who underwent potentially curative surgery suggests.
At the time of diagnosis, estimates of 3-year relative conditional survival rates were significantly different by race. Asian patients (17% of the cohort) had a 3-year relative conditional survival of 52%, compared with 42% for black patients (14% of the cohort), and 41% for white patients (69% of the cohort), Dr. David T. Luyimbazi and his associates reported.
For patients who were still alive 3 years after diagnosis, the estimates that they would survive another 3 years improved in each group, and the racial gap narrowed significantly and nearly disappeared. Three-year relative conditional survival rates were 83% for Asian patients, 82% for black patients, and 78% for white patients, Dr. Luyimbazi said in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
His study won a Merit Award at the meeting.
The investigators analyzed data from the Surveillance, Epidemiology and End Results (SEER) registry on patients with gastric cancer who were treated with curative surgery from 1988 to 2006.
Conditional survival analyses estimate a patient’s probability of surviving for a specified time given that the patient already has survived a specified time after diagnosis. In patients with gastric cancer, conditional survival estimates rely on disease staging, pathological tumor characteristics, and a variety of clinical factors. These estimates do not typically include the influence of racial disparities, even though previous studies have shown that racial disparities are a predictor of survival, independent of clinical or pathological features, said Dr. Luyimbazi, a surgical oncology fellow at City of Hope National Medical Center, Duarte, Calif.
Conditional survival can be a "confusing concept" but it’s gradually being embraced by oncologists because it makes sense that a patient’s prognosis at the time of diagnosis is not the same after the patient has survived a year or 2 or 3 years longer, he said in an interview.
Eventually, it may be possible to create a nomogram so that physicians can use a particular patient’s characteristics to estimate how much longer the patient might live, given how long the that person has lived since diagnosis, he suggested. A clinician might be able to suggest to a patient who has been followed every 6 months for the last 3 years that follow-up intervals be lengthened or shortened, depending on any change in conditional survival, Dr. Luyimbazi said. And if a patient reaches a point at which the estimated conditional survival is the same as it was before being diagnosed with cancer, the patient might revert to the same surveillance schedules used for the general population.
Conditional survival was reported in the study as a relative conditional survival rate, which is the observed conditional survival rate divided by the expected conditional survival rate from a general population that is matched to the study cohort by age, sex, and race.
One year after diagnosis, the 3-year relative conditional survival rates increased to 64% for Asian patients, 56% for black patients, and 55% for white patients. By 2 years after diagnosis, the 3-year relative conditional survival rates were 76% for Asian patients, 71% for black patients, and 68% for white patients. Rates improved further, and the racial gap narrowed even more, by the third year after diagnosis.
Dr. Luyimbazi reported having no financial disclosures.
On Twitter @sherryboschert
Race is a significant predictor of the odds of surviving gastric cancer at the time of diagnosis: Its impact lessens the longer the patient survives, an analysis of data on 24,657 patients who underwent potentially curative surgery suggests.
At the time of diagnosis, estimates of 3-year relative conditional survival rates were significantly different by race. Asian patients (17% of the cohort) had a 3-year relative conditional survival of 52%, compared with 42% for black patients (14% of the cohort), and 41% for white patients (69% of the cohort), Dr. David T. Luyimbazi and his associates reported.
For patients who were still alive 3 years after diagnosis, the estimates that they would survive another 3 years improved in each group, and the racial gap narrowed significantly and nearly disappeared. Three-year relative conditional survival rates were 83% for Asian patients, 82% for black patients, and 78% for white patients, Dr. Luyimbazi said in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
His study won a Merit Award at the meeting.
The investigators analyzed data from the Surveillance, Epidemiology and End Results (SEER) registry on patients with gastric cancer who were treated with curative surgery from 1988 to 2006.
Conditional survival analyses estimate a patient’s probability of surviving for a specified time given that the patient already has survived a specified time after diagnosis. In patients with gastric cancer, conditional survival estimates rely on disease staging, pathological tumor characteristics, and a variety of clinical factors. These estimates do not typically include the influence of racial disparities, even though previous studies have shown that racial disparities are a predictor of survival, independent of clinical or pathological features, said Dr. Luyimbazi, a surgical oncology fellow at City of Hope National Medical Center, Duarte, Calif.
Conditional survival can be a "confusing concept" but it’s gradually being embraced by oncologists because it makes sense that a patient’s prognosis at the time of diagnosis is not the same after the patient has survived a year or 2 or 3 years longer, he said in an interview.
Eventually, it may be possible to create a nomogram so that physicians can use a particular patient’s characteristics to estimate how much longer the patient might live, given how long the that person has lived since diagnosis, he suggested. A clinician might be able to suggest to a patient who has been followed every 6 months for the last 3 years that follow-up intervals be lengthened or shortened, depending on any change in conditional survival, Dr. Luyimbazi said. And if a patient reaches a point at which the estimated conditional survival is the same as it was before being diagnosed with cancer, the patient might revert to the same surveillance schedules used for the general population.
Conditional survival was reported in the study as a relative conditional survival rate, which is the observed conditional survival rate divided by the expected conditional survival rate from a general population that is matched to the study cohort by age, sex, and race.
One year after diagnosis, the 3-year relative conditional survival rates increased to 64% for Asian patients, 56% for black patients, and 55% for white patients. By 2 years after diagnosis, the 3-year relative conditional survival rates were 76% for Asian patients, 71% for black patients, and 68% for white patients. Rates improved further, and the racial gap narrowed even more, by the third year after diagnosis.
Dr. Luyimbazi reported having no financial disclosures.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Three-year relative conditional survival rates for Asian, black, or white patients with gastric cancer who underwent curative surgery improved from 52%, 42%, and 41% at baseline, respectively, to 83%, 82% and 78%, respectively, 3 years later.
Data Source: Retrospective analysis of SEER registry data on 24,657 patients with gastric cancer treated with potentially curative surgery.
Disclosures: Dr. Luyimbazi reported having no financial disclosures.
Capecitabine chemoradiotherapy effective in local pancreatic cancer
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Median progression-free survival after 9 months of follow-up was 12 months in 35 patients given capecitabine plus radiotherapy after induction chemotherapy and 10.4 months in patients given gemcitabine plus radiotherapy following induction chemotherapy.
Data Source: A multicenter trial that randomized 74 patients with locally advanced pancreatic cancer.
Disclosures: Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Roche, or Sanofi.
Survival shorter in young gastric cancer patients
Patients with gastric adenocarcinoma who were diagnosed before age 40 years died significantly sooner than did older patients, based on the results of a single-center, retrospective study of 520 cases.
Patients diagnosed before age 40 survived a median of 5 months after diagnosis; 24% were alive at 1 year. Older patients survived a median of 8 months, and 39% were alive at 1 year, reported Dr. Bryan Goldner and his associates.
Surgical exploration was often futile in the younger patients, said Dr. Goldner of Harbor-UCLA Medical Center in Torrance, Calif. Surgery removed all tumors with histologically free margins (R0 resection) in 33% of younger patients, compared with 60% of older patients, he reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Recent reports in the medical literature suggest that younger patients with gastric adenocarcinoma are more likely to be diagnosed with node-positive and metastatic disease. One retrospective study of 350 patients found that younger patients had more aggressive gastric adenocarcinomas and died sooner than older patients (Arch. Surg. 2009;144:506-10).
A separate retrospective study of 33,236 U.S. patients found that younger patients presented with more advanced gastric adenocarcinoma but had better survival outcomes than older patients when stratified by disease stage (Ann. Surg. Oncol. 2011;18:2800-7).
Gastric cancer might not be suspected in younger patients, which could result in young patients going undiagnosed until their cancers are more advanced, Dr. Goldner suggested.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Goldner reported having no financial disclosures.
On Twitter @sherryboschert
Patients with gastric adenocarcinoma who were diagnosed before age 40 years died significantly sooner than did older patients, based on the results of a single-center, retrospective study of 520 cases.
Patients diagnosed before age 40 survived a median of 5 months after diagnosis; 24% were alive at 1 year. Older patients survived a median of 8 months, and 39% were alive at 1 year, reported Dr. Bryan Goldner and his associates.
Surgical exploration was often futile in the younger patients, said Dr. Goldner of Harbor-UCLA Medical Center in Torrance, Calif. Surgery removed all tumors with histologically free margins (R0 resection) in 33% of younger patients, compared with 60% of older patients, he reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Recent reports in the medical literature suggest that younger patients with gastric adenocarcinoma are more likely to be diagnosed with node-positive and metastatic disease. One retrospective study of 350 patients found that younger patients had more aggressive gastric adenocarcinomas and died sooner than older patients (Arch. Surg. 2009;144:506-10).
A separate retrospective study of 33,236 U.S. patients found that younger patients presented with more advanced gastric adenocarcinoma but had better survival outcomes than older patients when stratified by disease stage (Ann. Surg. Oncol. 2011;18:2800-7).
Gastric cancer might not be suspected in younger patients, which could result in young patients going undiagnosed until their cancers are more advanced, Dr. Goldner suggested.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Goldner reported having no financial disclosures.
On Twitter @sherryboschert
Patients with gastric adenocarcinoma who were diagnosed before age 40 years died significantly sooner than did older patients, based on the results of a single-center, retrospective study of 520 cases.
Patients diagnosed before age 40 survived a median of 5 months after diagnosis; 24% were alive at 1 year. Older patients survived a median of 8 months, and 39% were alive at 1 year, reported Dr. Bryan Goldner and his associates.
Surgical exploration was often futile in the younger patients, said Dr. Goldner of Harbor-UCLA Medical Center in Torrance, Calif. Surgery removed all tumors with histologically free margins (R0 resection) in 33% of younger patients, compared with 60% of older patients, he reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Recent reports in the medical literature suggest that younger patients with gastric adenocarcinoma are more likely to be diagnosed with node-positive and metastatic disease. One retrospective study of 350 patients found that younger patients had more aggressive gastric adenocarcinomas and died sooner than older patients (Arch. Surg. 2009;144:506-10).
A separate retrospective study of 33,236 U.S. patients found that younger patients presented with more advanced gastric adenocarcinoma but had better survival outcomes than older patients when stratified by disease stage (Ann. Surg. Oncol. 2011;18:2800-7).
Gastric cancer might not be suspected in younger patients, which could result in young patients going undiagnosed until their cancers are more advanced, Dr. Goldner suggested.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Goldner reported having no financial disclosures.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Patients diagnosed with gastric adenocarcinoma before age 40 years lived a median of 5 months; older patients lived a median of 8 months.
Data Source: Retrospective study of 520 patients with gastric cancer at one public hospital.
Disclosures: Dr. Goldner reported having no financial disclosures.
Gene profiling predicted responses to colorectal, pancreatic cancer treatment
SAN FRANCISCO – Gene expression profiling of patients with colorectal cancer and pharmacogenomic modeling of patients with pancreatic cancer could help identify which patients will respond to particular chemotherapies, preliminary evidence from two small studies suggests.
Spanish investigators developed a molecular classification system using gene expression data from 188 patients with colorectal cancer to identify three subtypes of the cancer, which they called subtypes A, B and C. They then performed a multicenter validation study using tumor samples from 543 patients with stage II and III colorectal cancer, and classified 35% of samples as subtype A, 50% as subtype B, and 15% as subtype C.
They found that the different subtypes were associated with different clinical and biological characteristics and helped predict response to adjuvant chemotherapy regimens based on 5-fluorouracil (5-FU) when compared with 10 years of patient records, Dr. Josep Tabernero and his associates reported at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.
Patients with subtype C colorectal cancer had a mesenchymal gene expression phenotype and did not respond to 5-FU–based chemotherapy, suggesting that new, targeted treatments need to be found for these tumors, said Dr. Tabernero, director of clinical research at Vall d’Hebron Institute of Oncology, Barcelona.
Patients with subtype A colorectal cancer had the best prognosis – "some of them don’t even need adjuvant therapy," he said in a separate press briefing – and did respond to 5-FU–based chemotherapy. Patients with subtype B had a poor prognosis but showed an even more dramatic response to adjuvant chemotherapy.
Subtypes A and B had more proliferative and epithelial phenotypes than did subtype C. Tumors in subtype B showed a low frequency of overall kinase mutation, compared with subtype A or C.
Dr. Tabernero’s gene expression research follows previous work by others who successfully used gene expression patterns in breast cancer to create molecular subtypes that have been associated with prognosis and used to help create treatment plans. In colorectal cancer, previously only KRAS gene status has been shown to be a predictor of response to treatment focusing on epidermal growth factor receptor activity in advanced disease, he added.
A separate study is underway to validate the molecular subtype classification system in patients with stage IV colorectal cancer.
Dr. Kenneth H. Yu and his associates reported preliminary results of an ongoing, separate study that suggests pharmacogenomic profiling of 20 patients with nonresectable pancreatic adenocarcinomas predicted who would, or would not, respond to first-line chemotherapy.
The study so far has enrolled 50 patients with stage II-IV pancreatic adenocarcinoma who get blood samples taken before starting 1 of 12 different drug combinations chosen by their physician for first-line chemotherapy. If the tumor progresses on first-line treatment, another blood sample is taken before starting second-line chemotherapy. The blood is analyzed for pharmacogenomic characteristics in circulating tumor cells and invasive cells that might predict response or resistance to treatment.
The scientists analyzing the blood samples are blinded to treatment choices, and the treating physicians are blinded to the pharmacogenomic profile results of the blood samples, noted Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
Twenty patients so far have had the two blood samples. Using a pharmacogenomic model created in laboratory work by CellPath Therapeutics, the investigators predicted that tumors in six patients would be sensitive to the first-line treatment received, six other patients in an intermediate group were predicted to have some response to the first-line treatment, and tumors in eight patients were predicted to be resistant to the first-line treatments received.
The median time to tumor progression supported these classifications – 7.3 months in the sensitive group, 5.3 months in the intermediate group, and 3.7 months in the resistant group, Dr. Yu reported.
Analyses of gene pathways seem to have identified other predictors of treatment response. "Genes do not exist in isolation. The proteins these genes encode interact with each other in pathways – you can think of them as networks of genes and gene products. Changes in one gene along the pathway can affect other genes," he said in a separate press briefing.
A longer response to treatment was seen in patients with disruptions in the pathway called E2F1, which is known for regulating cell division. A shorter response to treatment was seen in patients who had disruptions in the NFkB pathway, which has been implicated in regulating cell division and cell survival, particularly in cancer. The investigators also found disruptions in the phospholipase C and retinoblastoma 1 pathways when tumors became resistant to treatment.
"Pharmacogenetic profiling is a promising and exploratory tool for predicting treatment response in pancreatic cancer," Dr. Yu said. The validation study continues, and future validation studies are planned.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
These two studies "highlight the direction that the field of oncology is going, both in terms of research and practice. The notion being that tumors that look the same under the microscope – colon cancers, for example – at the level of their molecular makeup may actually fit into several different categories that all look the same to a pathologist. We’re starting to use these categorizations based on the genetic makeup, the profile, and of what genes are turned on and off to help us make treatment decisions about which drugs might work best against which particular tumors, and which drugs might not work at all," Dr. Neal J. Meropol said.
The studies look at different ways of profiling tumors and tumor cells that ultimately could help guide treatment by predicting which tumors will respond to chemotherapy and which are likely to develop resistance.
Dr. Yu’s study of pharmacogenetic modeling "shows that it’s possible using a noninvasive methodology – simply a blood sample – to identify tumor cells and to characterize them at the molecular level. This is important, first of all, because it doesn’t require another biopsy of a patient’s tumor, which would be more invasive," Dr. Meropol said. "But, also, we know that when a tumor that initially responds to treatment starts to grow again, it has acquired new mutations, new characteristics that make it resistant to the therapy that it once responded to. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time."
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
These two studies "highlight the direction that the field of oncology is going, both in terms of research and practice. The notion being that tumors that look the same under the microscope – colon cancers, for example – at the level of their molecular makeup may actually fit into several different categories that all look the same to a pathologist. We’re starting to use these categorizations based on the genetic makeup, the profile, and of what genes are turned on and off to help us make treatment decisions about which drugs might work best against which particular tumors, and which drugs might not work at all," Dr. Neal J. Meropol said.
The studies look at different ways of profiling tumors and tumor cells that ultimately could help guide treatment by predicting which tumors will respond to chemotherapy and which are likely to develop resistance.
Dr. Yu’s study of pharmacogenetic modeling "shows that it’s possible using a noninvasive methodology – simply a blood sample – to identify tumor cells and to characterize them at the molecular level. This is important, first of all, because it doesn’t require another biopsy of a patient’s tumor, which would be more invasive," Dr. Meropol said. "But, also, we know that when a tumor that initially responds to treatment starts to grow again, it has acquired new mutations, new characteristics that make it resistant to the therapy that it once responded to. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time."
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
These two studies "highlight the direction that the field of oncology is going, both in terms of research and practice. The notion being that tumors that look the same under the microscope – colon cancers, for example – at the level of their molecular makeup may actually fit into several different categories that all look the same to a pathologist. We’re starting to use these categorizations based on the genetic makeup, the profile, and of what genes are turned on and off to help us make treatment decisions about which drugs might work best against which particular tumors, and which drugs might not work at all," Dr. Neal J. Meropol said.
The studies look at different ways of profiling tumors and tumor cells that ultimately could help guide treatment by predicting which tumors will respond to chemotherapy and which are likely to develop resistance.
Dr. Yu’s study of pharmacogenetic modeling "shows that it’s possible using a noninvasive methodology – simply a blood sample – to identify tumor cells and to characterize them at the molecular level. This is important, first of all, because it doesn’t require another biopsy of a patient’s tumor, which would be more invasive," Dr. Meropol said. "But, also, we know that when a tumor that initially responds to treatment starts to grow again, it has acquired new mutations, new characteristics that make it resistant to the therapy that it once responded to. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time."
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
SAN FRANCISCO – Gene expression profiling of patients with colorectal cancer and pharmacogenomic modeling of patients with pancreatic cancer could help identify which patients will respond to particular chemotherapies, preliminary evidence from two small studies suggests.
Spanish investigators developed a molecular classification system using gene expression data from 188 patients with colorectal cancer to identify three subtypes of the cancer, which they called subtypes A, B and C. They then performed a multicenter validation study using tumor samples from 543 patients with stage II and III colorectal cancer, and classified 35% of samples as subtype A, 50% as subtype B, and 15% as subtype C.
They found that the different subtypes were associated with different clinical and biological characteristics and helped predict response to adjuvant chemotherapy regimens based on 5-fluorouracil (5-FU) when compared with 10 years of patient records, Dr. Josep Tabernero and his associates reported at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.
Patients with subtype C colorectal cancer had a mesenchymal gene expression phenotype and did not respond to 5-FU–based chemotherapy, suggesting that new, targeted treatments need to be found for these tumors, said Dr. Tabernero, director of clinical research at Vall d’Hebron Institute of Oncology, Barcelona.
Patients with subtype A colorectal cancer had the best prognosis – "some of them don’t even need adjuvant therapy," he said in a separate press briefing – and did respond to 5-FU–based chemotherapy. Patients with subtype B had a poor prognosis but showed an even more dramatic response to adjuvant chemotherapy.
Subtypes A and B had more proliferative and epithelial phenotypes than did subtype C. Tumors in subtype B showed a low frequency of overall kinase mutation, compared with subtype A or C.
Dr. Tabernero’s gene expression research follows previous work by others who successfully used gene expression patterns in breast cancer to create molecular subtypes that have been associated with prognosis and used to help create treatment plans. In colorectal cancer, previously only KRAS gene status has been shown to be a predictor of response to treatment focusing on epidermal growth factor receptor activity in advanced disease, he added.
A separate study is underway to validate the molecular subtype classification system in patients with stage IV colorectal cancer.
Dr. Kenneth H. Yu and his associates reported preliminary results of an ongoing, separate study that suggests pharmacogenomic profiling of 20 patients with nonresectable pancreatic adenocarcinomas predicted who would, or would not, respond to first-line chemotherapy.
The study so far has enrolled 50 patients with stage II-IV pancreatic adenocarcinoma who get blood samples taken before starting 1 of 12 different drug combinations chosen by their physician for first-line chemotherapy. If the tumor progresses on first-line treatment, another blood sample is taken before starting second-line chemotherapy. The blood is analyzed for pharmacogenomic characteristics in circulating tumor cells and invasive cells that might predict response or resistance to treatment.
The scientists analyzing the blood samples are blinded to treatment choices, and the treating physicians are blinded to the pharmacogenomic profile results of the blood samples, noted Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
Twenty patients so far have had the two blood samples. Using a pharmacogenomic model created in laboratory work by CellPath Therapeutics, the investigators predicted that tumors in six patients would be sensitive to the first-line treatment received, six other patients in an intermediate group were predicted to have some response to the first-line treatment, and tumors in eight patients were predicted to be resistant to the first-line treatments received.
The median time to tumor progression supported these classifications – 7.3 months in the sensitive group, 5.3 months in the intermediate group, and 3.7 months in the resistant group, Dr. Yu reported.
Analyses of gene pathways seem to have identified other predictors of treatment response. "Genes do not exist in isolation. The proteins these genes encode interact with each other in pathways – you can think of them as networks of genes and gene products. Changes in one gene along the pathway can affect other genes," he said in a separate press briefing.
A longer response to treatment was seen in patients with disruptions in the pathway called E2F1, which is known for regulating cell division. A shorter response to treatment was seen in patients who had disruptions in the NFkB pathway, which has been implicated in regulating cell division and cell survival, particularly in cancer. The investigators also found disruptions in the phospholipase C and retinoblastoma 1 pathways when tumors became resistant to treatment.
"Pharmacogenetic profiling is a promising and exploratory tool for predicting treatment response in pancreatic cancer," Dr. Yu said. The validation study continues, and future validation studies are planned.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
SAN FRANCISCO – Gene expression profiling of patients with colorectal cancer and pharmacogenomic modeling of patients with pancreatic cancer could help identify which patients will respond to particular chemotherapies, preliminary evidence from two small studies suggests.
Spanish investigators developed a molecular classification system using gene expression data from 188 patients with colorectal cancer to identify three subtypes of the cancer, which they called subtypes A, B and C. They then performed a multicenter validation study using tumor samples from 543 patients with stage II and III colorectal cancer, and classified 35% of samples as subtype A, 50% as subtype B, and 15% as subtype C.
They found that the different subtypes were associated with different clinical and biological characteristics and helped predict response to adjuvant chemotherapy regimens based on 5-fluorouracil (5-FU) when compared with 10 years of patient records, Dr. Josep Tabernero and his associates reported at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.
Patients with subtype C colorectal cancer had a mesenchymal gene expression phenotype and did not respond to 5-FU–based chemotherapy, suggesting that new, targeted treatments need to be found for these tumors, said Dr. Tabernero, director of clinical research at Vall d’Hebron Institute of Oncology, Barcelona.
Patients with subtype A colorectal cancer had the best prognosis – "some of them don’t even need adjuvant therapy," he said in a separate press briefing – and did respond to 5-FU–based chemotherapy. Patients with subtype B had a poor prognosis but showed an even more dramatic response to adjuvant chemotherapy.
Subtypes A and B had more proliferative and epithelial phenotypes than did subtype C. Tumors in subtype B showed a low frequency of overall kinase mutation, compared with subtype A or C.
Dr. Tabernero’s gene expression research follows previous work by others who successfully used gene expression patterns in breast cancer to create molecular subtypes that have been associated with prognosis and used to help create treatment plans. In colorectal cancer, previously only KRAS gene status has been shown to be a predictor of response to treatment focusing on epidermal growth factor receptor activity in advanced disease, he added.
A separate study is underway to validate the molecular subtype classification system in patients with stage IV colorectal cancer.
Dr. Kenneth H. Yu and his associates reported preliminary results of an ongoing, separate study that suggests pharmacogenomic profiling of 20 patients with nonresectable pancreatic adenocarcinomas predicted who would, or would not, respond to first-line chemotherapy.
The study so far has enrolled 50 patients with stage II-IV pancreatic adenocarcinoma who get blood samples taken before starting 1 of 12 different drug combinations chosen by their physician for first-line chemotherapy. If the tumor progresses on first-line treatment, another blood sample is taken before starting second-line chemotherapy. The blood is analyzed for pharmacogenomic characteristics in circulating tumor cells and invasive cells that might predict response or resistance to treatment.
The scientists analyzing the blood samples are blinded to treatment choices, and the treating physicians are blinded to the pharmacogenomic profile results of the blood samples, noted Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
Twenty patients so far have had the two blood samples. Using a pharmacogenomic model created in laboratory work by CellPath Therapeutics, the investigators predicted that tumors in six patients would be sensitive to the first-line treatment received, six other patients in an intermediate group were predicted to have some response to the first-line treatment, and tumors in eight patients were predicted to be resistant to the first-line treatments received.
The median time to tumor progression supported these classifications – 7.3 months in the sensitive group, 5.3 months in the intermediate group, and 3.7 months in the resistant group, Dr. Yu reported.
Analyses of gene pathways seem to have identified other predictors of treatment response. "Genes do not exist in isolation. The proteins these genes encode interact with each other in pathways – you can think of them as networks of genes and gene products. Changes in one gene along the pathway can affect other genes," he said in a separate press briefing.
A longer response to treatment was seen in patients with disruptions in the pathway called E2F1, which is known for regulating cell division. A shorter response to treatment was seen in patients who had disruptions in the NFkB pathway, which has been implicated in regulating cell division and cell survival, particularly in cancer. The investigators also found disruptions in the phospholipase C and retinoblastoma 1 pathways when tumors became resistant to treatment.
"Pharmacogenetic profiling is a promising and exploratory tool for predicting treatment response in pancreatic cancer," Dr. Yu said. The validation study continues, and future validation studies are planned.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
AT ASCO'S GASTROINTESTINAL CANCERS SYMPOSIUM
Major finding: Gene expression patterns identified three subtypes of stage II or III colorectal cancer with different responses to 5-FU–based adjuvant chemotherapy. Pharmacogenomic profiling predicted which patients with pancreatic cancer would respond to, have intermediate sensitivity, or fail first-line chemotherapy.
Data source: Prospective validation of colorectal cancer subtyping and treatment response in gene expression analysis of tumors in 385 patients, compared with records on 10 years of follow-up, and preliminary results of pharmacogenomic profiling in 20 of 50 patients with unresectable pancreatic adenocarcinoma.
Disclosures: One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
Japanese study: S-1 adjuvant chemo improved pancreatic cancer survival
SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.
S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).
The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.
Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.
The study is ongoing; a final analysis is planned after 240 deaths.
S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."
Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.
Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.
Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.
Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.
In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.
On Twitter @SherryBoschert
To put this into perspective, pancreatic cancer worldwide remains a highly lethal disease, yet about a third of patients who present with pancreatic cancer can undergo surgery with potentially curative intent. Among these patients, we’ve viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone. For the first time, we now have another option that appears superior to gemcitabine in this setting, improving the cure rate for patients with pancreatic cancer that is resectable.
 |
|
S-1 is an oral formulation that contains three different components. One component, tegafur, is turned into 5-fluorouracil (5-FU) in the bloodstream. 5-FU is a commonly used drug in pancreatic cancer and other types of cancers worldwide. The other components of S-1 are added to improve the effectiveness of the tegafur and to reduce its side effects.
Oral capecitabine, which is available in the United States for a variety of cancers, also gets turned into 5-FU in the bloodstream. S-1 is similar, but with these other ingredients. S-1 is licensed in other countries and is in clinical development with the potential for future licensing in the United States. There’s a question of dosing and how the side effects profile might differ in different populations.
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
Dr. Philip A. Philip,
To put this into perspective, pancreatic cancer worldwide remains a highly lethal disease, yet about a third of patients who present with pancreatic cancer can undergo surgery with potentially curative intent. Among these patients, we’ve viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone. For the first time, we now have another option that appears superior to gemcitabine in this setting, improving the cure rate for patients with pancreatic cancer that is resectable.
|
|
S-1 is an oral formulation that contains three different components. One component, tegafur, is turned into 5-fluorouracil (5-FU) in the bloodstream. 5-FU is a commonly used drug in pancreatic cancer and other types of cancers worldwide. The other components of S-1 are added to improve the effectiveness of the tegafur and to reduce its side effects.
Oral capecitabine, which is available in the United States for a variety of cancers, also gets turned into 5-FU in the bloodstream. S-1 is similar, but with these other ingredients. S-1 is licensed in other countries and is in clinical development with the potential for future licensing in the United States. There’s a question of dosing and how the side effects profile might differ in different populations.
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
To put this into perspective, pancreatic cancer worldwide remains a highly lethal disease, yet about a third of patients who present with pancreatic cancer can undergo surgery with potentially curative intent. Among these patients, we’ve viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone. For the first time, we now have another option that appears superior to gemcitabine in this setting, improving the cure rate for patients with pancreatic cancer that is resectable.
|
|
S-1 is an oral formulation that contains three different components. One component, tegafur, is turned into 5-fluorouracil (5-FU) in the bloodstream. 5-FU is a commonly used drug in pancreatic cancer and other types of cancers worldwide. The other components of S-1 are added to improve the effectiveness of the tegafur and to reduce its side effects.
Oral capecitabine, which is available in the United States for a variety of cancers, also gets turned into 5-FU in the bloodstream. S-1 is similar, but with these other ingredients. S-1 is licensed in other countries and is in clinical development with the potential for future licensing in the United States. There’s a question of dosing and how the side effects profile might differ in different populations.
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.
S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).
The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.
Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.
The study is ongoing; a final analysis is planned after 240 deaths.
S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."
Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.
Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.
Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.
Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.
In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.
On Twitter @SherryBoschert
SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.
S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).
The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.
Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.
The study is ongoing; a final analysis is planned after 240 deaths.
S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."
Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.
Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.
Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.
Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.
In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.
On Twitter @SherryBoschert
Dr. Philip A. Philip,
Dr. Philip A. Philip,
AT A MEETING ON GASTROINTESTINAL CANCERS
Major Finding: 2-year survival rates for Japanese patients who underwent resection of pancreatic cancer were 70% for those receiving postoperative S-1 and 44% for patients receiving postoperative gemcitabine.
Data Source: A preplanned interim analysis of 205 patients in an ongoing randomized, phase III clinical trial of 385 patients.
Disclosures: Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies.
Add-on nab-paclitaxel extends survival in metastatic pancreatic cancer
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
 |
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
|
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
|
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Median overall survival in patients with metastatic pancreatic cancer increased from 6.7 months on gemcitabine to 8.5 months on nab-paclitaxel plus gemcitabine.
Data Source: International phase III clinical trial of first-line therapy in 861 patients.
Disclosures: Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
Statins may reduce mortality in hepatocellular cancer
The use of statins may reduce the risk of death in patients with hepatocellular cancer by 30%, a retrospective study of 639 patients suggests.
Median overall survival from 2000 until 2011 was 22 months for the 68 statin users, significantly longer than the 18-month median survival for the 571 non-statin users, Dr. Young Kwang Chae and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO). The study won a Merit Award at the meeting.
The 30% improvement in survival with statin use also was seen in subgroups of patients who received systemic or local therapy. The benefits were still seen after controlling for the effects of age, sex, race, cancer staging, liver cirrhosis, cancer treatment, alcohol use, diabetes, and hepatitis C or hepatitis B infection.
The findings warrant a large prospective study to validate the results, said Dr. Chae, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston.
Some preclinical evidence supports the idea that statins may have antitumor activity, and several observational studies have reported inverse associations between statin use and the incidence of hepatocellular cancer.
In the current study – the largest so far to look at the effects of statins on hepatocellular cancer outcomes – median survival for all 639 patients with hepatocellular cancer was 19 months. Approximately 11% of patients reported statin use.
Statin users were significantly less likely to have underlying liver cirrhosis (48%) compared with non-statin users (64%). Only patients free of cirrhosis showed a significant, 30% decrease in mortality with statin use. The survival benefit of statins was not seen in patients with cirrhosis.
Among patients without cirrhosis, the median survival was 32 months for statin users and 22 months for non-statin users. Among patients with cirrhosis, the median survival was 18 months for statin users and 19 months for non-statin users.
There were some other significant differences between statin users and nonusers. Statin users were more likely to be aged 50 years or older (97%) compared with nonusers (86%), and more likely to have diabetes (52% and 32%, respectively).
Patients not using statins were more likely to have a history of hepatitis C or B infection (50%) compared with statin users (29%). A history of hepatitis, however, did not affect the association between statin use and improved mortality, Dr. Chae reported.
Fifty-three percent of patients in each group were treated with chemotherapy for the hepatocellular cancer. Statin users were more likely to undergo surgery (24%) or to receive local treatment (28%) compared with non-statin users, 18% of whom had surgery and 15% of whom had local treatment. The remaining option – no treatment – was more likely in non-statin users than in patients on statins (15% vs. 9%, respectively). Patients could receive more than one category of treatment.
Patients had a mean age of 63 years; 73% were male, and 66% were white. Seventy-one percent of the hepatocellular cancers were diagnosed at tumor stage III or IV.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Chae reported having no financial disclosures.
On Twitter @sherryboschert
The use of statins may reduce the risk of death in patients with hepatocellular cancer by 30%, a retrospective study of 639 patients suggests.
Median overall survival from 2000 until 2011 was 22 months for the 68 statin users, significantly longer than the 18-month median survival for the 571 non-statin users, Dr. Young Kwang Chae and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO). The study won a Merit Award at the meeting.
The 30% improvement in survival with statin use also was seen in subgroups of patients who received systemic or local therapy. The benefits were still seen after controlling for the effects of age, sex, race, cancer staging, liver cirrhosis, cancer treatment, alcohol use, diabetes, and hepatitis C or hepatitis B infection.
The findings warrant a large prospective study to validate the results, said Dr. Chae, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston.
Some preclinical evidence supports the idea that statins may have antitumor activity, and several observational studies have reported inverse associations between statin use and the incidence of hepatocellular cancer.
In the current study – the largest so far to look at the effects of statins on hepatocellular cancer outcomes – median survival for all 639 patients with hepatocellular cancer was 19 months. Approximately 11% of patients reported statin use.
Statin users were significantly less likely to have underlying liver cirrhosis (48%) compared with non-statin users (64%). Only patients free of cirrhosis showed a significant, 30% decrease in mortality with statin use. The survival benefit of statins was not seen in patients with cirrhosis.
Among patients without cirrhosis, the median survival was 32 months for statin users and 22 months for non-statin users. Among patients with cirrhosis, the median survival was 18 months for statin users and 19 months for non-statin users.
There were some other significant differences between statin users and nonusers. Statin users were more likely to be aged 50 years or older (97%) compared with nonusers (86%), and more likely to have diabetes (52% and 32%, respectively).
Patients not using statins were more likely to have a history of hepatitis C or B infection (50%) compared with statin users (29%). A history of hepatitis, however, did not affect the association between statin use and improved mortality, Dr. Chae reported.
Fifty-three percent of patients in each group were treated with chemotherapy for the hepatocellular cancer. Statin users were more likely to undergo surgery (24%) or to receive local treatment (28%) compared with non-statin users, 18% of whom had surgery and 15% of whom had local treatment. The remaining option – no treatment – was more likely in non-statin users than in patients on statins (15% vs. 9%, respectively). Patients could receive more than one category of treatment.
Patients had a mean age of 63 years; 73% were male, and 66% were white. Seventy-one percent of the hepatocellular cancers were diagnosed at tumor stage III or IV.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Chae reported having no financial disclosures.
On Twitter @sherryboschert
The use of statins may reduce the risk of death in patients with hepatocellular cancer by 30%, a retrospective study of 639 patients suggests.
Median overall survival from 2000 until 2011 was 22 months for the 68 statin users, significantly longer than the 18-month median survival for the 571 non-statin users, Dr. Young Kwang Chae and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO). The study won a Merit Award at the meeting.
The 30% improvement in survival with statin use also was seen in subgroups of patients who received systemic or local therapy. The benefits were still seen after controlling for the effects of age, sex, race, cancer staging, liver cirrhosis, cancer treatment, alcohol use, diabetes, and hepatitis C or hepatitis B infection.
The findings warrant a large prospective study to validate the results, said Dr. Chae, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston.
Some preclinical evidence supports the idea that statins may have antitumor activity, and several observational studies have reported inverse associations between statin use and the incidence of hepatocellular cancer.
In the current study – the largest so far to look at the effects of statins on hepatocellular cancer outcomes – median survival for all 639 patients with hepatocellular cancer was 19 months. Approximately 11% of patients reported statin use.
Statin users were significantly less likely to have underlying liver cirrhosis (48%) compared with non-statin users (64%). Only patients free of cirrhosis showed a significant, 30% decrease in mortality with statin use. The survival benefit of statins was not seen in patients with cirrhosis.
Among patients without cirrhosis, the median survival was 32 months for statin users and 22 months for non-statin users. Among patients with cirrhosis, the median survival was 18 months for statin users and 19 months for non-statin users.
There were some other significant differences between statin users and nonusers. Statin users were more likely to be aged 50 years or older (97%) compared with nonusers (86%), and more likely to have diabetes (52% and 32%, respectively).
Patients not using statins were more likely to have a history of hepatitis C or B infection (50%) compared with statin users (29%). A history of hepatitis, however, did not affect the association between statin use and improved mortality, Dr. Chae reported.
Fifty-three percent of patients in each group were treated with chemotherapy for the hepatocellular cancer. Statin users were more likely to undergo surgery (24%) or to receive local treatment (28%) compared with non-statin users, 18% of whom had surgery and 15% of whom had local treatment. The remaining option – no treatment – was more likely in non-statin users than in patients on statins (15% vs. 9%, respectively). Patients could receive more than one category of treatment.
Patients had a mean age of 63 years; 73% were male, and 66% were white. Seventy-one percent of the hepatocellular cancers were diagnosed at tumor stage III or IV.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Chae reported having no financial disclosures.
On Twitter @sherryboschert
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major finding: Patients with hepatocellular cancer showed significantly improved median survival if they were on statins (22 months) compared with non-statin users (18 months).
Data source: Retrospective study of 639 adults with hepatocellular cancer followed over an 11-year period from 2000 to 2011.
Disclosures: Dr. Chae reported having no financial disclosures.
Bevacizumab boosts capecitabine response in elderly with metastatic colorectal cancer
SAN FRANCISCO – Adding bevacizumab to capecitabine for first-line therapy for elderly patients with metastatic colorectal cancer significantly delayed disease progression and improved treatment response rates compared with capecitabine alone in a study of 280 patients.
The study is the first prospective, phase III clinical trial of a biologic agent (bevacizumab) for metastatic colorectal cancer in patients aged 70 years or older, who comprise many patients with this disease and generally are underrepresented in clinical trials, Dr. David Cunningham said.
Median progression-free survival rates were 5.1 months with capecitabine (Xeloda, Roche) and 9.1 months with capecitabine plus bevacizumab (Avastin, Roche/Genentech), an intent-to-treat analysis showed. Patients were followed for a median of 22 months in the monotherapy arm and 25 months in the combination therapy arm.
Among secondary outcomes, overall response rates were significantly better with the combination regimen (19%) compared with monotherapy (10%), he and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
The capecitabine/bevacizumab group also showed improved median overall survival (20.7 months) compared with the control group (16.8 months). This difference did not reach statistical significance, but the study was not powered to show a difference in overall survival. The primary outcome was progression-free survival, said Dr. Cunningham, head of the gastrointestinal unit at Royal Marsden Hospital, London.
The benefits were seen across all subgroups, he added.
The Avastin in the Elderly with Xeloda (AVEX) trial randomized elderly patients from 10 countries to first-line treatment with capecitabine 1,000 mg/m2 b.i.d. on days 1-4 with or without bevacizumab 7.5 mg/kg every 3 weeks. Patients had a median age of 76 years at enrollment and an Eastern Cooperative Oncology Group performance status of 0-2. The study recruited patients who were not considered optimal candidates for combination therapy including irinotecan or oxaliplatin. Baseline characteristics were similar between treatment groups.
Grade 3 or higher adverse events occurred in 59% of patients on the combination therapy, compared with 44% on capecitabine alone, a safety analysis on 270 patients found. Rates of any serious adverse events were 31% with combination therapy and 32% with monotherapy. Adverse events led to death in 8% of the combination group and 12% on monotherapy.
"As a clinician, I was impressed with how well tolerated this combination was," Dr. Cunningham said. No signals of unusual adverse events were seen in this older population.
Among grade 3 or higher adverse events of special interest with bevacizumab or related to chemotherapy, hypertension developed in 2.2% on the combination and 1.5% on monotherapy, venous thromboembolic events were seen in 8.2% on the combination and 4.4% on monotherapy, arterial thromboembolic events occurred in 3.7% on the combination and 1.5% on monotherapy, and proteinuria was seen in 1.5% on the combination and in no patients on monotherapy. Grade 3 or higher bleeding, pulmonary hemorrhage, or heart failure occurred in less than 1% on monotherapy and no patients on combination treatment.
Patients on the combination therapy were exposed to treatment for a longer duration (5.8 months) compared with those on monotherapy (4.2 months). The capecitabine-plus-bevacizumab group underwent a median of nine cycles of therapy compared with six cycles in the capecitabine group.
The combination treatment was "effective, generally well tolerated, and produced meaningful disease control and good survival," Dr. Cunningham said. Because the multicenter study included patients from around the world, "these results should be transferable" and generalizable to elderly patients with metastatic colorectal cancer, he added.
Thirty-seven percent of patients in each treatment group received subsequent therapy for metastatic colorectal cancer.
Bevacizumab is considered part of standard care for metastatic colorectal cancer in general, and prior studies had suggested that elderly patients would benefit from adding bevacizumab to chemotherapy, he said.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
On Twitter @sherryboschert
SAN FRANCISCO – Adding bevacizumab to capecitabine for first-line therapy for elderly patients with metastatic colorectal cancer significantly delayed disease progression and improved treatment response rates compared with capecitabine alone in a study of 280 patients.
The study is the first prospective, phase III clinical trial of a biologic agent (bevacizumab) for metastatic colorectal cancer in patients aged 70 years or older, who comprise many patients with this disease and generally are underrepresented in clinical trials, Dr. David Cunningham said.
Median progression-free survival rates were 5.1 months with capecitabine (Xeloda, Roche) and 9.1 months with capecitabine plus bevacizumab (Avastin, Roche/Genentech), an intent-to-treat analysis showed. Patients were followed for a median of 22 months in the monotherapy arm and 25 months in the combination therapy arm.
Among secondary outcomes, overall response rates were significantly better with the combination regimen (19%) compared with monotherapy (10%), he and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
The capecitabine/bevacizumab group also showed improved median overall survival (20.7 months) compared with the control group (16.8 months). This difference did not reach statistical significance, but the study was not powered to show a difference in overall survival. The primary outcome was progression-free survival, said Dr. Cunningham, head of the gastrointestinal unit at Royal Marsden Hospital, London.
The benefits were seen across all subgroups, he added.
The Avastin in the Elderly with Xeloda (AVEX) trial randomized elderly patients from 10 countries to first-line treatment with capecitabine 1,000 mg/m2 b.i.d. on days 1-4 with or without bevacizumab 7.5 mg/kg every 3 weeks. Patients had a median age of 76 years at enrollment and an Eastern Cooperative Oncology Group performance status of 0-2. The study recruited patients who were not considered optimal candidates for combination therapy including irinotecan or oxaliplatin. Baseline characteristics were similar between treatment groups.
Grade 3 or higher adverse events occurred in 59% of patients on the combination therapy, compared with 44% on capecitabine alone, a safety analysis on 270 patients found. Rates of any serious adverse events were 31% with combination therapy and 32% with monotherapy. Adverse events led to death in 8% of the combination group and 12% on monotherapy.
"As a clinician, I was impressed with how well tolerated this combination was," Dr. Cunningham said. No signals of unusual adverse events were seen in this older population.
Among grade 3 or higher adverse events of special interest with bevacizumab or related to chemotherapy, hypertension developed in 2.2% on the combination and 1.5% on monotherapy, venous thromboembolic events were seen in 8.2% on the combination and 4.4% on monotherapy, arterial thromboembolic events occurred in 3.7% on the combination and 1.5% on monotherapy, and proteinuria was seen in 1.5% on the combination and in no patients on monotherapy. Grade 3 or higher bleeding, pulmonary hemorrhage, or heart failure occurred in less than 1% on monotherapy and no patients on combination treatment.
Patients on the combination therapy were exposed to treatment for a longer duration (5.8 months) compared with those on monotherapy (4.2 months). The capecitabine-plus-bevacizumab group underwent a median of nine cycles of therapy compared with six cycles in the capecitabine group.
The combination treatment was "effective, generally well tolerated, and produced meaningful disease control and good survival," Dr. Cunningham said. Because the multicenter study included patients from around the world, "these results should be transferable" and generalizable to elderly patients with metastatic colorectal cancer, he added.
Thirty-seven percent of patients in each treatment group received subsequent therapy for metastatic colorectal cancer.
Bevacizumab is considered part of standard care for metastatic colorectal cancer in general, and prior studies had suggested that elderly patients would benefit from adding bevacizumab to chemotherapy, he said.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
On Twitter @sherryboschert
SAN FRANCISCO – Adding bevacizumab to capecitabine for first-line therapy for elderly patients with metastatic colorectal cancer significantly delayed disease progression and improved treatment response rates compared with capecitabine alone in a study of 280 patients.
The study is the first prospective, phase III clinical trial of a biologic agent (bevacizumab) for metastatic colorectal cancer in patients aged 70 years or older, who comprise many patients with this disease and generally are underrepresented in clinical trials, Dr. David Cunningham said.
Median progression-free survival rates were 5.1 months with capecitabine (Xeloda, Roche) and 9.1 months with capecitabine plus bevacizumab (Avastin, Roche/Genentech), an intent-to-treat analysis showed. Patients were followed for a median of 22 months in the monotherapy arm and 25 months in the combination therapy arm.
Among secondary outcomes, overall response rates were significantly better with the combination regimen (19%) compared with monotherapy (10%), he and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
The capecitabine/bevacizumab group also showed improved median overall survival (20.7 months) compared with the control group (16.8 months). This difference did not reach statistical significance, but the study was not powered to show a difference in overall survival. The primary outcome was progression-free survival, said Dr. Cunningham, head of the gastrointestinal unit at Royal Marsden Hospital, London.
The benefits were seen across all subgroups, he added.
The Avastin in the Elderly with Xeloda (AVEX) trial randomized elderly patients from 10 countries to first-line treatment with capecitabine 1,000 mg/m2 b.i.d. on days 1-4 with or without bevacizumab 7.5 mg/kg every 3 weeks. Patients had a median age of 76 years at enrollment and an Eastern Cooperative Oncology Group performance status of 0-2. The study recruited patients who were not considered optimal candidates for combination therapy including irinotecan or oxaliplatin. Baseline characteristics were similar between treatment groups.
Grade 3 or higher adverse events occurred in 59% of patients on the combination therapy, compared with 44% on capecitabine alone, a safety analysis on 270 patients found. Rates of any serious adverse events were 31% with combination therapy and 32% with monotherapy. Adverse events led to death in 8% of the combination group and 12% on monotherapy.
"As a clinician, I was impressed with how well tolerated this combination was," Dr. Cunningham said. No signals of unusual adverse events were seen in this older population.
Among grade 3 or higher adverse events of special interest with bevacizumab or related to chemotherapy, hypertension developed in 2.2% on the combination and 1.5% on monotherapy, venous thromboembolic events were seen in 8.2% on the combination and 4.4% on monotherapy, arterial thromboembolic events occurred in 3.7% on the combination and 1.5% on monotherapy, and proteinuria was seen in 1.5% on the combination and in no patients on monotherapy. Grade 3 or higher bleeding, pulmonary hemorrhage, or heart failure occurred in less than 1% on monotherapy and no patients on combination treatment.
Patients on the combination therapy were exposed to treatment for a longer duration (5.8 months) compared with those on monotherapy (4.2 months). The capecitabine-plus-bevacizumab group underwent a median of nine cycles of therapy compared with six cycles in the capecitabine group.
The combination treatment was "effective, generally well tolerated, and produced meaningful disease control and good survival," Dr. Cunningham said. Because the multicenter study included patients from around the world, "these results should be transferable" and generalizable to elderly patients with metastatic colorectal cancer, he added.
Thirty-seven percent of patients in each treatment group received subsequent therapy for metastatic colorectal cancer.
Bevacizumab is considered part of standard care for metastatic colorectal cancer in general, and prior studies had suggested that elderly patients would benefit from adding bevacizumab to chemotherapy, he said.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
On Twitter @sherryboschert
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF ONCOLOGY
Major Finding: Progression-free survival improved from 5.1 months on capecitabine to 9.1 months on capecitabine plus bevacizumab in elderly patients with metastatic colorectal cancer, and overall response rates increased from 10% to 19%, respectively.
Data Source: International, randomized, controlled, open-label phase III clinical trial of 280 patients.
Disclosures: Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
