Jane Salodof MacNeil

SANTA FE, N.M. — Psychiatrists underprescribe erectile dysfunction drugs, and primary care physicians prescribe them like aspirin to virtually any man who asks, H. George Nurnberg, M.D., said at a psychiatric symposium sponsored by the University of Arizona.

Men who suffer sexual dysfunction as a side effect of antidepressants should be given phosphodiesterase-5 inhibitors to alleviate the dysfunction and thereby help ensure they continue taking the antidepressants, advised Dr. Nurnberg, director of clinical research programs in the psychiatry department at the University of New Mexico, Albuquerque. Very few psychiatrists are doing so, he said.

If, however, a seemingly healthy young or middle-aged man asks for an erectile dysfunction drug, Dr. Nurnberg said the primary care physician's first response should not be to prescribe pills but to do a thorough work-up for underlying disease. “Sexual dysfunction is a sentinel marker,” he said, warning that “it actually may be an early manifestation or marker of very significant disease, of systemic disorder, coming down the pike.”

Advertisements for sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) have obscured medical issues surrounding sexual dysfunction, Dr. Nurnberg said.

“There is a dangerous message in there. It is presented to us as a lifestyle issue,” he said. “This asymptomatic patient walking around … the assumption is he has this change in erectile dysfunction but everything else is fine.”

In most cases, this patient already has the beginnings of cardiovascular disease, he warned, predicting that as many as 30% are candidates for a myocardial infarction later in life.

Characterizing the new drugs as aspirin for erectile dysfunction, he said, “If you give the drug and they get better, that is good, but you have no idea what the etiology is. You have to think about the cause.”

Dr. Nurnberg summarized growing evidence that sexual dysfunction is a sentinel marker for endothelial dysfunction associated with major depression, medical disorders such as diabetes and cardiovascular disease, and medication side effects.

In the absence of underlying medical conditions, medications are the leading cause of sexual dysfunction, he continued. About 50% of patients discontinue antidepressants because of side effects; in patients with sexual side effects, the discontinuation rate is 90%.

Physicians ought to ask patients about any sexual consequences the patients experience while taking selective serotonin reuptake inhibitors, he said. Otherwise, “[patients] vote with their feet, and they stop taking the drug. That can be quite devastating in terms of treatment of a disorder. If we keep people on the drug, we can have better treatment outcomes.”

Some physicians choose antidepressants known to have fewer sexual side effects or augment them with bupropion, which Dr. Nurnberg said is not effective in preventing sexual dysfunction. Instead, he recommended treating the sexual side effect. Phosphodiesterase-5 inhibitors are not currently approved for women, but they might be helpful for the treatment of sexual dysfunction in females taking selective serotonin reuptake inhibitors, according to Dr. Nurnberg. With more than 4,000 women exposed to sildenafil so far, the studies have established safety but not efficacy.

He suggested the mixed results might reflect a lack of attention to women's hormone levels in most studies. In a recent trial, he reported finding significant differences over time in hormone levels of responders and nonresponders.

Previous studies did not control for hormone status. “They mixed menopausal and premenopausal women on contraceptive agents,” he said. “Estrogen status becomes very important in terms of female sexual dysfunction.”

Dr. Nurnberg disclosed receiving research support from and serving as a consultant or speaker for seven pharmaceutical companies, including Pfizer, GlaxoSmithKline, and Eli Lilly & Co., manufacturers of the three erectile dysfunction drugs.

He recommended the drug companies replace current advertisements with public service messages urging men who experience erectile dysfunction to ask their physicians for a physical examination.

SANTA FE, N.M. — Psychiatrists underprescribe erectile dysfunction drugs, and primary care physicians prescribe them like aspirin to virtually any man who asks, H. George Nurnberg, M.D., said at a psychiatric symposium sponsored by the University of Arizona.

Men who suffer sexual dysfunction as a side effect of antidepressants should be given phosphodiesterase-5 inhibitors to alleviate the dysfunction and thereby help ensure they continue taking the antidepressants, advised Dr. Nurnberg, director of clinical research programs in the psychiatry department at the University of New Mexico, Albuquerque. Very few psychiatrists are doing so, he said.

If, however, a seemingly healthy young or middle-aged man asks for an erectile dysfunction drug, Dr. Nurnberg said the primary care physician's first response should not be to prescribe pills but to do a thorough work-up for underlying disease. “Sexual dysfunction is a sentinel marker,” he said, warning that “it actually may be an early manifestation or marker of very significant disease, of systemic disorder, coming down the pike.”

Advertisements for sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) have obscured medical issues surrounding sexual dysfunction, Dr. Nurnberg said.

“There is a dangerous message in there. It is presented to us as a lifestyle issue,” he said. “This asymptomatic patient walking around … the assumption is he has this change in erectile dysfunction but everything else is fine.”

In most cases, this patient already has the beginnings of cardiovascular disease, he warned, predicting that as many as 30% are candidates for a myocardial infarction later in life.

Characterizing the new drugs as aspirin for erectile dysfunction, he said, “If you give the drug and they get better, that is good, but you have no idea what the etiology is. You have to think about the cause.”

Dr. Nurnberg summarized growing evidence that sexual dysfunction is a sentinel marker for endothelial dysfunction associated with major depression, medical disorders such as diabetes and cardiovascular disease, and medication side effects.

In the absence of underlying medical conditions, medications are the leading cause of sexual dysfunction, he continued. About 50% of patients discontinue antidepressants because of side effects; in patients with sexual side effects, the discontinuation rate is 90%.

Physicians ought to ask patients about any sexual consequences the patients experience while taking selective serotonin reuptake inhibitors, he said. Otherwise, “[patients] vote with their feet, and they stop taking the drug. That can be quite devastating in terms of treatment of a disorder. If we keep people on the drug, we can have better treatment outcomes.”

Some physicians choose antidepressants known to have fewer sexual side effects or augment them with bupropion, which Dr. Nurnberg said is not effective in preventing sexual dysfunction. Instead, he recommended treating the sexual side effect. Phosphodiesterase-5 inhibitors are not currently approved for women, but they might be helpful for the treatment of sexual dysfunction in females taking selective serotonin reuptake inhibitors, according to Dr. Nurnberg. With more than 4,000 women exposed to sildenafil so far, the studies have established safety but not efficacy.

He suggested the mixed results might reflect a lack of attention to women's hormone levels in most studies. In a recent trial, he reported finding significant differences over time in hormone levels of responders and nonresponders.

Previous studies did not control for hormone status. “They mixed menopausal and premenopausal women on contraceptive agents,” he said. “Estrogen status becomes very important in terms of female sexual dysfunction.”

Dr. Nurnberg disclosed receiving research support from and serving as a consultant or speaker for seven pharmaceutical companies, including Pfizer, GlaxoSmithKline, and Eli Lilly & Co., manufacturers of the three erectile dysfunction drugs.

He recommended the drug companies replace current advertisements with public service messages urging men who experience erectile dysfunction to ask their physicians for a physical examination.

SANTA FE, N.M. — Psychiatrists underprescribe erectile dysfunction drugs, and primary care physicians prescribe them like aspirin to virtually any man who asks, H. George Nurnberg, M.D., said at a psychiatric symposium sponsored by the University of Arizona.

Men who suffer sexual dysfunction as a side effect of antidepressants should be given phosphodiesterase-5 inhibitors to alleviate the dysfunction and thereby help ensure they continue taking the antidepressants, advised Dr. Nurnberg, director of clinical research programs in the psychiatry department at the University of New Mexico, Albuquerque. Very few psychiatrists are doing so, he said.

If, however, a seemingly healthy young or middle-aged man asks for an erectile dysfunction drug, Dr. Nurnberg said the primary care physician's first response should not be to prescribe pills but to do a thorough work-up for underlying disease. “Sexual dysfunction is a sentinel marker,” he said, warning that “it actually may be an early manifestation or marker of very significant disease, of systemic disorder, coming down the pike.”

Advertisements for sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) have obscured medical issues surrounding sexual dysfunction, Dr. Nurnberg said.

“There is a dangerous message in there. It is presented to us as a lifestyle issue,” he said. “This asymptomatic patient walking around … the assumption is he has this change in erectile dysfunction but everything else is fine.”

In most cases, this patient already has the beginnings of cardiovascular disease, he warned, predicting that as many as 30% are candidates for a myocardial infarction later in life.

Characterizing the new drugs as aspirin for erectile dysfunction, he said, “If you give the drug and they get better, that is good, but you have no idea what the etiology is. You have to think about the cause.”

Dr. Nurnberg summarized growing evidence that sexual dysfunction is a sentinel marker for endothelial dysfunction associated with major depression, medical disorders such as diabetes and cardiovascular disease, and medication side effects.

In the absence of underlying medical conditions, medications are the leading cause of sexual dysfunction, he continued. About 50% of patients discontinue antidepressants because of side effects; in patients with sexual side effects, the discontinuation rate is 90%.

Physicians ought to ask patients about any sexual consequences the patients experience while taking selective serotonin reuptake inhibitors, he said. Otherwise, “[patients] vote with their feet, and they stop taking the drug. That can be quite devastating in terms of treatment of a disorder. If we keep people on the drug, we can have better treatment outcomes.”

Some physicians choose antidepressants known to have fewer sexual side effects or augment them with bupropion, which Dr. Nurnberg said is not effective in preventing sexual dysfunction. Instead, he recommended treating the sexual side effect. Phosphodiesterase-5 inhibitors are not currently approved for women, but they might be helpful for the treatment of sexual dysfunction in females taking selective serotonin reuptake inhibitors, according to Dr. Nurnberg. With more than 4,000 women exposed to sildenafil so far, the studies have established safety but not efficacy.

He suggested the mixed results might reflect a lack of attention to women's hormone levels in most studies. In a recent trial, he reported finding significant differences over time in hormone levels of responders and nonresponders.

Previous studies did not control for hormone status. “They mixed menopausal and premenopausal women on contraceptive agents,” he said. “Estrogen status becomes very important in terms of female sexual dysfunction.”

Dr. Nurnberg disclosed receiving research support from and serving as a consultant or speaker for seven pharmaceutical companies, including Pfizer, GlaxoSmithKline, and Eli Lilly & Co., manufacturers of the three erectile dysfunction drugs.

He recommended the drug companies replace current advertisements with public service messages urging men who experience erectile dysfunction to ask their physicians for a physical examination.

ORLANDO — Swiss researchers have reported that a vaccine against nicotine addiction helped a subgroup of long-term, heavy smokers kick the habit.

The CYT002-NicQb vaccine did not perform significantly better than placebo in intent-to-treat data from a phase II clinical trial that enrolled 341 healthy smokers aged 18–70 years. Six-month results showed that 64 (40%) of 159 smokers given the vaccine and 25 (31%) of 80 smokers in the control group were able to abstain from cigarettes for 8–24 weeks.

An advantage emerged, however, when the researchers subdivided the vaccine cohort into thirds based on titers of antibodies against nicotine. Among smokers who had a high antibody response, 30 (57%) of 53 were able to quit smoking. But in both the low- and medium-antibody-response subgroups, just 17 (32%) of 53 smokers stayed off cigarettes.

“The difference between the placebo and high-response groups was highly significant,” principal investigator Jacques Cornuz, M.D., said at the annual meeting of the American Society of Clinical Oncology. “These data clearly suggest antibodies against nicotine are effective in helping people to quit smoking.”

The high-antibody-response group also showed an advantage among participants who cut back on smoking but did not succeed at giving up cigarettes completely, according to Dr. Cornuz of the Centre Hospitalier Universitaire Vaudois Lausanne (Switzerland). They smoked fewer cigarettes per day than the other subgroups. The response duration beyond 50 days has not been established.

In interviews after the presentation, executives from the trial's sponsor, Cytos Biotechnology of Zurich, said they plan to include a greater number of smokers who have a high response to CYT002-NicQb in a phase III trial scheduled for 2007. The company has announced its goal to bring the vaccine to market by the end of 2009.

A spin-off from the Swiss Federal Institute of Technology, Cytos is also working on vaccines against obesity, hypertension, arthritis, psoriasis, and other chronic conditions.

Cytos president/CEO Wolfgang A. Renner and Philipp Müller, M.D., executive vice president for clinical development and regulatory affairs, said the nicotine vaccine is the most advanced among their 27 vaccine candidates for various conditions, 6 of which they described as being in development.

Dr. Cornuz and his colleagues conducted the phase II study at three centers in Switzerland. In his presentation, he said the vaccine is designed to give nicotine “the look of a virus” by coupling nicotine to a viruslike particle. The resulting antibody response interferes with the rewards of nicotine addiction by reducing the amount of nicotine entering the brain and the rate at which it enters.

The researchers enrolled people who had smoked 10–40 cigarettes a day for 3 or more years and had a Fagerström Test for Nicotine Dependence score of 5 points or more. In the vaccine and placebo groups, median values at baseline for subject characteristics were 42 years of age, 25 cigarettes smoked daily, 25 years of smoking, and a Fagerström score of 7. Both groups had a median of three failed attempts.

People with significant somatic or psychiatric diseases were excluded, as was anyone who had used any kind of smoking cessation therapy during the previous 6 months. All patients in the study received smoking cessation counseling along with five monthly doses of vaccine or placebo.

Outcomes were self-reported and were verified by carbon monoxide testing at monthly visits. Participants entered the study with median carbon monoxide concentrations in exhaled air of 29 parts per million (ppm) in the vaccine group and 27 ppm in the placebo group. The threshold for abstinence was less than 10 ppm.

Dr. Cornuz reported that adverse events were common but similar overall to the severity of such events with placebo. Of the vaccine group, 68% had mild effects, 28% reported moderate effects, and 4% had severe effects.

The most frequent effects of the vaccine were flu-like symptoms after injection in nearly 70% of subjects and pyrexia and headache in about 40% each. Other common effects included nasopharyngitis (in about 30%), injection-site pain (in about 20%), and rigors and myalgia (both in about 10%). The side effects analysis was based on the 341 participants. Results excluded 44 people who used a nicotine replacement therapy and 57 for whom antibody data were incomplete.

ORLANDO — Swiss researchers have reported that a vaccine against nicotine addiction helped a subgroup of long-term, heavy smokers kick the habit.

The CYT002-NicQb vaccine did not perform significantly better than placebo in intent-to-treat data from a phase II clinical trial that enrolled 341 healthy smokers aged 18–70 years. Six-month results showed that 64 (40%) of 159 smokers given the vaccine and 25 (31%) of 80 smokers in the control group were able to abstain from cigarettes for 8–24 weeks.

An advantage emerged, however, when the researchers subdivided the vaccine cohort into thirds based on titers of antibodies against nicotine. Among smokers who had a high antibody response, 30 (57%) of 53 were able to quit smoking. But in both the low- and medium-antibody-response subgroups, just 17 (32%) of 53 smokers stayed off cigarettes.

“The difference between the placebo and high-response groups was highly significant,” principal investigator Jacques Cornuz, M.D., said at the annual meeting of the American Society of Clinical Oncology. “These data clearly suggest antibodies against nicotine are effective in helping people to quit smoking.”

The high-antibody-response group also showed an advantage among participants who cut back on smoking but did not succeed at giving up cigarettes completely, according to Dr. Cornuz of the Centre Hospitalier Universitaire Vaudois Lausanne (Switzerland). They smoked fewer cigarettes per day than the other subgroups. The response duration beyond 50 days has not been established.

In interviews after the presentation, executives from the trial's sponsor, Cytos Biotechnology of Zurich, said they plan to include a greater number of smokers who have a high response to CYT002-NicQb in a phase III trial scheduled for 2007. The company has announced its goal to bring the vaccine to market by the end of 2009.

A spin-off from the Swiss Federal Institute of Technology, Cytos is also working on vaccines against obesity, hypertension, arthritis, psoriasis, and other chronic conditions.

Cytos president/CEO Wolfgang A. Renner and Philipp Müller, M.D., executive vice president for clinical development and regulatory affairs, said the nicotine vaccine is the most advanced among their 27 vaccine candidates for various conditions, 6 of which they described as being in development.

Dr. Cornuz and his colleagues conducted the phase II study at three centers in Switzerland. In his presentation, he said the vaccine is designed to give nicotine “the look of a virus” by coupling nicotine to a viruslike particle. The resulting antibody response interferes with the rewards of nicotine addiction by reducing the amount of nicotine entering the brain and the rate at which it enters.

The researchers enrolled people who had smoked 10–40 cigarettes a day for 3 or more years and had a Fagerström Test for Nicotine Dependence score of 5 points or more. In the vaccine and placebo groups, median values at baseline for subject characteristics were 42 years of age, 25 cigarettes smoked daily, 25 years of smoking, and a Fagerström score of 7. Both groups had a median of three failed attempts.

People with significant somatic or psychiatric diseases were excluded, as was anyone who had used any kind of smoking cessation therapy during the previous 6 months. All patients in the study received smoking cessation counseling along with five monthly doses of vaccine or placebo.

Outcomes were self-reported and were verified by carbon monoxide testing at monthly visits. Participants entered the study with median carbon monoxide concentrations in exhaled air of 29 parts per million (ppm) in the vaccine group and 27 ppm in the placebo group. The threshold for abstinence was less than 10 ppm.

Dr. Cornuz reported that adverse events were common but similar overall to the severity of such events with placebo. Of the vaccine group, 68% had mild effects, 28% reported moderate effects, and 4% had severe effects.

The most frequent effects of the vaccine were flu-like symptoms after injection in nearly 70% of subjects and pyrexia and headache in about 40% each. Other common effects included nasopharyngitis (in about 30%), injection-site pain (in about 20%), and rigors and myalgia (both in about 10%). The side effects analysis was based on the 341 participants. Results excluded 44 people who used a nicotine replacement therapy and 57 for whom antibody data were incomplete.

ORLANDO — Swiss researchers have reported that a vaccine against nicotine addiction helped a subgroup of long-term, heavy smokers kick the habit.

The CYT002-NicQb vaccine did not perform significantly better than placebo in intent-to-treat data from a phase II clinical trial that enrolled 341 healthy smokers aged 18–70 years. Six-month results showed that 64 (40%) of 159 smokers given the vaccine and 25 (31%) of 80 smokers in the control group were able to abstain from cigarettes for 8–24 weeks.

An advantage emerged, however, when the researchers subdivided the vaccine cohort into thirds based on titers of antibodies against nicotine. Among smokers who had a high antibody response, 30 (57%) of 53 were able to quit smoking. But in both the low- and medium-antibody-response subgroups, just 17 (32%) of 53 smokers stayed off cigarettes.

“The difference between the placebo and high-response groups was highly significant,” principal investigator Jacques Cornuz, M.D., said at the annual meeting of the American Society of Clinical Oncology. “These data clearly suggest antibodies against nicotine are effective in helping people to quit smoking.”

The high-antibody-response group also showed an advantage among participants who cut back on smoking but did not succeed at giving up cigarettes completely, according to Dr. Cornuz of the Centre Hospitalier Universitaire Vaudois Lausanne (Switzerland). They smoked fewer cigarettes per day than the other subgroups. The response duration beyond 50 days has not been established.

In interviews after the presentation, executives from the trial's sponsor, Cytos Biotechnology of Zurich, said they plan to include a greater number of smokers who have a high response to CYT002-NicQb in a phase III trial scheduled for 2007. The company has announced its goal to bring the vaccine to market by the end of 2009.

A spin-off from the Swiss Federal Institute of Technology, Cytos is also working on vaccines against obesity, hypertension, arthritis, psoriasis, and other chronic conditions.

Cytos president/CEO Wolfgang A. Renner and Philipp Müller, M.D., executive vice president for clinical development and regulatory affairs, said the nicotine vaccine is the most advanced among their 27 vaccine candidates for various conditions, 6 of which they described as being in development.

Dr. Cornuz and his colleagues conducted the phase II study at three centers in Switzerland. In his presentation, he said the vaccine is designed to give nicotine “the look of a virus” by coupling nicotine to a viruslike particle. The resulting antibody response interferes with the rewards of nicotine addiction by reducing the amount of nicotine entering the brain and the rate at which it enters.

The researchers enrolled people who had smoked 10–40 cigarettes a day for 3 or more years and had a Fagerström Test for Nicotine Dependence score of 5 points or more. In the vaccine and placebo groups, median values at baseline for subject characteristics were 42 years of age, 25 cigarettes smoked daily, 25 years of smoking, and a Fagerström score of 7. Both groups had a median of three failed attempts.

People with significant somatic or psychiatric diseases were excluded, as was anyone who had used any kind of smoking cessation therapy during the previous 6 months. All patients in the study received smoking cessation counseling along with five monthly doses of vaccine or placebo.

Outcomes were self-reported and were verified by carbon monoxide testing at monthly visits. Participants entered the study with median carbon monoxide concentrations in exhaled air of 29 parts per million (ppm) in the vaccine group and 27 ppm in the placebo group. The threshold for abstinence was less than 10 ppm.

Dr. Cornuz reported that adverse events were common but similar overall to the severity of such events with placebo. Of the vaccine group, 68% had mild effects, 28% reported moderate effects, and 4% had severe effects.

The most frequent effects of the vaccine were flu-like symptoms after injection in nearly 70% of subjects and pyrexia and headache in about 40% each. Other common effects included nasopharyngitis (in about 30%), injection-site pain (in about 20%), and rigors and myalgia (both in about 10%). The side effects analysis was based on the 341 participants. Results excluded 44 people who used a nicotine replacement therapy and 57 for whom antibody data were incomplete.

ORLANDO — A British study has found magnetic resonance imaging to be nearly twice as sensitive as x-ray mammography for detecting breast cancers in young women at high risk for disease due to genetic mutations or other family history of breast disease.

The finding does not resolve concerns about cost, however.

In a review of the study at the annual meeting of the American Society of Clinical Oncology, Kelly K. Hunt, M.D., calculated that magnetic resonance imaging (MRI) would find six breast cancers in 100 patients screened. “The positive predictive value being only 6%, can we really afford this?” asked Dr. Hunt of the M.D. Anderson Cancer Center in Houston.

The Magnetic Resonance Imaging for Breast Screening (MARIBS) researchers reported their conclusions simultaneously at the meeting and in The Lancet (2005;365:1769–78). Theirs is the third published study to support MRI in young high-risk women with dense breast tissue that tend to obscure tumors on mammograms (N. Engl. J. Med. 2004;351:427–37 and JAMA 2004; 292:1317–25).

All told, 35 breast cancers were found in 649 women who underwent a screening round of MRI and mammography. These cancers included 19 breast cancers detected by MRI alone and 6 by mammography alone. Only eight were detected by the two screening methods, and two were missed by both.

Investigator Martin O. Leach, Ph.D., calculated that MRI detected 77% of breast tumors, and mammography detected 40%. Combining the two technologies produced a sensitivity of 94%, which Dr. Leach of the Institute of Cancer Research in London described as “very reasonable.”

While MRI detected tumors in all risk groups enrolled in the study, it was dramatically more effective than mammography in those women who were carrying the BRCA 1 mutation. Dr. Leach reported MRI sensitivity among BRCA 1 carriers to be 92% vs. 23% with mammography.

Detected cancers were generally small (43% were less than 15 mm), high grade (54% were G3), and lymph node negative (81%), according to Dr. Leach. He said the recall rate was high, but comparable with rates in older women screened by mammography under the U.K.'s breast screening program.

The Medical Research Council and the National Health Service Research and Development Board supported the trial. The trial, begun in 1997, recruited patients at 22 genetics and MRI centers in the United Kingdom.

Enrollment in the study was limited to women who were 35–49 years of age, who were BRCA 1 or BRCA 2 carriers or who came from families with up to four cases of breast cancer in members under the age of 60 or more than four cases of breast and ovarian cancer in which the ovarian cancer occurred in women at any age. Women who reported a history of breast cancer were not included, the researchers explained.

“In younger women, 25% of cancers are missed, compared with 10% in older ages. Clearly, there's a need for more sensitive surveillance,” Dr. Leach said of the target population.

He and his colleagues concluded, “Annual screening combining MRI and [mammography] would detect most tumors in this high-risk group.”

Dr. Hunt said the most recent trial shows that MRI screening is feasible in the high-risk population.

On the issue of cost, she questioned the role of clinical breast examination in the study and of ultrasound, which she noted was used for localization, but not screening.

“The challenges will be to identify the appropriate population for screening, how frequently they should be screened, and the use of clinical breast examination, mammography and ultrasound,” Dr. Hunt said.

ORLANDO — A British study has found magnetic resonance imaging to be nearly twice as sensitive as x-ray mammography for detecting breast cancers in young women at high risk for disease due to genetic mutations or other family history of breast disease.

The finding does not resolve concerns about cost, however.

In a review of the study at the annual meeting of the American Society of Clinical Oncology, Kelly K. Hunt, M.D., calculated that magnetic resonance imaging (MRI) would find six breast cancers in 100 patients screened. “The positive predictive value being only 6%, can we really afford this?” asked Dr. Hunt of the M.D. Anderson Cancer Center in Houston.

The Magnetic Resonance Imaging for Breast Screening (MARIBS) researchers reported their conclusions simultaneously at the meeting and in The Lancet (2005;365:1769–78). Theirs is the third published study to support MRI in young high-risk women with dense breast tissue that tend to obscure tumors on mammograms (N. Engl. J. Med. 2004;351:427–37 and JAMA 2004; 292:1317–25).

All told, 35 breast cancers were found in 649 women who underwent a screening round of MRI and mammography. These cancers included 19 breast cancers detected by MRI alone and 6 by mammography alone. Only eight were detected by the two screening methods, and two were missed by both.

Investigator Martin O. Leach, Ph.D., calculated that MRI detected 77% of breast tumors, and mammography detected 40%. Combining the two technologies produced a sensitivity of 94%, which Dr. Leach of the Institute of Cancer Research in London described as “very reasonable.”

While MRI detected tumors in all risk groups enrolled in the study, it was dramatically more effective than mammography in those women who were carrying the BRCA 1 mutation. Dr. Leach reported MRI sensitivity among BRCA 1 carriers to be 92% vs. 23% with mammography.

Detected cancers were generally small (43% were less than 15 mm), high grade (54% were G3), and lymph node negative (81%), according to Dr. Leach. He said the recall rate was high, but comparable with rates in older women screened by mammography under the U.K.'s breast screening program.

The Medical Research Council and the National Health Service Research and Development Board supported the trial. The trial, begun in 1997, recruited patients at 22 genetics and MRI centers in the United Kingdom.

Enrollment in the study was limited to women who were 35–49 years of age, who were BRCA 1 or BRCA 2 carriers or who came from families with up to four cases of breast cancer in members under the age of 60 or more than four cases of breast and ovarian cancer in which the ovarian cancer occurred in women at any age. Women who reported a history of breast cancer were not included, the researchers explained.

“In younger women, 25% of cancers are missed, compared with 10% in older ages. Clearly, there's a need for more sensitive surveillance,” Dr. Leach said of the target population.

He and his colleagues concluded, “Annual screening combining MRI and [mammography] would detect most tumors in this high-risk group.”

Dr. Hunt said the most recent trial shows that MRI screening is feasible in the high-risk population.

On the issue of cost, she questioned the role of clinical breast examination in the study and of ultrasound, which she noted was used for localization, but not screening.

“The challenges will be to identify the appropriate population for screening, how frequently they should be screened, and the use of clinical breast examination, mammography and ultrasound,” Dr. Hunt said.

ORLANDO — A British study has found magnetic resonance imaging to be nearly twice as sensitive as x-ray mammography for detecting breast cancers in young women at high risk for disease due to genetic mutations or other family history of breast disease.

The finding does not resolve concerns about cost, however.

In a review of the study at the annual meeting of the American Society of Clinical Oncology, Kelly K. Hunt, M.D., calculated that magnetic resonance imaging (MRI) would find six breast cancers in 100 patients screened. “The positive predictive value being only 6%, can we really afford this?” asked Dr. Hunt of the M.D. Anderson Cancer Center in Houston.

The Magnetic Resonance Imaging for Breast Screening (MARIBS) researchers reported their conclusions simultaneously at the meeting and in The Lancet (2005;365:1769–78). Theirs is the third published study to support MRI in young high-risk women with dense breast tissue that tend to obscure tumors on mammograms (N. Engl. J. Med. 2004;351:427–37 and JAMA 2004; 292:1317–25).

All told, 35 breast cancers were found in 649 women who underwent a screening round of MRI and mammography. These cancers included 19 breast cancers detected by MRI alone and 6 by mammography alone. Only eight were detected by the two screening methods, and two were missed by both.

Investigator Martin O. Leach, Ph.D., calculated that MRI detected 77% of breast tumors, and mammography detected 40%. Combining the two technologies produced a sensitivity of 94%, which Dr. Leach of the Institute of Cancer Research in London described as “very reasonable.”

While MRI detected tumors in all risk groups enrolled in the study, it was dramatically more effective than mammography in those women who were carrying the BRCA 1 mutation. Dr. Leach reported MRI sensitivity among BRCA 1 carriers to be 92% vs. 23% with mammography.

Detected cancers were generally small (43% were less than 15 mm), high grade (54% were G3), and lymph node negative (81%), according to Dr. Leach. He said the recall rate was high, but comparable with rates in older women screened by mammography under the U.K.'s breast screening program.

The Medical Research Council and the National Health Service Research and Development Board supported the trial. The trial, begun in 1997, recruited patients at 22 genetics and MRI centers in the United Kingdom.

Enrollment in the study was limited to women who were 35–49 years of age, who were BRCA 1 or BRCA 2 carriers or who came from families with up to four cases of breast cancer in members under the age of 60 or more than four cases of breast and ovarian cancer in which the ovarian cancer occurred in women at any age. Women who reported a history of breast cancer were not included, the researchers explained.

“In younger women, 25% of cancers are missed, compared with 10% in older ages. Clearly, there's a need for more sensitive surveillance,” Dr. Leach said of the target population.

He and his colleagues concluded, “Annual screening combining MRI and [mammography] would detect most tumors in this high-risk group.”

Dr. Hunt said the most recent trial shows that MRI screening is feasible in the high-risk population.

On the issue of cost, she questioned the role of clinical breast examination in the study and of ultrasound, which she noted was used for localization, but not screening.

“The challenges will be to identify the appropriate population for screening, how frequently they should be screened, and the use of clinical breast examination, mammography and ultrasound,” Dr. Hunt said.

SANTA FE, N.M. – Pharmacotherapy does not cure autism, but it can make autistic children accessible to other modes of treatment, Bennett L. Leventhal, M.D., said at a psychiatric symposium sponsored by the University of Arizona.

“There are no pharmacological treatments for the cardinal symptoms of autism. Those things are not responsive to medication,” advised Dr. Leventhal, director of child and adolescent psychiatry at the University of Chicago.

“But making kids available to other interventions may help them improve,” he said.

When children are referred for pharmacotherapy, psychiatrists should begin with a complete work-up, he said. Though additional measures may be used, he said no child should be diagnosed without evaluation by two standard instruments: an Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Schedule (ADOS).

Dr. Leventhal recommended doing a physical examination with neurologic studies even if the child has been referred by a family physician. Family physicians are not equipped to examine children with disruptive behavior in their offices, he said.

Moreover, these children may have other impairments that were missed because of challenges in communicating with them. For example, he said he has seen deaf children who were classified as autistic because no one recognized hearing loss.

Attention-deficit hyperactivity disorders used to be ruled out in autistic children, he said. While these youngsters can concentrate intensely on what interests them, specialists now recognize that many autistic children have difficulty paying attention.

Dr. Leventhal said he treats them with the same stimulants used for attention deficit in children who are not autistic. “There are no studies of stimulants in children with autism, but there is no reason to think these agents would not apply here,” he said.

No one stimulant has proved better than another, he added. The biggest problem, he said, is getting autistic children to swallow pills. He suggested that that problem can be overcome by breaking up Ritalin or Adderall capsules and sprinkling the medication on food.

Dr. Leventhal recommended serotonin reuptake inhibitors (SSRIs) for control of stereotypic behaviors, such as repetitive behaviors, self-stimulatory behaviors (“stimming”), habits, and tics. He cited studies showing improvements with fluvoxamine (Arch. Gen. Psychiatry 1996;53:1001–8) and fluoxetine (Neuropsychopharmacology 2005;30:582–9).

An added benefit is SSRIs can reduce aggression, he added, describing aggression and irritability as another serious problem for people with autism. “It is one that limits access to community,” he said.

Dr. Leventhal reported that he no longer uses traditional neuroleptics because of side effects. Atypicals are coming into use, he said, but there is not much evidence in this population, except for risperidone (Risperdal).

Johnson & Johnson, parent company of risperidone maker Janssen Pharmaceutica Inc., announced in May that the Food and Drug Administration had informed the company that risperidone was “not approvable” for autism. Dr. Leventhal expressed bafflement at the decision, as he quoted data from studies that found risperidone to be effective (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:140–7; Arch. Gen. Psychiatry 1998;55:633–41; N. Engl. J. Med. 2002;347:314–21).

“There's more than ample evidence that at least risperidone as an agent leads to better overall function and reduces irritability. The FDA did not think of much of the application. It looks like ample data to me,” said Dr. Leventhal, who listed a consulting relationship with Janssen in a disclosure of interests with several pharmaceutical companies.

The risperidone doses are “relatively modest”: 1–3 mg per day, he added, reporting better outcomes and fewer side effects with lower doses. Lithium is another option that reduces aggression regardless of diagnosis or cause, according to Dr. Leventhal, who said he has also used propranolol in extreme cases.

Whatever the agent, attention to dosing is critical, Dr. Leventhal advised.

“In children with autism, side effects are very difficult to treat and very difficult to follow because these kids are not verbal,” he said. “If there are side effects, you have to look for them.”

He discouraged use of novel anticonvulsants for mood disorders, anxiolytics for anxiety disorders, and chelation to remove heavy metals when treating autistic patients. Secretin, a drug that failed several randomized trials in autism, “may actually be harmful,” he said.

Pharmacotherapy will change with development of new medications, but treatment will remain multimodal, Dr. Leventhal predicted. The cognitive enhancers approved for Alzheimer's disease are a possibility for autism, he said. “Whether it works or not is an open question. Some of our data suggest this might have some utility.”

SANTA FE, N.M. – Pharmacotherapy does not cure autism, but it can make autistic children accessible to other modes of treatment, Bennett L. Leventhal, M.D., said at a psychiatric symposium sponsored by the University of Arizona.

“There are no pharmacological treatments for the cardinal symptoms of autism. Those things are not responsive to medication,” advised Dr. Leventhal, director of child and adolescent psychiatry at the University of Chicago.

“But making kids available to other interventions may help them improve,” he said.

When children are referred for pharmacotherapy, psychiatrists should begin with a complete work-up, he said. Though additional measures may be used, he said no child should be diagnosed without evaluation by two standard instruments: an Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Schedule (ADOS).

Dr. Leventhal recommended doing a physical examination with neurologic studies even if the child has been referred by a family physician. Family physicians are not equipped to examine children with disruptive behavior in their offices, he said.

Moreover, these children may have other impairments that were missed because of challenges in communicating with them. For example, he said he has seen deaf children who were classified as autistic because no one recognized hearing loss.

Attention-deficit hyperactivity disorders used to be ruled out in autistic children, he said. While these youngsters can concentrate intensely on what interests them, specialists now recognize that many autistic children have difficulty paying attention.

Dr. Leventhal said he treats them with the same stimulants used for attention deficit in children who are not autistic. “There are no studies of stimulants in children with autism, but there is no reason to think these agents would not apply here,” he said.

No one stimulant has proved better than another, he added. The biggest problem, he said, is getting autistic children to swallow pills. He suggested that that problem can be overcome by breaking up Ritalin or Adderall capsules and sprinkling the medication on food.

Dr. Leventhal recommended serotonin reuptake inhibitors (SSRIs) for control of stereotypic behaviors, such as repetitive behaviors, self-stimulatory behaviors (“stimming”), habits, and tics. He cited studies showing improvements with fluvoxamine (Arch. Gen. Psychiatry 1996;53:1001–8) and fluoxetine (Neuropsychopharmacology 2005;30:582–9).

An added benefit is SSRIs can reduce aggression, he added, describing aggression and irritability as another serious problem for people with autism. “It is one that limits access to community,” he said.

Dr. Leventhal reported that he no longer uses traditional neuroleptics because of side effects. Atypicals are coming into use, he said, but there is not much evidence in this population, except for risperidone (Risperdal).

Johnson & Johnson, parent company of risperidone maker Janssen Pharmaceutica Inc., announced in May that the Food and Drug Administration had informed the company that risperidone was “not approvable” for autism. Dr. Leventhal expressed bafflement at the decision, as he quoted data from studies that found risperidone to be effective (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:140–7; Arch. Gen. Psychiatry 1998;55:633–41; N. Engl. J. Med. 2002;347:314–21).

“There's more than ample evidence that at least risperidone as an agent leads to better overall function and reduces irritability. The FDA did not think of much of the application. It looks like ample data to me,” said Dr. Leventhal, who listed a consulting relationship with Janssen in a disclosure of interests with several pharmaceutical companies.

The risperidone doses are “relatively modest”: 1–3 mg per day, he added, reporting better outcomes and fewer side effects with lower doses. Lithium is another option that reduces aggression regardless of diagnosis or cause, according to Dr. Leventhal, who said he has also used propranolol in extreme cases.

Whatever the agent, attention to dosing is critical, Dr. Leventhal advised.

“In children with autism, side effects are very difficult to treat and very difficult to follow because these kids are not verbal,” he said. “If there are side effects, you have to look for them.”

He discouraged use of novel anticonvulsants for mood disorders, anxiolytics for anxiety disorders, and chelation to remove heavy metals when treating autistic patients. Secretin, a drug that failed several randomized trials in autism, “may actually be harmful,” he said.

Pharmacotherapy will change with development of new medications, but treatment will remain multimodal, Dr. Leventhal predicted. The cognitive enhancers approved for Alzheimer's disease are a possibility for autism, he said. “Whether it works or not is an open question. Some of our data suggest this might have some utility.”

SANTA FE, N.M. – Pharmacotherapy does not cure autism, but it can make autistic children accessible to other modes of treatment, Bennett L. Leventhal, M.D., said at a psychiatric symposium sponsored by the University of Arizona.

“There are no pharmacological treatments for the cardinal symptoms of autism. Those things are not responsive to medication,” advised Dr. Leventhal, director of child and adolescent psychiatry at the University of Chicago.

“But making kids available to other interventions may help them improve,” he said.

When children are referred for pharmacotherapy, psychiatrists should begin with a complete work-up, he said. Though additional measures may be used, he said no child should be diagnosed without evaluation by two standard instruments: an Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Schedule (ADOS).

Dr. Leventhal recommended doing a physical examination with neurologic studies even if the child has been referred by a family physician. Family physicians are not equipped to examine children with disruptive behavior in their offices, he said.

Moreover, these children may have other impairments that were missed because of challenges in communicating with them. For example, he said he has seen deaf children who were classified as autistic because no one recognized hearing loss.

Attention-deficit hyperactivity disorders used to be ruled out in autistic children, he said. While these youngsters can concentrate intensely on what interests them, specialists now recognize that many autistic children have difficulty paying attention.

Dr. Leventhal said he treats them with the same stimulants used for attention deficit in children who are not autistic. “There are no studies of stimulants in children with autism, but there is no reason to think these agents would not apply here,” he said.

No one stimulant has proved better than another, he added. The biggest problem, he said, is getting autistic children to swallow pills. He suggested that that problem can be overcome by breaking up Ritalin or Adderall capsules and sprinkling the medication on food.

Dr. Leventhal recommended serotonin reuptake inhibitors (SSRIs) for control of stereotypic behaviors, such as repetitive behaviors, self-stimulatory behaviors (“stimming”), habits, and tics. He cited studies showing improvements with fluvoxamine (Arch. Gen. Psychiatry 1996;53:1001–8) and fluoxetine (Neuropsychopharmacology 2005;30:582–9).

An added benefit is SSRIs can reduce aggression, he added, describing aggression and irritability as another serious problem for people with autism. “It is one that limits access to community,” he said.

Dr. Leventhal reported that he no longer uses traditional neuroleptics because of side effects. Atypicals are coming into use, he said, but there is not much evidence in this population, except for risperidone (Risperdal).

Johnson & Johnson, parent company of risperidone maker Janssen Pharmaceutica Inc., announced in May that the Food and Drug Administration had informed the company that risperidone was “not approvable” for autism. Dr. Leventhal expressed bafflement at the decision, as he quoted data from studies that found risperidone to be effective (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:140–7; Arch. Gen. Psychiatry 1998;55:633–41; N. Engl. J. Med. 2002;347:314–21).

“There's more than ample evidence that at least risperidone as an agent leads to better overall function and reduces irritability. The FDA did not think of much of the application. It looks like ample data to me,” said Dr. Leventhal, who listed a consulting relationship with Janssen in a disclosure of interests with several pharmaceutical companies.

The risperidone doses are “relatively modest”: 1–3 mg per day, he added, reporting better outcomes and fewer side effects with lower doses. Lithium is another option that reduces aggression regardless of diagnosis or cause, according to Dr. Leventhal, who said he has also used propranolol in extreme cases.

Whatever the agent, attention to dosing is critical, Dr. Leventhal advised.

“In children with autism, side effects are very difficult to treat and very difficult to follow because these kids are not verbal,” he said. “If there are side effects, you have to look for them.”

He discouraged use of novel anticonvulsants for mood disorders, anxiolytics for anxiety disorders, and chelation to remove heavy metals when treating autistic patients. Secretin, a drug that failed several randomized trials in autism, “may actually be harmful,” he said.

Pharmacotherapy will change with development of new medications, but treatment will remain multimodal, Dr. Leventhal predicted. The cognitive enhancers approved for Alzheimer's disease are a possibility for autism, he said. “Whether it works or not is an open question. Some of our data suggest this might have some utility.”

ORLANDO — Adjuvant therapy with gemcitabine (Gemzar) nearly doubled disease-free survival following surgery for pancreatic cancer in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Peter Neuhaus, M.D., reported that 179 patients given 6 months of gemcitabine chemotherapy went a median of 14.2 months before their disease recurred. In a control group of 177 patients, relapses occurred a median 7.5 months after surgery.

“For me as a surgeon, it is a milestone in the treatment of these patients because we have so long waited for a real improvement,” said Dr. Neuhaus of the Charité University Medical School in Berlin.

Earlier, he told reporters at a press briefing that this was the first prospective, randomized, and controlled trial to clearly show that adjuvant chemotherapy will help pancreatic cancer patients after surgery.

“Gemcitabine may become the standard of care for adjuvant treatment of pancreatic cancer,” he said during his presentation, predicting that favorable 3-year and 5-year survival rates will be reported with longer follow-up.

The chemotherapy drug is usually given to patients with inoperable, advanced disease. It is the only drug approved by the U.S. Food and Drug Administration for treatment of pancreatic cancer.

The investigators recruited patients with resectable disease at 88 cancer centers in Germany and Austria from July 1998 to December 2004. Participants were randomly assigned to the control or chemotherapy groups 22–24 days after surgery, creating similar cohorts with an average age of 61–62 years and slightly more men than women. In both arms, 86% of patients had stage T3 or T4 disease, and nearly three-quarters were lymph node positive. More than 80% had an R0 resection margin, and the rest were R1, because patients with more residual disease were excluded.

Patients in the adjuvant therapy arm received 1 g/m

Dr. Neuhaus reported that median disease-free survival with gemcitabine therapy was 19.3 months for node-negative patients and 13.1 months for node-positive patients. In the control group, median disease-free survival was 11.2 months for node-negative patients and 7 months for node-positive patients.

“We go one stage up in prognosis for survival of our patients,” Dr. Neuhaus said, describing the benefit to node-positive patients as one of the most striking outcomes of the study. Toxicity was low and was less than expected, he added. The most common grade 3 and 4 events with gemcitabine were low white blood cell count (8.4%), low platelet count (2.8%), nausea (4.5%), and diarrhea (2.2%).

In response to a question, Dr. Neuhaus said none of the patients received postoperative radiation, as this treatment is not used in Europe for pancreatic cancer.

Dr. Neuhaus disclosed research funding and other remuneration from Lilly Oncology.

Eileen M. O'Reilly, M.D., called the results “impressive and provocative” in a discussion of the trial. She emphasized that the findings were preliminary, however, and many questions still need to be answered, including how the investigators defined disease-free survival.

As for changing the standard of practice, Dr. O'Reilly of Memorial Sloan-Kettering Cancer Center in New York said, “There is really no globally accepted standard of care for adjuvant treatment of pancreatic cancer. Observation for patients who are fit post op is probably no longer an acceptable standard, though this is controversial.”

Erlotinib + Gemcitabine = Controversy

Adding the targeted therapy erlotinib (Tarceva) to gemcitabine produced a median survival benefit of less than 1 month for patients with inoperable pancreatic cancer in another trial reported at the meeting.

The study's outcomes were statistically significant, but controversial. Investigator Malcolm J. Moore, M.D., and discussant James L. Abbruzzese, M.D., interpreted the clinical implications in a plenary session.

Patients were enrolled from October 2001 to January 2003 at 140 centers in 17 countries for this National Cancer Institute of Canada trial. Erlotinib was added to gemcitabine because it inhibits the human epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic cancer.

Dr. Moore of Princess Margaret Hospital in Toronto said the trial was the first to show that an EGFR inhibitor can benefit patients with pancreatic cancer. He reported that 285 patients given gemcitabine and erlotinib had a 1-year survival rate of 24% and lived a median of 6.37 months. In contrast, for 284 patients given gemcitabine and placebo, the 1-year survival rate was 17%, with a median survival of 5.91 months.

The combination arm also had better progression-free survival: 3.75 months, compared with 3.55 months for patients who received the placebo. More of the patients given both agents had a tumor response as well: 57.5%, compared with 49.2% of the control group.

“Whatever subset we look at, the hazard ratio is always less than one,” said Dr. Moore, who concluded that the combination treatment improved overall survival by 19% (hazard ratio 0.81) and progression-free survival by 24% (hazard ratio 0.76).

Dr. Abbruzzese, chairman of gastrointestinal medical oncology at M.D. Anderson Cancer Center in Houston, noted that the trial had aimed for a 33% increase in median survival, not 8%. “I do not feel these results clearly alter the standard of care for patients with advanced pancreatic cancer,” he said, emphasizing that the benefit was less than a month.

Although Dr. Moore said adding erlotinib had no detrimental effects, Dr. Abbruzzese questioned whether the small survival benefits justified exposing patients to any added toxicity. He called for more studies to identify subgroups that would benefit from erlotinib, which causes a skin rash in patients who respond to therapy.

Based on the data so far, Dr. Moore said that erlotinib seemed to be most effective for subgroups of patients who were male, had poor performance status, were younger than 65 years, or had metastatic disease.

The trial's greatest benefits, he suggested, may be to focus oncologists on better understanding molecular responses to therapy, on earlier intervention in pancreatic cancer, and on determining how to identify patients who will benefit from targeted therapy.

Dr. Moore disclosed a consulting relationship with OSI Pharmaceuticals, which applied to the FDA in April for supplemental approval of erlotinib with gemcitabine in advanced pancreatic cancer. Erlotinib was approved in 2004 for use against locally advanced or metastatic non-small cell lung cancer.

ORLANDO — Adjuvant therapy with gemcitabine (Gemzar) nearly doubled disease-free survival following surgery for pancreatic cancer in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Peter Neuhaus, M.D., reported that 179 patients given 6 months of gemcitabine chemotherapy went a median of 14.2 months before their disease recurred. In a control group of 177 patients, relapses occurred a median 7.5 months after surgery.

“For me as a surgeon, it is a milestone in the treatment of these patients because we have so long waited for a real improvement,” said Dr. Neuhaus of the Charité University Medical School in Berlin.

Earlier, he told reporters at a press briefing that this was the first prospective, randomized, and controlled trial to clearly show that adjuvant chemotherapy will help pancreatic cancer patients after surgery.

“Gemcitabine may become the standard of care for adjuvant treatment of pancreatic cancer,” he said during his presentation, predicting that favorable 3-year and 5-year survival rates will be reported with longer follow-up.

The chemotherapy drug is usually given to patients with inoperable, advanced disease. It is the only drug approved by the U.S. Food and Drug Administration for treatment of pancreatic cancer.

The investigators recruited patients with resectable disease at 88 cancer centers in Germany and Austria from July 1998 to December 2004. Participants were randomly assigned to the control or chemotherapy groups 22–24 days after surgery, creating similar cohorts with an average age of 61–62 years and slightly more men than women. In both arms, 86% of patients had stage T3 or T4 disease, and nearly three-quarters were lymph node positive. More than 80% had an R0 resection margin, and the rest were R1, because patients with more residual disease were excluded.

Patients in the adjuvant therapy arm received 1 g/m

Dr. Neuhaus reported that median disease-free survival with gemcitabine therapy was 19.3 months for node-negative patients and 13.1 months for node-positive patients. In the control group, median disease-free survival was 11.2 months for node-negative patients and 7 months for node-positive patients.

“We go one stage up in prognosis for survival of our patients,” Dr. Neuhaus said, describing the benefit to node-positive patients as one of the most striking outcomes of the study. Toxicity was low and was less than expected, he added. The most common grade 3 and 4 events with gemcitabine were low white blood cell count (8.4%), low platelet count (2.8%), nausea (4.5%), and diarrhea (2.2%).

In response to a question, Dr. Neuhaus said none of the patients received postoperative radiation, as this treatment is not used in Europe for pancreatic cancer.

Dr. Neuhaus disclosed research funding and other remuneration from Lilly Oncology.

Eileen M. O'Reilly, M.D., called the results “impressive and provocative” in a discussion of the trial. She emphasized that the findings were preliminary, however, and many questions still need to be answered, including how the investigators defined disease-free survival.

As for changing the standard of practice, Dr. O'Reilly of Memorial Sloan-Kettering Cancer Center in New York said, “There is really no globally accepted standard of care for adjuvant treatment of pancreatic cancer. Observation for patients who are fit post op is probably no longer an acceptable standard, though this is controversial.”

Erlotinib + Gemcitabine = Controversy

Adding the targeted therapy erlotinib (Tarceva) to gemcitabine produced a median survival benefit of less than 1 month for patients with inoperable pancreatic cancer in another trial reported at the meeting.

The study's outcomes were statistically significant, but controversial. Investigator Malcolm J. Moore, M.D., and discussant James L. Abbruzzese, M.D., interpreted the clinical implications in a plenary session.

Patients were enrolled from October 2001 to January 2003 at 140 centers in 17 countries for this National Cancer Institute of Canada trial. Erlotinib was added to gemcitabine because it inhibits the human epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic cancer.

Dr. Moore of Princess Margaret Hospital in Toronto said the trial was the first to show that an EGFR inhibitor can benefit patients with pancreatic cancer. He reported that 285 patients given gemcitabine and erlotinib had a 1-year survival rate of 24% and lived a median of 6.37 months. In contrast, for 284 patients given gemcitabine and placebo, the 1-year survival rate was 17%, with a median survival of 5.91 months.

The combination arm also had better progression-free survival: 3.75 months, compared with 3.55 months for patients who received the placebo. More of the patients given both agents had a tumor response as well: 57.5%, compared with 49.2% of the control group.

“Whatever subset we look at, the hazard ratio is always less than one,” said Dr. Moore, who concluded that the combination treatment improved overall survival by 19% (hazard ratio 0.81) and progression-free survival by 24% (hazard ratio 0.76).

Dr. Abbruzzese, chairman of gastrointestinal medical oncology at M.D. Anderson Cancer Center in Houston, noted that the trial had aimed for a 33% increase in median survival, not 8%. “I do not feel these results clearly alter the standard of care for patients with advanced pancreatic cancer,” he said, emphasizing that the benefit was less than a month.

Although Dr. Moore said adding erlotinib had no detrimental effects, Dr. Abbruzzese questioned whether the small survival benefits justified exposing patients to any added toxicity. He called for more studies to identify subgroups that would benefit from erlotinib, which causes a skin rash in patients who respond to therapy.

Based on the data so far, Dr. Moore said that erlotinib seemed to be most effective for subgroups of patients who were male, had poor performance status, were younger than 65 years, or had metastatic disease.

The trial's greatest benefits, he suggested, may be to focus oncologists on better understanding molecular responses to therapy, on earlier intervention in pancreatic cancer, and on determining how to identify patients who will benefit from targeted therapy.

Dr. Moore disclosed a consulting relationship with OSI Pharmaceuticals, which applied to the FDA in April for supplemental approval of erlotinib with gemcitabine in advanced pancreatic cancer. Erlotinib was approved in 2004 for use against locally advanced or metastatic non-small cell lung cancer.

ORLANDO — Adjuvant therapy with gemcitabine (Gemzar) nearly doubled disease-free survival following surgery for pancreatic cancer in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

Peter Neuhaus, M.D., reported that 179 patients given 6 months of gemcitabine chemotherapy went a median of 14.2 months before their disease recurred. In a control group of 177 patients, relapses occurred a median 7.5 months after surgery.

“For me as a surgeon, it is a milestone in the treatment of these patients because we have so long waited for a real improvement,” said Dr. Neuhaus of the Charité University Medical School in Berlin.

Earlier, he told reporters at a press briefing that this was the first prospective, randomized, and controlled trial to clearly show that adjuvant chemotherapy will help pancreatic cancer patients after surgery.

“Gemcitabine may become the standard of care for adjuvant treatment of pancreatic cancer,” he said during his presentation, predicting that favorable 3-year and 5-year survival rates will be reported with longer follow-up.

The chemotherapy drug is usually given to patients with inoperable, advanced disease. It is the only drug approved by the U.S. Food and Drug Administration for treatment of pancreatic cancer.

The investigators recruited patients with resectable disease at 88 cancer centers in Germany and Austria from July 1998 to December 2004. Participants were randomly assigned to the control or chemotherapy groups 22–24 days after surgery, creating similar cohorts with an average age of 61–62 years and slightly more men than women. In both arms, 86% of patients had stage T3 or T4 disease, and nearly three-quarters were lymph node positive. More than 80% had an R0 resection margin, and the rest were R1, because patients with more residual disease were excluded.

Patients in the adjuvant therapy arm received 1 g/m

Dr. Neuhaus reported that median disease-free survival with gemcitabine therapy was 19.3 months for node-negative patients and 13.1 months for node-positive patients. In the control group, median disease-free survival was 11.2 months for node-negative patients and 7 months for node-positive patients.

“We go one stage up in prognosis for survival of our patients,” Dr. Neuhaus said, describing the benefit to node-positive patients as one of the most striking outcomes of the study. Toxicity was low and was less than expected, he added. The most common grade 3 and 4 events with gemcitabine were low white blood cell count (8.4%), low platelet count (2.8%), nausea (4.5%), and diarrhea (2.2%).

In response to a question, Dr. Neuhaus said none of the patients received postoperative radiation, as this treatment is not used in Europe for pancreatic cancer.

Dr. Neuhaus disclosed research funding and other remuneration from Lilly Oncology.

Eileen M. O'Reilly, M.D., called the results “impressive and provocative” in a discussion of the trial. She emphasized that the findings were preliminary, however, and many questions still need to be answered, including how the investigators defined disease-free survival.

As for changing the standard of practice, Dr. O'Reilly of Memorial Sloan-Kettering Cancer Center in New York said, “There is really no globally accepted standard of care for adjuvant treatment of pancreatic cancer. Observation for patients who are fit post op is probably no longer an acceptable standard, though this is controversial.”

Erlotinib + Gemcitabine = Controversy

Adding the targeted therapy erlotinib (Tarceva) to gemcitabine produced a median survival benefit of less than 1 month for patients with inoperable pancreatic cancer in another trial reported at the meeting.

The study's outcomes were statistically significant, but controversial. Investigator Malcolm J. Moore, M.D., and discussant James L. Abbruzzese, M.D., interpreted the clinical implications in a plenary session.

Patients were enrolled from October 2001 to January 2003 at 140 centers in 17 countries for this National Cancer Institute of Canada trial. Erlotinib was added to gemcitabine because it inhibits the human epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic cancer.

Dr. Moore of Princess Margaret Hospital in Toronto said the trial was the first to show that an EGFR inhibitor can benefit patients with pancreatic cancer. He reported that 285 patients given gemcitabine and erlotinib had a 1-year survival rate of 24% and lived a median of 6.37 months. In contrast, for 284 patients given gemcitabine and placebo, the 1-year survival rate was 17%, with a median survival of 5.91 months.

The combination arm also had better progression-free survival: 3.75 months, compared with 3.55 months for patients who received the placebo. More of the patients given both agents had a tumor response as well: 57.5%, compared with 49.2% of the control group.

“Whatever subset we look at, the hazard ratio is always less than one,” said Dr. Moore, who concluded that the combination treatment improved overall survival by 19% (hazard ratio 0.81) and progression-free survival by 24% (hazard ratio 0.76).

Dr. Abbruzzese, chairman of gastrointestinal medical oncology at M.D. Anderson Cancer Center in Houston, noted that the trial had aimed for a 33% increase in median survival, not 8%. “I do not feel these results clearly alter the standard of care for patients with advanced pancreatic cancer,” he said, emphasizing that the benefit was less than a month.

Although Dr. Moore said adding erlotinib had no detrimental effects, Dr. Abbruzzese questioned whether the small survival benefits justified exposing patients to any added toxicity. He called for more studies to identify subgroups that would benefit from erlotinib, which causes a skin rash in patients who respond to therapy.

Based on the data so far, Dr. Moore said that erlotinib seemed to be most effective for subgroups of patients who were male, had poor performance status, were younger than 65 years, or had metastatic disease.

The trial's greatest benefits, he suggested, may be to focus oncologists on better understanding molecular responses to therapy, on earlier intervention in pancreatic cancer, and on determining how to identify patients who will benefit from targeted therapy.

Dr. Moore disclosed a consulting relationship with OSI Pharmaceuticals, which applied to the FDA in April for supplemental approval of erlotinib with gemcitabine in advanced pancreatic cancer. Erlotinib was approved in 2004 for use against locally advanced or metastatic non-small cell lung cancer.

ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.

In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.

In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.

MPA also had a better side effect profile than venlafaxine, but the North American trial did not address safety in women at risk for breast cancer.

“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview. “Whether is has a small effect on breast cancer risk of recurrence or developing or decrease is unknown.”

Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said, adding that she would consider it only if a woman has not gained relief after 4 weeks on venlafaxine.

The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline. None used medication to treat hypertension or depression.

During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day. The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.

Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was the most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of patients on venlafaxine. About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.

Four patients stopped treatment early because of side effects, and seven disappeared from follow-up.

In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.

All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was in the mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.

One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.

A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks. Their results were even better than the single-dose cohort, but their numbers were too small to compare meaningfully.

By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were free of hot flashes compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.

For the most part, MPA also was better tolerated, with patients reporting significantly less constipation, hot flash distress, abnormal sweating, and sleepiness, as well as significantly more satisfaction with hot flash control and trends toward less trouble with sleeping and orgasm.

“Based on efficacy, MPA wins. Based on acute toxicity, MPA wins. Based on cost, MPA is cheaper,” Dr. Loprinzi said, balancing the price of a single dose of MPA against daily treatment with venlafaxine.

Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.

“There is not a definitive answer,” he said. “You find circumstantial evidence on both sides of the fence.”

His group recommended discussing risks and benefits with patients. Dr. Loprinzi said he believes that risk is minimal because MPA has a half-life of 50 days.

“It is a short-term thing,” he said. “I think it allows women to gradually go through menopause.”

Black Cohosh Flunks Phase III Trial

Black cohosh, a popular herbal remedy, failed to reduce hot flashes in a randomized, double-blind, placebo-controlled, phase III crossover trial presented in another poster at the meeting.

Barbara Pockaj, M.D., and her colleagues reported that the average decrease in hot flash scores was larger in placebo users (27%) than in those who received 20 mg of black cohosh daily (20%).

At the end of the 9-week study, 36 (37%) of the 97 patients completing the study preferred placebo, 31 patients (32%) favored black cohosh, and 30 patients (30%) had no preference. The other 19 patients evaluated in the study were listed as missing. The study included breast cancer patients and women with a perceived risk of breast cancer.

Toxicity results gave a slight edge to black cohosh, with no adverse events reported by 87% of patients on the herbal remedy and 77% on placebo.

None of the findings reached statistical significance, Dr. Pockaj of the Mayo Clinic in Scottsdale, Ariz., said in an interview.

“Based on this, I see no reason to take black cohosh,” Dr. Pockaj said. “It has no effect at all, not even a suggestion.”

Black cohosh is the leading hot flash treatment in Germany, said Dr. Loibl, whose German Breast Group study showed venlafaxine to be effective for hot flashes. “I am very happy that this trial has been done finally, because it shows it [black cohosh] has no effect,” she told this newspaper.

Nonetheless, she predicted that physicians would continue to recommend the herbal remedy. Venlafaxine is not approved for hot flashes, whereas black cohosh is available over the counter, Dr. Loibl noted.

ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.

In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.

In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.

MPA also had a better side effect profile than venlafaxine, but the North American trial did not address safety in women at risk for breast cancer.

“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview. “Whether is has a small effect on breast cancer risk of recurrence or developing or decrease is unknown.”

Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said, adding that she would consider it only if a woman has not gained relief after 4 weeks on venlafaxine.

The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline. None used medication to treat hypertension or depression.

During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day. The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.

Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was the most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of patients on venlafaxine. About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.

Four patients stopped treatment early because of side effects, and seven disappeared from follow-up.

In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.

All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was in the mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.

One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.

A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks. Their results were even better than the single-dose cohort, but their numbers were too small to compare meaningfully.

By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were free of hot flashes compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.

For the most part, MPA also was better tolerated, with patients reporting significantly less constipation, hot flash distress, abnormal sweating, and sleepiness, as well as significantly more satisfaction with hot flash control and trends toward less trouble with sleeping and orgasm.

“Based on efficacy, MPA wins. Based on acute toxicity, MPA wins. Based on cost, MPA is cheaper,” Dr. Loprinzi said, balancing the price of a single dose of MPA against daily treatment with venlafaxine.

Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.

“There is not a definitive answer,” he said. “You find circumstantial evidence on both sides of the fence.”

His group recommended discussing risks and benefits with patients. Dr. Loprinzi said he believes that risk is minimal because MPA has a half-life of 50 days.

“It is a short-term thing,” he said. “I think it allows women to gradually go through menopause.”

Black Cohosh Flunks Phase III Trial

Black cohosh, a popular herbal remedy, failed to reduce hot flashes in a randomized, double-blind, placebo-controlled, phase III crossover trial presented in another poster at the meeting.

Barbara Pockaj, M.D., and her colleagues reported that the average decrease in hot flash scores was larger in placebo users (27%) than in those who received 20 mg of black cohosh daily (20%).

At the end of the 9-week study, 36 (37%) of the 97 patients completing the study preferred placebo, 31 patients (32%) favored black cohosh, and 30 patients (30%) had no preference. The other 19 patients evaluated in the study were listed as missing. The study included breast cancer patients and women with a perceived risk of breast cancer.

Toxicity results gave a slight edge to black cohosh, with no adverse events reported by 87% of patients on the herbal remedy and 77% on placebo.

None of the findings reached statistical significance, Dr. Pockaj of the Mayo Clinic in Scottsdale, Ariz., said in an interview.

“Based on this, I see no reason to take black cohosh,” Dr. Pockaj said. “It has no effect at all, not even a suggestion.”

Black cohosh is the leading hot flash treatment in Germany, said Dr. Loibl, whose German Breast Group study showed venlafaxine to be effective for hot flashes. “I am very happy that this trial has been done finally, because it shows it [black cohosh] has no effect,” she told this newspaper.

Nonetheless, she predicted that physicians would continue to recommend the herbal remedy. Venlafaxine is not approved for hot flashes, whereas black cohosh is available over the counter, Dr. Loibl noted.

ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.

In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.

In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.

MPA also had a better side effect profile than venlafaxine, but the North American trial did not address safety in women at risk for breast cancer.

“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview. “Whether is has a small effect on breast cancer risk of recurrence or developing or decrease is unknown.”

Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said, adding that she would consider it only if a woman has not gained relief after 4 weeks on venlafaxine.

The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline. None used medication to treat hypertension or depression.

During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day. The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.

Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was the most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of patients on venlafaxine. About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.

Four patients stopped treatment early because of side effects, and seven disappeared from follow-up.

In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.

All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was in the mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.

One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.

A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks. Their results were even better than the single-dose cohort, but their numbers were too small to compare meaningfully.

By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were free of hot flashes compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.

For the most part, MPA also was better tolerated, with patients reporting significantly less constipation, hot flash distress, abnormal sweating, and sleepiness, as well as significantly more satisfaction with hot flash control and trends toward less trouble with sleeping and orgasm.

“Based on efficacy, MPA wins. Based on acute toxicity, MPA wins. Based on cost, MPA is cheaper,” Dr. Loprinzi said, balancing the price of a single dose of MPA against daily treatment with venlafaxine.

Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.

“There is not a definitive answer,” he said. “You find circumstantial evidence on both sides of the fence.”

His group recommended discussing risks and benefits with patients. Dr. Loprinzi said he believes that risk is minimal because MPA has a half-life of 50 days.

“It is a short-term thing,” he said. “I think it allows women to gradually go through menopause.”

Black Cohosh Flunks Phase III Trial

Black cohosh, a popular herbal remedy, failed to reduce hot flashes in a randomized, double-blind, placebo-controlled, phase III crossover trial presented in another poster at the meeting.

Barbara Pockaj, M.D., and her colleagues reported that the average decrease in hot flash scores was larger in placebo users (27%) than in those who received 20 mg of black cohosh daily (20%).

At the end of the 9-week study, 36 (37%) of the 97 patients completing the study preferred placebo, 31 patients (32%) favored black cohosh, and 30 patients (30%) had no preference. The other 19 patients evaluated in the study were listed as missing. The study included breast cancer patients and women with a perceived risk of breast cancer.

Toxicity results gave a slight edge to black cohosh, with no adverse events reported by 87% of patients on the herbal remedy and 77% on placebo.

None of the findings reached statistical significance, Dr. Pockaj of the Mayo Clinic in Scottsdale, Ariz., said in an interview.

“Based on this, I see no reason to take black cohosh,” Dr. Pockaj said. “It has no effect at all, not even a suggestion.”

Black cohosh is the leading hot flash treatment in Germany, said Dr. Loibl, whose German Breast Group study showed venlafaxine to be effective for hot flashes. “I am very happy that this trial has been done finally, because it shows it [black cohosh] has no effect,” she told this newspaper.

Nonetheless, she predicted that physicians would continue to recommend the herbal remedy. Venlafaxine is not approved for hot flashes, whereas black cohosh is available over the counter, Dr. Loibl noted.

ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.

In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.

In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.

“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview.

Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said.

The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline; none used medication to treat hypertension or depression.

During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day.

The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.

Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of venlafaxine patients.

About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.

Four patients ended treatment because of side effects, and seven disappeared from follow-up.

In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.

All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.

One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.

A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks.

By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were hot flash free compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.

For the most part, MPA was better tolerated, with patients reporting less constipation, hot flash distress, abnormal sweating, and sleepiness.

Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.

Black Cohosh Fails Phase III Trial

Black cohosh, a popular herbal remedy, failed to reduce hot flashes in a randomized, double-blind, placebo-controlled, phase III crossover trial presented in another poster at the meeting.

Barbara Pockaj, M.D., and her colleagues reported that the average decrease in hot flash scores was larger in placebo users (27%) than in those who received 20 mg of black cohosh daily (20%).

At the end of the 9-week study, 36 (37%) of the 97 patients completing the study preferred placebo, 31 patients (32%) favored black cohosh, and 30 patients (30%) had no preference. The other 19 patients evaluated in the study were listed as missing. The study included breast cancer patients and women with a perceived risk of breast cancer.

Toxicity results gave a slight edge to black cohosh, with no adverse events reported by 87% of patients on the herbal remedy and 77% on placebo.

None of the findings reach- ed statistical significance, Dr. Pockaj of the Mayo Clinic in Scottsdale, Ariz., said in an interview.

ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.

In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.

In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.

“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview.

Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said.

The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline; none used medication to treat hypertension or depression.

During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day.

The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.

Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of venlafaxine patients.

About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.

Four patients ended treatment because of side effects, and seven disappeared from follow-up.

In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.

All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.

One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.

A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks.

By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were hot flash free compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.

For the most part, MPA was better tolerated, with patients reporting less constipation, hot flash distress, abnormal sweating, and sleepiness.

Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.

Black Cohosh Fails Phase III Trial

Black cohosh, a popular herbal remedy, failed to reduce hot flashes in a randomized, double-blind, placebo-controlled, phase III crossover trial presented in another poster at the meeting.

Barbara Pockaj, M.D., and her colleagues reported that the average decrease in hot flash scores was larger in placebo users (27%) than in those who received 20 mg of black cohosh daily (20%).

At the end of the 9-week study, 36 (37%) of the 97 patients completing the study preferred placebo, 31 patients (32%) favored black cohosh, and 30 patients (30%) had no preference. The other 19 patients evaluated in the study were listed as missing. The study included breast cancer patients and women with a perceived risk of breast cancer.

Toxicity results gave a slight edge to black cohosh, with no adverse events reported by 87% of patients on the herbal remedy and 77% on placebo.

None of the findings reach- ed statistical significance, Dr. Pockaj of the Mayo Clinic in Scottsdale, Ariz., said in an interview.

ORLANDO, FLA. — Venlafaxine controls hot flashes more effectively than clonidine, but not as well as a single dose of medroxyprogesterone acetate, according to randomized, controlled trials presented in posters at the annual meeting of the American Society of Clinical Oncology.

In a trial organized by the German Breast Group, venlafaxine (Effexor) reduced frequency of hot flashes by 62% and severity by 67% in breast cancer patients. Clonidine reduced frequency by 22% and severity by 48%, reported Sibylle Loibl, M.D.

In a North Central Cancer Treatment Group trial, venlafaxine reduced hot flash frequency by 52% and median hot flash scores by 57% in the first 185 patients evaluated. A single 400-mg dose of medroxyprogesterone (MPA, Depo-Provera) achieved an 85% drop in frequency and reduced scores by 88%, reported Charles L. Loprinzi, M.D.

“The bottom line is, it [MPA] clearly works better. I think it is a reasonable option to give,” Dr. Loprinzi, an oncologist at the Mayo Clinic, Rochester, Minn., said in an interview.

Dr. Loibl, a gynecologist in Neu-Isenburg, Germany, told this newspaper that the superiority of MPA was not surprising. “But we want to treat, especially breast cancer patients, without hormonal therapy,” she said.

The double-blind German trial randomized 80 breast cancer patients (median age 53) from April 2002 to October 2004, and was able to evaluate 69. All had at least two hot flashes per day at baseline; none used medication to treat hypertension or depression.

During the 5-week study, 34 patients took two 0.075-mg clonidine pills per day; 35 patients took venlafaxine in 37.5-mg pills, also twice a day.

The primary end point was frequency of hot flashes at 5 weeks, but the researchers also reported that venlafaxine worked faster, reducing hot flashes significantly in the first week.

Side effects were comparable with both drugs and mostly occurred in the first week. Mouth dryness was most common in both groups. Tiredness occurred in 25% of the clonidine group and 33% of venlafaxine patients.

About 25% of the venlafaxine patients experienced nausea, but Dr. Loibl said the incidence dropped nearly to zero after the first week.

Four patients ended treatment because of side effects, and seven disappeared from follow-up.

In the North American trial, almost two-thirds (63%) of the women had a history of breast cancer. The remaining 37% were afraid to take hormonal treatments because of breast cancer risk, according to Dr. Loprinzi.

All patients enrolled had at least 14 hot flashes a week. None were on antidepressants. Median age was mid-50s for all three arms of the 6-week study. The poster report on the study included data on a total of 195 patients.

One group of 94 patients started on a 37.5-mg daily dose of venlafaxine, which increased after 1 week to 75 mg. A second group of 94 patients received a single 400-mg dose of MPA.

A third group stopped accrual with seven patients because of enrollment difficulties. These patients received 500 mg of MPA every other week for 6 weeks.

By the end of the trial, Dr. Loprinzi reported that 22 patients (24%) in the one-dose MPA arm were hot flash free compared with one patient (1%) on venlafaxine. In the MPA group, 90% reported residual hot flashes scores as 49% or less of baseline, compared with 63% of those on venlafaxine.

For the most part, MPA was better tolerated, with patients reporting less constipation, hot flash distress, abnormal sweating, and sleepiness.

Safety is the big unanswered question. The concern is whether MPA interferes with hormonal therapies such as tamoxifen and aromatase inhibitors, Dr. Loprinzi said.

Black Cohosh Fails Phase III Trial

Black cohosh, a popular herbal remedy, failed to reduce hot flashes in a randomized, double-blind, placebo-controlled, phase III crossover trial presented in another poster at the meeting.

Barbara Pockaj, M.D., and her colleagues reported that the average decrease in hot flash scores was larger in placebo users (27%) than in those who received 20 mg of black cohosh daily (20%).

At the end of the 9-week study, 36 (37%) of the 97 patients completing the study preferred placebo, 31 patients (32%) favored black cohosh, and 30 patients (30%) had no preference. The other 19 patients evaluated in the study were listed as missing. The study included breast cancer patients and women with a perceived risk of breast cancer.

Toxicity results gave a slight edge to black cohosh, with no adverse events reported by 87% of patients on the herbal remedy and 77% on placebo.

None of the findings reach- ed statistical significance, Dr. Pockaj of the Mayo Clinic in Scottsdale, Ariz., said in an interview.

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva).

Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800-258-4263), which was established to monitor fetal outcomes.

The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised.

“Barrier contraception should always be used in combination with other contraceptive methods, she added.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz.

Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures.

Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote.

Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B. Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

Mr. Briggs did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV.

If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” Mr. Briggs said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive, but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day,” the pharmacist clinical specialist said.

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva).

Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800-258-4263), which was established to monitor fetal outcomes.

The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised.

“Barrier contraception should always be used in combination with other contraceptive methods, she added.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz.

Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures.

Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote.

Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B. Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

Mr. Briggs did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV.

If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” Mr. Briggs said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive, but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day,” the pharmacist clinical specialist said.

The Food and Drug Administration has downgraded efavirenz to pregnancy category D, “Positive Evidence of Fetal Risk,” and is urging women to avoid becoming pregnant while taking the antiretroviral drug.

The new package label stems from four retrospective reports of women who gave birth to infants with neural tube defects after first-trimester exposure to efavirenz (Sustiva).

Three infants were diagnosed with meningomyelocele and one with Dandy Walker syndrome.

Physicians are being asked to report pregnant patients who have been exposed to efavirenz to the Antiretroviral Pregnancy Registry (800-258-4263), which was established to monitor fetal outcomes.

The drug had previously been labeled category C: “Risk of Fetal Harm Cannot Be Ruled Out.”

Bristol-Myers Squibb Co., Princeton, N.J., alerted health care providers to the label change in a letter dated March 2005 and made public in June. Signed by Freda C. Lewis-Hall, M.D., senior vice president for medical affairs, the letter urged pregnancy testing before women start on efavirenz.

“Though there are no adequate, well-controlled studies in pregnant women, Sustiva should be used during the first trimester of pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options,” Dr. Lewis-Hall advised.

“Barrier contraception should always be used in combination with other contraceptive methods, she added.”

Dr. Lewis-Hall described a prospective review of pregnancy outcomes for 206 women who carried 207 fetuses, while exposed to efavirenz.

Five of 188 infants born after first-trimester exposure had birth defects; none were observed in 13 live births after second- or third-trimester exposures.

Dr. Lewis-Hall did not describe the birth defects, except to say they were not neural tube defects, which, so far, have only been seen in retrospective reports.

“Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz,” she wrote.

Her letter cited a preclinical animal study that reported malformations in 3 of 20 fetuses from cynomolgus monkeys treated with efavirenz throughout pregnancy.

Gerald G. Briggs, B. Pharm., told this newspaper that data from pregnancy registries and retrospective reports should be viewed as identifying possible signals and raising hypotheses.

“Follow-up controlled studies are needed to determine if the association is causative,” said Mr. Briggs, a pharmacist clinical specialist at Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., and coauthor of the reference book “Drugs in Pregnancy and Lactation” (Philadelphia: Lippincott Williams & Wilkins, 2005).

Mr. Briggs did not rule out prescribing efavirenz for a pregnant woman who is positive for HIV.

If she cannot take an alternative nonnucleoside reverse transcriptase inhibitor and has done well on efavirenz, he recommended continuing her on the drug.

“Taken in sum, the data suggest that there may be a small risk of neural tube defects and other defects, but no neural tube defects were observed in 188 prospective cases, so the risk must be low,” Mr. Briggs said.

As in all potential pregnancies, he added, the woman should be taking folic acid before conception.

“It may not be preventive, but based on the potential signal, I would recommend the same folic acid dose used for anticonvulsants known to cause neural tube defects and for women with a history of giving birth to an infant with a neural tube defect: 4 or 5 mg per day,” the pharmacist clinical specialist said.

LOS ANGELES — Pregnancies complicated by type 1 or type 2 diabetes mellitus can have good outcomes with new strategies for glucose control, Steven G. Gabbe, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

At less than 5%, the perinatal mortality rate of children whose mothers have diabetes is comparable with the rate in children of women without diabetes, according to Dr. Gabbe, dean of Vanderbilt University School of Medicine in Nashville, Tenn. Nonetheless, preventing congenital malformations and overly large babies remains a challenge.

“We have to develop individualized programs of insulin for our patients,” he said, outlining strategies that emphasize patient education and self-management.

Glucose control goals change with pregnancy, Dr. Gabbe said. Physicians should counsel diabetic women before conception to bring their glycosylated hemoglobin (HbA_1c) levels to no more than 1% above the normal range. Targeted plasma glucose levels should be 80–110 mg/dL before meals and less than 155 mg/dL after meals.

During pregnancy, target plasma glucose levels should be 60–90 mg/dL before breakfast; 60–105 mg/dL before lunch, supper, or a bedtime snack; less than 120 mg/dL 2 hours after meals; and above 60 mg/dL between 2 a.m. and 6 a.m. The mean capillary glucose level should be maintained below 100 mg/dL.

To help patients use HbA_1c levels to approximate mean glucose levels, he suggested teaching them “the rule of eights”: An HbA_1c of 8% equals 180 mg/dL, and each 1% change equals ±30 mg/dL.

Pregnant patients need to understand that there is a “lag time” between an injection of insulin and a meal (N. Engl. J. Med. 2005;352:174–83), he continued. Physicians should also warn them against “insulin stacking” in which a correction dose of insulin is given before the prior dose of prandial insulin has reached its peak effect (JAMA 2003;289:2254–64).

Insulin stacking leads to hypoglycemia, he warned. “You have to remember and remind patients about overcorrecting with too much insulin too soon before the insulin they have taken has played out.”

Dr. Gabbe said insulin levels increase during pregnancy, but the changes are different for each woman. To help the patient make adjustments, he recommended teaching her that:

▸ One unit of short-acting insulin will lower her blood glucose level by about 30 mg/dL.

▸ Ten grams of carbohydrate will elevate her blood glucose by about 30 mg/dL.

▸ One unit of short-acting insulin will cover about 10 g of carbohydrates.

He recommended the short-acting insulins lispro and aspart for pregnant patients; these can be injected or used with an insulin pump. He said there are concerns but not much experience with the long-acting insulin glargine in pregnancy.

Insulin pumps offer many advantages, he said. Along with eliminating the need for multiple injections, they provide a continuous basal rate, which reduces the risk of mean glucose excursions and hypoglycemia. Patients generally like the pump, because it allows a more flexible lifestyle.

The pumps have disadvantages, however. He said pumps require excellent patient compliance, along with intensive glucose monitoring, and can produce hypo- or hyperglycemia if mechanical problems occur. Pump failure increases the potential for ketoacidosis, and there is the potential for infection at the insertion site.

Expense is another issue. “It costs $140 more per month to use a pump vs. multiple injections,” he said.

Whatever method is used, Dr. Gabbe said diet is critical as well. Patients should have three meals and three snacks each day.

Another concern is hypoglycemia unawareness, which he warned could be exacerbated by intensive insulin therapy during pregnancy. Determine whether the patient has hypoglycemia unawareness; review and adjust her diet, insulin, and exercise; and teach family members to treat hypoglycemia, Dr. Gabbe said.

“Does all of this really make a difference?” he asked rhetorically. “Yes, it does—in having a baby that grows normally and behaves normally in the nursery.”

LOS ANGELES — Pregnancies complicated by type 1 or type 2 diabetes mellitus can have good outcomes with new strategies for glucose control, Steven G. Gabbe, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

At less than 5%, the perinatal mortality rate of children whose mothers have diabetes is comparable with the rate in children of women without diabetes, according to Dr. Gabbe, dean of Vanderbilt University School of Medicine in Nashville, Tenn. Nonetheless, preventing congenital malformations and overly large babies remains a challenge.

“We have to develop individualized programs of insulin for our patients,” he said, outlining strategies that emphasize patient education and self-management.

Glucose control goals change with pregnancy, Dr. Gabbe said. Physicians should counsel diabetic women before conception to bring their glycosylated hemoglobin (HbA_1c) levels to no more than 1% above the normal range. Targeted plasma glucose levels should be 80–110 mg/dL before meals and less than 155 mg/dL after meals.

During pregnancy, target plasma glucose levels should be 60–90 mg/dL before breakfast; 60–105 mg/dL before lunch, supper, or a bedtime snack; less than 120 mg/dL 2 hours after meals; and above 60 mg/dL between 2 a.m. and 6 a.m. The mean capillary glucose level should be maintained below 100 mg/dL.

To help patients use HbA_1c levels to approximate mean glucose levels, he suggested teaching them “the rule of eights”: An HbA_1c of 8% equals 180 mg/dL, and each 1% change equals ±30 mg/dL.

Pregnant patients need to understand that there is a “lag time” between an injection of insulin and a meal (N. Engl. J. Med. 2005;352:174–83), he continued. Physicians should also warn them against “insulin stacking” in which a correction dose of insulin is given before the prior dose of prandial insulin has reached its peak effect (JAMA 2003;289:2254–64).

Insulin stacking leads to hypoglycemia, he warned. “You have to remember and remind patients about overcorrecting with too much insulin too soon before the insulin they have taken has played out.”

Dr. Gabbe said insulin levels increase during pregnancy, but the changes are different for each woman. To help the patient make adjustments, he recommended teaching her that:

▸ One unit of short-acting insulin will lower her blood glucose level by about 30 mg/dL.

▸ Ten grams of carbohydrate will elevate her blood glucose by about 30 mg/dL.

▸ One unit of short-acting insulin will cover about 10 g of carbohydrates.

He recommended the short-acting insulins lispro and aspart for pregnant patients; these can be injected or used with an insulin pump. He said there are concerns but not much experience with the long-acting insulin glargine in pregnancy.

Insulin pumps offer many advantages, he said. Along with eliminating the need for multiple injections, they provide a continuous basal rate, which reduces the risk of mean glucose excursions and hypoglycemia. Patients generally like the pump, because it allows a more flexible lifestyle.

The pumps have disadvantages, however. He said pumps require excellent patient compliance, along with intensive glucose monitoring, and can produce hypo- or hyperglycemia if mechanical problems occur. Pump failure increases the potential for ketoacidosis, and there is the potential for infection at the insertion site.

Expense is another issue. “It costs $140 more per month to use a pump vs. multiple injections,” he said.

Whatever method is used, Dr. Gabbe said diet is critical as well. Patients should have three meals and three snacks each day.

Another concern is hypoglycemia unawareness, which he warned could be exacerbated by intensive insulin therapy during pregnancy. Determine whether the patient has hypoglycemia unawareness; review and adjust her diet, insulin, and exercise; and teach family members to treat hypoglycemia, Dr. Gabbe said.

“Does all of this really make a difference?” he asked rhetorically. “Yes, it does—in having a baby that grows normally and behaves normally in the nursery.”

LOS ANGELES — Pregnancies complicated by type 1 or type 2 diabetes mellitus can have good outcomes with new strategies for glucose control, Steven G. Gabbe, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

At less than 5%, the perinatal mortality rate of children whose mothers have diabetes is comparable with the rate in children of women without diabetes, according to Dr. Gabbe, dean of Vanderbilt University School of Medicine in Nashville, Tenn. Nonetheless, preventing congenital malformations and overly large babies remains a challenge.

“We have to develop individualized programs of insulin for our patients,” he said, outlining strategies that emphasize patient education and self-management.

Glucose control goals change with pregnancy, Dr. Gabbe said. Physicians should counsel diabetic women before conception to bring their glycosylated hemoglobin (HbA_1c) levels to no more than 1% above the normal range. Targeted plasma glucose levels should be 80–110 mg/dL before meals and less than 155 mg/dL after meals.

During pregnancy, target plasma glucose levels should be 60–90 mg/dL before breakfast; 60–105 mg/dL before lunch, supper, or a bedtime snack; less than 120 mg/dL 2 hours after meals; and above 60 mg/dL between 2 a.m. and 6 a.m. The mean capillary glucose level should be maintained below 100 mg/dL.

To help patients use HbA_1c levels to approximate mean glucose levels, he suggested teaching them “the rule of eights”: An HbA_1c of 8% equals 180 mg/dL, and each 1% change equals ±30 mg/dL.

Pregnant patients need to understand that there is a “lag time” between an injection of insulin and a meal (N. Engl. J. Med. 2005;352:174–83), he continued. Physicians should also warn them against “insulin stacking” in which a correction dose of insulin is given before the prior dose of prandial insulin has reached its peak effect (JAMA 2003;289:2254–64).

Insulin stacking leads to hypoglycemia, he warned. “You have to remember and remind patients about overcorrecting with too much insulin too soon before the insulin they have taken has played out.”

Dr. Gabbe said insulin levels increase during pregnancy, but the changes are different for each woman. To help the patient make adjustments, he recommended teaching her that:

▸ One unit of short-acting insulin will lower her blood glucose level by about 30 mg/dL.

▸ Ten grams of carbohydrate will elevate her blood glucose by about 30 mg/dL.

▸ One unit of short-acting insulin will cover about 10 g of carbohydrates.

He recommended the short-acting insulins lispro and aspart for pregnant patients; these can be injected or used with an insulin pump. He said there are concerns but not much experience with the long-acting insulin glargine in pregnancy.

Insulin pumps offer many advantages, he said. Along with eliminating the need for multiple injections, they provide a continuous basal rate, which reduces the risk of mean glucose excursions and hypoglycemia. Patients generally like the pump, because it allows a more flexible lifestyle.

The pumps have disadvantages, however. He said pumps require excellent patient compliance, along with intensive glucose monitoring, and can produce hypo- or hyperglycemia if mechanical problems occur. Pump failure increases the potential for ketoacidosis, and there is the potential for infection at the insertion site.

Expense is another issue. “It costs $140 more per month to use a pump vs. multiple injections,” he said.

Whatever method is used, Dr. Gabbe said diet is critical as well. Patients should have three meals and three snacks each day.

Another concern is hypoglycemia unawareness, which he warned could be exacerbated by intensive insulin therapy during pregnancy. Determine whether the patient has hypoglycemia unawareness; review and adjust her diet, insulin, and exercise; and teach family members to treat hypoglycemia, Dr. Gabbe said.

“Does all of this really make a difference?” he asked rhetorically. “Yes, it does—in having a baby that grows normally and behaves normally in the nursery.”

ORLANDO, FLA. — Adding the antiangiogenic agent bevacizumab to standard chemotherapies for breast cancer produced significant survival gains in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

The results were hailed both as a step into the mainstream of cancer treatment for targeted agents and as an advance likely to change the standard of care for breast cancer.

Bevacizumab, a monoclonal antibody, blocks vascular endothelial growth factor (VEGF), preventing the growth of blood vessels that feed tumors. The Food and Drug Administration approved the drug last year for the treatment of advanced colorectal cancer when used in combination with a chemotherapy regimen consisting of irinotecan plus 5-fluorouracil (5-FU) and leucovorin.

The antiangiogenic strategy, proposed in 1971 by Judah Folkman, M.D., of Children's Hospital Boston (N. Engl. J. Med. 1971;285:1182–6), was long doubted by many in the oncology community. That began to change in 2003, with the report of a 5-month survival advantage with the addition of bevacizumab to standard therapy for advanced colorectal cancer.

Genentech Inc., the maker of Avastin, supported the study. The company also is supporting clinical trials of the drug in ovarian, renal cell, and other cancers.

In the first interim report from the first trial of an antiangiogenic agent for breast cancer, bevacizumab has so far improved overall survival 33% for patients who received the agent in addition to standard first-line therapy with paclitaxel for locally recurrent or metastatic breast cancer. The multicenter trial randomized 350 patients to the bevacizumab-paclitaxel combination and 365 to standard treatment.

Principal investigator Kathy Miller, M.D., said although the data are still early, progression-free survival and response were clearly improved.

Dr. Miller of Indiana University Cancer Center in Indianapolis reported that median progression-free survival was 11.0 months in the bevacizumab-paclitaxel arm, compared with 6.1 months for women who only were treated with paclitaxel (hazard ratio 0.50). She said 28.2% responded to the combination therapy, but only 14.2% responded to paclitaxel alone.

Although 13.3% of bevacizumab patients were treated for grades 3 and 4 hypertension, Dr. Miller said side effects were manageable. Bleeding occurred in fewer than 1% and proteinuria in 2.5% of the bevacizumab patients.

Grade 3 neuropathy also was more common with bevacizumab, occurring in 19.9%, versus 13.6% of the control arm.

Commenting on the trial, Eric P. Winer, M.D., said unanswered questions include whether continuing on bevacizumab might be beneficial, and for how long.

Dr. Winer of Dana-Farber Cancer Institute in Boston said treating a breast cancer patient with bevacizumab costs $4,000 biweekly, or $104,800 for a year. He based his estimate on 95% of the wholesale price and a patient body weight of 60 kg, adding colon cancer treatment requires half the dose used in the breast cancer trial, sponsored by the National Cancer Institute and conducted by ECOG.

ORLANDO, FLA. — Adding the antiangiogenic agent bevacizumab to standard chemotherapies for breast cancer produced significant survival gains in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

The results were hailed both as a step into the mainstream of cancer treatment for targeted agents and as an advance likely to change the standard of care for breast cancer.

Bevacizumab, a monoclonal antibody, blocks vascular endothelial growth factor (VEGF), preventing the growth of blood vessels that feed tumors. The Food and Drug Administration approved the drug last year for the treatment of advanced colorectal cancer when used in combination with a chemotherapy regimen consisting of irinotecan plus 5-fluorouracil (5-FU) and leucovorin.

The antiangiogenic strategy, proposed in 1971 by Judah Folkman, M.D., of Children's Hospital Boston (N. Engl. J. Med. 1971;285:1182–6), was long doubted by many in the oncology community. That began to change in 2003, with the report of a 5-month survival advantage with the addition of bevacizumab to standard therapy for advanced colorectal cancer.

Genentech Inc., the maker of Avastin, supported the study. The company also is supporting clinical trials of the drug in ovarian, renal cell, and other cancers.

In the first interim report from the first trial of an antiangiogenic agent for breast cancer, bevacizumab has so far improved overall survival 33% for patients who received the agent in addition to standard first-line therapy with paclitaxel for locally recurrent or metastatic breast cancer. The multicenter trial randomized 350 patients to the bevacizumab-paclitaxel combination and 365 to standard treatment.

Principal investigator Kathy Miller, M.D., said although the data are still early, progression-free survival and response were clearly improved.

Dr. Miller of Indiana University Cancer Center in Indianapolis reported that median progression-free survival was 11.0 months in the bevacizumab-paclitaxel arm, compared with 6.1 months for women who only were treated with paclitaxel (hazard ratio 0.50). She said 28.2% responded to the combination therapy, but only 14.2% responded to paclitaxel alone.

Although 13.3% of bevacizumab patients were treated for grades 3 and 4 hypertension, Dr. Miller said side effects were manageable. Bleeding occurred in fewer than 1% and proteinuria in 2.5% of the bevacizumab patients.

Grade 3 neuropathy also was more common with bevacizumab, occurring in 19.9%, versus 13.6% of the control arm.

Commenting on the trial, Eric P. Winer, M.D., said unanswered questions include whether continuing on bevacizumab might be beneficial, and for how long.

Dr. Winer of Dana-Farber Cancer Institute in Boston said treating a breast cancer patient with bevacizumab costs $4,000 biweekly, or $104,800 for a year. He based his estimate on 95% of the wholesale price and a patient body weight of 60 kg, adding colon cancer treatment requires half the dose used in the breast cancer trial, sponsored by the National Cancer Institute and conducted by ECOG.

ORLANDO, FLA. — Adding the antiangiogenic agent bevacizumab to standard chemotherapies for breast cancer produced significant survival gains in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.

The results were hailed both as a step into the mainstream of cancer treatment for targeted agents and as an advance likely to change the standard of care for breast cancer.

Bevacizumab, a monoclonal antibody, blocks vascular endothelial growth factor (VEGF), preventing the growth of blood vessels that feed tumors. The Food and Drug Administration approved the drug last year for the treatment of advanced colorectal cancer when used in combination with a chemotherapy regimen consisting of irinotecan plus 5-fluorouracil (5-FU) and leucovorin.

The antiangiogenic strategy, proposed in 1971 by Judah Folkman, M.D., of Children's Hospital Boston (N. Engl. J. Med. 1971;285:1182–6), was long doubted by many in the oncology community. That began to change in 2003, with the report of a 5-month survival advantage with the addition of bevacizumab to standard therapy for advanced colorectal cancer.

Genentech Inc., the maker of Avastin, supported the study. The company also is supporting clinical trials of the drug in ovarian, renal cell, and other cancers.

In the first interim report from the first trial of an antiangiogenic agent for breast cancer, bevacizumab has so far improved overall survival 33% for patients who received the agent in addition to standard first-line therapy with paclitaxel for locally recurrent or metastatic breast cancer. The multicenter trial randomized 350 patients to the bevacizumab-paclitaxel combination and 365 to standard treatment.

Principal investigator Kathy Miller, M.D., said although the data are still early, progression-free survival and response were clearly improved.

Dr. Miller of Indiana University Cancer Center in Indianapolis reported that median progression-free survival was 11.0 months in the bevacizumab-paclitaxel arm, compared with 6.1 months for women who only were treated with paclitaxel (hazard ratio 0.50). She said 28.2% responded to the combination therapy, but only 14.2% responded to paclitaxel alone.

Although 13.3% of bevacizumab patients were treated for grades 3 and 4 hypertension, Dr. Miller said side effects were manageable. Bleeding occurred in fewer than 1% and proteinuria in 2.5% of the bevacizumab patients.

Grade 3 neuropathy also was more common with bevacizumab, occurring in 19.9%, versus 13.6% of the control arm.

Commenting on the trial, Eric P. Winer, M.D., said unanswered questions include whether continuing on bevacizumab might be beneficial, and for how long.

Dr. Winer of Dana-Farber Cancer Institute in Boston said treating a breast cancer patient with bevacizumab costs $4,000 biweekly, or $104,800 for a year. He based his estimate on 95% of the wholesale price and a patient body weight of 60 kg, adding colon cancer treatment requires half the dose used in the breast cancer trial, sponsored by the National Cancer Institute and conducted by ECOG.