Fran Lowry

CHICAGO — The diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.

Patients on metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston said in a poster at the annual meeting of the American Society of Clinical Oncology.

The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in those without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy.

Recent data suggest metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. It activates adenosine monophosphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in preclinical studies, said Dr. Jiralerspong.

He and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early-stage breast cancer. Of those, 2,374 patients did not have diabetes; 68 had diabetes and were treated with metformin, and 87 had diabetes but were not treated with metformin. The median age was 49 years, most tumors were hormone receptor-positive; 25% were HER2-positive. Patients' baseline characteristics were similar, but diabetic patients tended to be older and more obese. Metformin use was independently predictive of pCR after adjustment for diabetes, body mass index, age, stage, grade, estrogen/progesterone receptor status, and neoadjuvant taxane use.

After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, in the nondiabetic cohort (86%), compared with 81% for diabetic patients on metformin and 78% for diabetic patients not on metformin.

Dr. Jiralerspong said further studies are warranted to evaluate the potential of metformin as an antitumor agent. He said he had no conflicts of interest to declare.

CHICAGO — The diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.

Patients on metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston said in a poster at the annual meeting of the American Society of Clinical Oncology.

The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in those without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy.

Recent data suggest metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. It activates adenosine monophosphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in preclinical studies, said Dr. Jiralerspong.

He and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early-stage breast cancer. Of those, 2,374 patients did not have diabetes; 68 had diabetes and were treated with metformin, and 87 had diabetes but were not treated with metformin. The median age was 49 years, most tumors were hormone receptor-positive; 25% were HER2-positive. Patients' baseline characteristics were similar, but diabetic patients tended to be older and more obese. Metformin use was independently predictive of pCR after adjustment for diabetes, body mass index, age, stage, grade, estrogen/progesterone receptor status, and neoadjuvant taxane use.

After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, in the nondiabetic cohort (86%), compared with 81% for diabetic patients on metformin and 78% for diabetic patients not on metformin.

Dr. Jiralerspong said further studies are warranted to evaluate the potential of metformin as an antitumor agent. He said he had no conflicts of interest to declare.

CHICAGO — The diabetes drug metformin may have an antitumor effect, according to data from a retrospective study of more than 2,500 breast cancer patients, including 155 women with diabetes.

Patients on metformin for diabetes had a threefold higher pathologic complete response (pCR) rate after neoadjuvant chemotherapy, compared with those who had diabetes but were not on metformin (24% vs. 8%), Dr. Sao Jiralerspong of the University of Texas M.D. Anderson Cancer Center in Houston said in a poster at the annual meeting of the American Society of Clinical Oncology.

The rate of pCR, defined as no residual disease in the breast or lymph nodes, also was higher in the cohort of patients taking metformin than in those without diabetes, who had a pCR rate of 16% after neoadjuvant chemotherapy.

Recent data suggest metformin may reduce the incidence of cancer and cancer-related mortality in diabetic patients. It activates adenosine monophosphate-activated protein (AMP) kinase, inhibits the mammalian target of rapamycin (mTOR) pathway, and has been shown to inhibit the growth of breast cancer cell lines in preclinical studies, said Dr. Jiralerspong.

He and his colleagues reviewed the charts in the M.D. Anderson Breast Medical oncology database of 2,529 patients who received neoadjuvant systemic therapy for early-stage breast cancer. Of those, 2,374 patients did not have diabetes; 68 had diabetes and were treated with metformin, and 87 had diabetes but were not treated with metformin. The median age was 49 years, most tumors were hormone receptor-positive; 25% were HER2-positive. Patients' baseline characteristics were similar, but diabetic patients tended to be older and more obese. Metformin use was independently predictive of pCR after adjustment for diabetes, body mass index, age, stage, grade, estrogen/progesterone receptor status, and neoadjuvant taxane use.

After a median follow-up of 39 months, the recurrence-free survival was similar in the three groups. Overall survival was significantly better, in the nondiabetic cohort (86%), compared with 81% for diabetic patients on metformin and 78% for diabetic patients not on metformin.

Dr. Jiralerspong said further studies are warranted to evaluate the potential of metformin as an antitumor agent. He said he had no conflicts of interest to declare.

SAN DIEGO — A serum 25-hydroxyvitamin D level of 30 ng/mL or higher was associated with at least a 50% lower risk of breast cancer, according to the findings of a meta-analysis of three observational studies.

Together, the findings lend support for annually measuring serum vitamin D levels to better identify women at risk for breast cancer, according to the study's lead author, Dr. Cedric F. Garland, professor of family and preventive medicine at the University of California, San Diego.

Yet experts disagree on whether there is enough evidence to recommend any intervention that would inevitably result when a patient is found to have low levels of serum 25-hydroxyvitamin D (25[OH]D). “I don't care how many observational studies there are,” they don't establish causality, said Dr. Gary G. Schwartz of the departments of cancer biology and public health sciences at Wake Forest University, Winston-Salem, N.C.

That said, “There are a lot of good reasons to be concerned about vitamin D,” said Dr. Schwartz. “Low levels of the vitamin probably are related to a number of outcomes that we care about.”

The meta-analysis of data from 2,274 women with breast cancer and 2,268 controls without breast cancer indicated a linear dose-response gradient between serum 25(OH)D levels and the risk of breast cancer, Dr. Garland indicated in his poster at the annual meeting of the American Association for Cancer Research.

Dr. Garland explained that four recent observational studies showed an inverse association between serum 25(OH)D and risk of breast cancer, but did not specify the 25(OH)D serum levels associated with specific levels of reduction in breast cancer incidence. The studies for his meta-analysis were chosen because they provided data on risk of breast cancer according to quintile of serum 25(OH)D.

In the first study, researchers recruited 179 breast cancer patients and 179 controls and found that women with low levels of serum 25(OH)D and a polymorphism in the vitamin D receptor gene were 6.25 times more likely to have breast cancer, compared with women who had higher levels and no genetic polymorphism (Eur. J. Cancer 2005;41:1164–9).

In the second study, blood samples were taken from 701 cases and 724 controls and women in the highest quintile of 25(OH)D had a relative risk of 0.73 for having breast cancer, compared with those in the lowest quintile (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991–7).

In the third study, serum 25(OH)D levels were compared between 1,394 cases and 1,365 controls. Again, the researchers found that serum 25(OH)D concentrations were significantly inversely associated with postmenopausal breast cancer risk. The strongest inverse association was seen in women with levels below 50 nmol/L (20ng/mL) (Carcinogenesis 2008;29:93–9).

When the data were combined, a sigmoid dose-response gradient was observed between serum 25(OH)D and risk of breast cancer and was consistent across all studies, Dr. Garland said. He and his colleagues concluded that more cohort studies would be worthwhile but, in the meantime, public health action to raise serum 25(OH)D to 30 ng/mL or more should be started.

He commented that the pooled data from these trials add to the evidence for a link between low serum vitamin D and breast cancer, a link that he and his colleague, Dr. Edward D. Gorham, also of the University of California, San Diego, have long proposed.

“We're confident that we can prevent half the breast cancer in women in the United States, if we could raise serum vitamin D levels to 32 ng/mL,” he said.

Dr. Rowan T. Chlebowski, professor of medicine at the University of California, Los Angeles, countered, however, that it is too soon to claim that upping the intake of vitamin D can ward off breast cancer.

In 2006, Dr. Chlebowski reported that a Women's Health Initiative trial found no reduced breast cancer risk in 18,000 women randomized to 1,000 mg of calcium carbonate and 400 IU/day of vitamin D when compared with 18,000 women given a matching placebo. The results from Dr. Garland's meta-analysis “require a much more cautious interpretation,” he added. This is a selective meta-analysis. It's not comprehensive, and there are negative studies that were not included, he said.

SAN DIEGO — A serum 25-hydroxyvitamin D level of 30 ng/mL or higher was associated with at least a 50% lower risk of breast cancer, according to the findings of a meta-analysis of three observational studies.

Together, the findings lend support for annually measuring serum vitamin D levels to better identify women at risk for breast cancer, according to the study's lead author, Dr. Cedric F. Garland, professor of family and preventive medicine at the University of California, San Diego.

Yet experts disagree on whether there is enough evidence to recommend any intervention that would inevitably result when a patient is found to have low levels of serum 25-hydroxyvitamin D (25[OH]D). “I don't care how many observational studies there are,” they don't establish causality, said Dr. Gary G. Schwartz of the departments of cancer biology and public health sciences at Wake Forest University, Winston-Salem, N.C.

That said, “There are a lot of good reasons to be concerned about vitamin D,” said Dr. Schwartz. “Low levels of the vitamin probably are related to a number of outcomes that we care about.”

The meta-analysis of data from 2,274 women with breast cancer and 2,268 controls without breast cancer indicated a linear dose-response gradient between serum 25(OH)D levels and the risk of breast cancer, Dr. Garland indicated in his poster at the annual meeting of the American Association for Cancer Research.

Dr. Garland explained that four recent observational studies showed an inverse association between serum 25(OH)D and risk of breast cancer, but did not specify the 25(OH)D serum levels associated with specific levels of reduction in breast cancer incidence. The studies for his meta-analysis were chosen because they provided data on risk of breast cancer according to quintile of serum 25(OH)D.

In the first study, researchers recruited 179 breast cancer patients and 179 controls and found that women with low levels of serum 25(OH)D and a polymorphism in the vitamin D receptor gene were 6.25 times more likely to have breast cancer, compared with women who had higher levels and no genetic polymorphism (Eur. J. Cancer 2005;41:1164–9).

In the second study, blood samples were taken from 701 cases and 724 controls and women in the highest quintile of 25(OH)D had a relative risk of 0.73 for having breast cancer, compared with those in the lowest quintile (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991–7).

In the third study, serum 25(OH)D levels were compared between 1,394 cases and 1,365 controls. Again, the researchers found that serum 25(OH)D concentrations were significantly inversely associated with postmenopausal breast cancer risk. The strongest inverse association was seen in women with levels below 50 nmol/L (20ng/mL) (Carcinogenesis 2008;29:93–9).

When the data were combined, a sigmoid dose-response gradient was observed between serum 25(OH)D and risk of breast cancer and was consistent across all studies, Dr. Garland said. He and his colleagues concluded that more cohort studies would be worthwhile but, in the meantime, public health action to raise serum 25(OH)D to 30 ng/mL or more should be started.

He commented that the pooled data from these trials add to the evidence for a link between low serum vitamin D and breast cancer, a link that he and his colleague, Dr. Edward D. Gorham, also of the University of California, San Diego, have long proposed.

“We're confident that we can prevent half the breast cancer in women in the United States, if we could raise serum vitamin D levels to 32 ng/mL,” he said.

Dr. Rowan T. Chlebowski, professor of medicine at the University of California, Los Angeles, countered, however, that it is too soon to claim that upping the intake of vitamin D can ward off breast cancer.

In 2006, Dr. Chlebowski reported that a Women's Health Initiative trial found no reduced breast cancer risk in 18,000 women randomized to 1,000 mg of calcium carbonate and 400 IU/day of vitamin D when compared with 18,000 women given a matching placebo. The results from Dr. Garland's meta-analysis “require a much more cautious interpretation,” he added. This is a selective meta-analysis. It's not comprehensive, and there are negative studies that were not included, he said.

SAN DIEGO — A serum 25-hydroxyvitamin D level of 30 ng/mL or higher was associated with at least a 50% lower risk of breast cancer, according to the findings of a meta-analysis of three observational studies.

Together, the findings lend support for annually measuring serum vitamin D levels to better identify women at risk for breast cancer, according to the study's lead author, Dr. Cedric F. Garland, professor of family and preventive medicine at the University of California, San Diego.

Yet experts disagree on whether there is enough evidence to recommend any intervention that would inevitably result when a patient is found to have low levels of serum 25-hydroxyvitamin D (25[OH]D). “I don't care how many observational studies there are,” they don't establish causality, said Dr. Gary G. Schwartz of the departments of cancer biology and public health sciences at Wake Forest University, Winston-Salem, N.C.

That said, “There are a lot of good reasons to be concerned about vitamin D,” said Dr. Schwartz. “Low levels of the vitamin probably are related to a number of outcomes that we care about.”

The meta-analysis of data from 2,274 women with breast cancer and 2,268 controls without breast cancer indicated a linear dose-response gradient between serum 25(OH)D levels and the risk of breast cancer, Dr. Garland indicated in his poster at the annual meeting of the American Association for Cancer Research.

Dr. Garland explained that four recent observational studies showed an inverse association between serum 25(OH)D and risk of breast cancer, but did not specify the 25(OH)D serum levels associated with specific levels of reduction in breast cancer incidence. The studies for his meta-analysis were chosen because they provided data on risk of breast cancer according to quintile of serum 25(OH)D.

In the first study, researchers recruited 179 breast cancer patients and 179 controls and found that women with low levels of serum 25(OH)D and a polymorphism in the vitamin D receptor gene were 6.25 times more likely to have breast cancer, compared with women who had higher levels and no genetic polymorphism (Eur. J. Cancer 2005;41:1164–9).

In the second study, blood samples were taken from 701 cases and 724 controls and women in the highest quintile of 25(OH)D had a relative risk of 0.73 for having breast cancer, compared with those in the lowest quintile (Cancer Epidemiol. Biomarkers Prev. 2005;14:1991–7).

In the third study, serum 25(OH)D levels were compared between 1,394 cases and 1,365 controls. Again, the researchers found that serum 25(OH)D concentrations were significantly inversely associated with postmenopausal breast cancer risk. The strongest inverse association was seen in women with levels below 50 nmol/L (20ng/mL) (Carcinogenesis 2008;29:93–9).

When the data were combined, a sigmoid dose-response gradient was observed between serum 25(OH)D and risk of breast cancer and was consistent across all studies, Dr. Garland said. He and his colleagues concluded that more cohort studies would be worthwhile but, in the meantime, public health action to raise serum 25(OH)D to 30 ng/mL or more should be started.

He commented that the pooled data from these trials add to the evidence for a link between low serum vitamin D and breast cancer, a link that he and his colleague, Dr. Edward D. Gorham, also of the University of California, San Diego, have long proposed.

“We're confident that we can prevent half the breast cancer in women in the United States, if we could raise serum vitamin D levels to 32 ng/mL,” he said.

Dr. Rowan T. Chlebowski, professor of medicine at the University of California, Los Angeles, countered, however, that it is too soon to claim that upping the intake of vitamin D can ward off breast cancer.

In 2006, Dr. Chlebowski reported that a Women's Health Initiative trial found no reduced breast cancer risk in 18,000 women randomized to 1,000 mg of calcium carbonate and 400 IU/day of vitamin D when compared with 18,000 women given a matching placebo. The results from Dr. Garland's meta-analysis “require a much more cautious interpretation,” he added. This is a selective meta-analysis. It's not comprehensive, and there are negative studies that were not included, he said.

SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.

In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D₃ per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.

When calcium was added to the vitamin D, Bax expression increased to a lesser extent (33%), reported Veronika Fedirko, a Ph.D. candidate at Emory University's Rollins School of Public Health, Atlanta.

“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko, the lead author, said in an interview.

Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months:

▸ 2,000 mg calcium per day (n = 23).

▸ 2,000 mg calcium plus 800 IU vitamin D per day (n = 23).

▸ 800 IU vitamin D per day (n = 23).

▸ Placebo (n = 23).

Patients underwent a colorectal biopsy at study entry and another at the end of the study. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.

After 6 months of treatment, Bax expression along the full lengths of the colorectal crypts increased by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium plus vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts, the researchers said.

There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, they said.

The investigators also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium plus vitamin D group.

For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with the placebo group. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.

Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.

“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas.”

She and her colleagues, in collaboration with Dr. John D. Potter of the Fred Hutchinson Cancer Research Center, Seattle, and others, have begun another trial with calcium and vitamin D to test their efficacy in preventing adenoma recurrence. The study aims to recruit 1,300 high-risk individuals, and the dose of vitamin D will be much higher, Ms. Fedirko said.

“We used 800 IU of vitamin D in our pilot study, and I would say now even that is a low dose. When we do the other study, we will definitely increase the dose to 2,000 IU of vitamin D.”

SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.

In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D₃ per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.

When calcium was added to the vitamin D, Bax expression increased to a lesser extent (33%), reported Veronika Fedirko, a Ph.D. candidate at Emory University's Rollins School of Public Health, Atlanta.

“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko, the lead author, said in an interview.

Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months:

▸ 2,000 mg calcium per day (n = 23).

▸ 2,000 mg calcium plus 800 IU vitamin D per day (n = 23).

▸ 800 IU vitamin D per day (n = 23).

▸ Placebo (n = 23).

Patients underwent a colorectal biopsy at study entry and another at the end of the study. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.

After 6 months of treatment, Bax expression along the full lengths of the colorectal crypts increased by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium plus vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts, the researchers said.

There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, they said.

The investigators also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium plus vitamin D group.

For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with the placebo group. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.

Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.

“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas.”

She and her colleagues, in collaboration with Dr. John D. Potter of the Fred Hutchinson Cancer Research Center, Seattle, and others, have begun another trial with calcium and vitamin D to test their efficacy in preventing adenoma recurrence. The study aims to recruit 1,300 high-risk individuals, and the dose of vitamin D will be much higher, Ms. Fedirko said.

“We used 800 IU of vitamin D in our pilot study, and I would say now even that is a low dose. When we do the other study, we will definitely increase the dose to 2,000 IU of vitamin D.”

SAN DIEGO — Calcium and vitamin D supplementation may protect against colorectal cancer by creating an environment in the colon that is less conducive to the formation of polyps and adenomas.

In a pilot study presented in a poster at the annual meeting of the American Association for Cancer Research, subjects who took 800 IU of vitamin D₃ per day for 6 months increased the expression of Bax—a protein that promotes the killing of damaged cells—in their colons by 56%, compared with subjects who took placebo.

When calcium was added to the vitamin D, Bax expression increased to a lesser extent (33%), reported Veronika Fedirko, a Ph.D. candidate at Emory University's Rollins School of Public Health, Atlanta.

“We were interested in how calcium and vitamin D prevent colorectal adenomas and colorectal cancers. There is pretty good evidence for calcium, but not as much for vitamin D,” Ms. Fedirko, the lead author, said in an interview.

Ms. Fedirko and her colleagues randomized 92 patients aged 40–75 years with a history of at least one adenomatous colonic or rectal polyp within the past 36 months to receive one of the following treatments for 6 months:

▸ 2,000 mg calcium per day (n = 23).

▸ 2,000 mg calcium plus 800 IU vitamin D per day (n = 23).

▸ 800 IU vitamin D per day (n = 23).

▸ Placebo (n = 23).

Patients underwent a colorectal biopsy at study entry and another at the end of the study. The tissue samples were examined for expressions of Bcl-2, an apoptosis inhibitor, and Bax, an apoptosis promoter.

After 6 months of treatment, Bax expression along the full lengths of the colorectal crypts increased by 56% in the vitamin D-alone group, and by 33% in both the calcium alone and calcium plus vitamin D groups, relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40% of the crypts, the researchers said.

There were no statistically significant treatment effects on Bcl-2 expression, although data indicated a potential decrease in Bcl-2 expression after supplementation with calcium alone and with calcium plus vitamin D, they said.

The investigators also looked at the ratio of Bax to Bcl-2 density as an indicator of the balance of pro-apoptotic versus anti-apoptotic stimuli in the colorectal crypts. They found that the ratio of Bax to Bcl-2 increased 62% in the calcium group, 47% in the vitamin D group, and 71% in the calcium plus vitamin D group.

For the vitamin D group, the proportional increase in the Bax to Bcl-2 ratio in the upper 20% as opposed to the lower 20% of the crypts was 352%, compared with the placebo group. “It appears that the strongest treatment effect was due to vitamin D and that this occurred in the upper sections of the colon crypts,” Ms. Fedirko said.

Cells that reach the top of the colon crypt are more likely to be diseased or to have mutations, and are therefore prime candidates to be killed off, Ms. Fedirko explained. The fact that vitamin D enhanced Bax production is therefore encouraging, she said.

“Our patients already had adenomas; they have something in their colon that is not right, so supposedly they have a low rate of apoptosis to start with. If we give them vitamin D, and if this increases the level of apoptosis, they will have fewer cells that will ever get to the top of the crypt, so they will be less likely to develop adenomas.”

She and her colleagues, in collaboration with Dr. John D. Potter of the Fred Hutchinson Cancer Research Center, Seattle, and others, have begun another trial with calcium and vitamin D to test their efficacy in preventing adenoma recurrence. The study aims to recruit 1,300 high-risk individuals, and the dose of vitamin D will be much higher, Ms. Fedirko said.

“We used 800 IU of vitamin D in our pilot study, and I would say now even that is a low dose. When we do the other study, we will definitely increase the dose to 2,000 IU of vitamin D.”

HOLLYWOOD, FLA. — Cure rates for locally advanced lung cancer are increasing, but obtaining good follow-up care remains a challenge for the growing number of lung cancer survivors, Dr. Mark G. Kris told attendees at the annual conference of the National Comprehensive Cancer Network.

Lung cancer survivors are at very high risk—from 1% to 5% per year—for developing another primary cancer. As a result, they need careful surveillance and should be asked about their smoking status, which should be documented in the medical record at each follow-up office visit, said Dr. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York.

Survivors of lung cancer are also at risk for other smoking-related illnesses, such as chronic obstructive pulmonary disease and heart disease, he continued, and should be followed accordingly. In addition, radiation to the chest accelerates cardiovascular disease. As a result, lung cancer survivors need careful cardiac monitoring, including stress testing and lipid monitoring.

Radiation also accelerates osteoporosis, for which Dr. Kris said lung cancer survivors need to be prospectively treated, regardless of their general bone density, to protect against bone loss.

HOLLYWOOD, FLA. — Cure rates for locally advanced lung cancer are increasing, but obtaining good follow-up care remains a challenge for the growing number of lung cancer survivors, Dr. Mark G. Kris told attendees at the annual conference of the National Comprehensive Cancer Network.

Lung cancer survivors are at very high risk—from 1% to 5% per year—for developing another primary cancer. As a result, they need careful surveillance and should be asked about their smoking status, which should be documented in the medical record at each follow-up office visit, said Dr. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York.

Survivors of lung cancer are also at risk for other smoking-related illnesses, such as chronic obstructive pulmonary disease and heart disease, he continued, and should be followed accordingly. In addition, radiation to the chest accelerates cardiovascular disease. As a result, lung cancer survivors need careful cardiac monitoring, including stress testing and lipid monitoring.

Radiation also accelerates osteoporosis, for which Dr. Kris said lung cancer survivors need to be prospectively treated, regardless of their general bone density, to protect against bone loss.

HOLLYWOOD, FLA. — Cure rates for locally advanced lung cancer are increasing, but obtaining good follow-up care remains a challenge for the growing number of lung cancer survivors, Dr. Mark G. Kris told attendees at the annual conference of the National Comprehensive Cancer Network.

Lung cancer survivors are at very high risk—from 1% to 5% per year—for developing another primary cancer. As a result, they need careful surveillance and should be asked about their smoking status, which should be documented in the medical record at each follow-up office visit, said Dr. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York.

Survivors of lung cancer are also at risk for other smoking-related illnesses, such as chronic obstructive pulmonary disease and heart disease, he continued, and should be followed accordingly. In addition, radiation to the chest accelerates cardiovascular disease. As a result, lung cancer survivors need careful cardiac monitoring, including stress testing and lipid monitoring.

Radiation also accelerates osteoporosis, for which Dr. Kris said lung cancer survivors need to be prospectively treated, regardless of their general bone density, to protect against bone loss.

ORLANDO – A physical conditioning program that consisted of just 10 minutes a day of walking on a treadmill at a moderate pace for 3 weeks significantly improved measures of pain perception, aerobic capacity, depression, and anxiety, in chronic pain patients, according to the findings of a small, uncontrolled study.

“A frequent comorbid condition of chronic pain is profound physical deconditioning that results from inactivity. People are in too much pain to exercise or be even moderately physically active,” Amy M. Burleson, Psy.D., of the Cleveland Clinic, said in an interview.

“This inactivity often leads to depression and other mood disorders, and we know that these can exacerbate pain, so we were very pleased to see how effective this very moderate amount of exercise was in improving not only the cardiovascular fitness of our study sample, but also their mood and their pain,” she continued.

After rehabilitation programs were completed, improvements of pain, depression, and anxiety have been well documented. However, the immediate effects of brief exercise on these factors were unknown.

The investigation's 28 patients were admitted to the Cleveland Clinic's chronic pain rehabilitation program for a variety of chronic pain conditions, including low back pain, neuropathy, fibromyalgia, and migraine. They also had a psychiatric diagnosis, which included depression, anxiety, or a combination of both. Their mean age was 43 years and 53% were female, said Dr. Burleson, who presented the results at the annual meeting of the American Academy of Pain Medicine.

“The Cleveland Clinic's chronic pain program is an interdisciplinary program incorporating psychiatry, nursing, psychology, physical therapy, and addiction therapy. This is very important because treatment of chronic pain requires the expertise of multiple specialties,” Dr. Burleson said.

The exercise component consisted of a daily 10-minute walk on a treadmill. Patients began with the treadmill speed set at 1.0 mile per hour. The pace was increased by 0.5 mile per hour every 2 minutes, so that patients reached a final speed of 3.0 miles per hour, a pace that most people could manage, Dr. Burleson said.

After the 3-week program, the brief duration of daily exercise was associated with significant improvements in exercise-induced cardiac acceleration, as measured by a change in the median heart rate from 31 beats per minute to 22 beats per minute.

Patients also reported significantly less depression, anxiety, and perceived exertion. Acute antidepressant and anxiolytic effects were seen after 10 minutes of walking, as depression dropped from 6.36 to 4.86 and anxiety dropped from 5.86 to 4.07 on a 10-point Likert scale. These improvements continued to be seen at the 3-week mark.

Patients reported that it took less effort to do their treadmill walks after the 3-week program. The median exertion score on the Likert scale went from 6 to 4.

Patients' perception of pain also diminished, with Likert scale scores falling from 7.32 at baseline to 2.75 at 3 weeks.

“This research suggests that relatively modest exercise leads to improved mood and physical capacity, which has further implications for mortality risk,” she commented. “Further, it suggests that brief exercise is a safe, cost-free, nonpharmacologic strategy for immediately reducing depression and anxiety. So if we can get our chronic pain patients moving, even for short periods, it appears we can really help them feel better, both physically and mentally.”

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO – A physical conditioning program that consisted of just 10 minutes a day of walking on a treadmill at a moderate pace for 3 weeks significantly improved measures of pain perception, aerobic capacity, depression, and anxiety, in chronic pain patients, according to the findings of a small, uncontrolled study.

“A frequent comorbid condition of chronic pain is profound physical deconditioning that results from inactivity. People are in too much pain to exercise or be even moderately physically active,” Amy M. Burleson, Psy.D., of the Cleveland Clinic, said in an interview.

“This inactivity often leads to depression and other mood disorders, and we know that these can exacerbate pain, so we were very pleased to see how effective this very moderate amount of exercise was in improving not only the cardiovascular fitness of our study sample, but also their mood and their pain,” she continued.

After rehabilitation programs were completed, improvements of pain, depression, and anxiety have been well documented. However, the immediate effects of brief exercise on these factors were unknown.

The investigation's 28 patients were admitted to the Cleveland Clinic's chronic pain rehabilitation program for a variety of chronic pain conditions, including low back pain, neuropathy, fibromyalgia, and migraine. They also had a psychiatric diagnosis, which included depression, anxiety, or a combination of both. Their mean age was 43 years and 53% were female, said Dr. Burleson, who presented the results at the annual meeting of the American Academy of Pain Medicine.

“The Cleveland Clinic's chronic pain program is an interdisciplinary program incorporating psychiatry, nursing, psychology, physical therapy, and addiction therapy. This is very important because treatment of chronic pain requires the expertise of multiple specialties,” Dr. Burleson said.

The exercise component consisted of a daily 10-minute walk on a treadmill. Patients began with the treadmill speed set at 1.0 mile per hour. The pace was increased by 0.5 mile per hour every 2 minutes, so that patients reached a final speed of 3.0 miles per hour, a pace that most people could manage, Dr. Burleson said.

After the 3-week program, the brief duration of daily exercise was associated with significant improvements in exercise-induced cardiac acceleration, as measured by a change in the median heart rate from 31 beats per minute to 22 beats per minute.

Patients also reported significantly less depression, anxiety, and perceived exertion. Acute antidepressant and anxiolytic effects were seen after 10 minutes of walking, as depression dropped from 6.36 to 4.86 and anxiety dropped from 5.86 to 4.07 on a 10-point Likert scale. These improvements continued to be seen at the 3-week mark.

Patients reported that it took less effort to do their treadmill walks after the 3-week program. The median exertion score on the Likert scale went from 6 to 4.

Patients' perception of pain also diminished, with Likert scale scores falling from 7.32 at baseline to 2.75 at 3 weeks.

“This research suggests that relatively modest exercise leads to improved mood and physical capacity, which has further implications for mortality risk,” she commented. “Further, it suggests that brief exercise is a safe, cost-free, nonpharmacologic strategy for immediately reducing depression and anxiety. So if we can get our chronic pain patients moving, even for short periods, it appears we can really help them feel better, both physically and mentally.”

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO – A physical conditioning program that consisted of just 10 minutes a day of walking on a treadmill at a moderate pace for 3 weeks significantly improved measures of pain perception, aerobic capacity, depression, and anxiety, in chronic pain patients, according to the findings of a small, uncontrolled study.

“A frequent comorbid condition of chronic pain is profound physical deconditioning that results from inactivity. People are in too much pain to exercise or be even moderately physically active,” Amy M. Burleson, Psy.D., of the Cleveland Clinic, said in an interview.

“This inactivity often leads to depression and other mood disorders, and we know that these can exacerbate pain, so we were very pleased to see how effective this very moderate amount of exercise was in improving not only the cardiovascular fitness of our study sample, but also their mood and their pain,” she continued.

After rehabilitation programs were completed, improvements of pain, depression, and anxiety have been well documented. However, the immediate effects of brief exercise on these factors were unknown.

The investigation's 28 patients were admitted to the Cleveland Clinic's chronic pain rehabilitation program for a variety of chronic pain conditions, including low back pain, neuropathy, fibromyalgia, and migraine. They also had a psychiatric diagnosis, which included depression, anxiety, or a combination of both. Their mean age was 43 years and 53% were female, said Dr. Burleson, who presented the results at the annual meeting of the American Academy of Pain Medicine.

“The Cleveland Clinic's chronic pain program is an interdisciplinary program incorporating psychiatry, nursing, psychology, physical therapy, and addiction therapy. This is very important because treatment of chronic pain requires the expertise of multiple specialties,” Dr. Burleson said.

The exercise component consisted of a daily 10-minute walk on a treadmill. Patients began with the treadmill speed set at 1.0 mile per hour. The pace was increased by 0.5 mile per hour every 2 minutes, so that patients reached a final speed of 3.0 miles per hour, a pace that most people could manage, Dr. Burleson said.

After the 3-week program, the brief duration of daily exercise was associated with significant improvements in exercise-induced cardiac acceleration, as measured by a change in the median heart rate from 31 beats per minute to 22 beats per minute.

Patients also reported significantly less depression, anxiety, and perceived exertion. Acute antidepressant and anxiolytic effects were seen after 10 minutes of walking, as depression dropped from 6.36 to 4.86 and anxiety dropped from 5.86 to 4.07 on a 10-point Likert scale. These improvements continued to be seen at the 3-week mark.

Patients reported that it took less effort to do their treadmill walks after the 3-week program. The median exertion score on the Likert scale went from 6 to 4.

Patients' perception of pain also diminished, with Likert scale scores falling from 7.32 at baseline to 2.75 at 3 weeks.

“This research suggests that relatively modest exercise leads to improved mood and physical capacity, which has further implications for mortality risk,” she commented. “Further, it suggests that brief exercise is a safe, cost-free, nonpharmacologic strategy for immediately reducing depression and anxiety. So if we can get our chronic pain patients moving, even for short periods, it appears we can really help them feel better, both physically and mentally.”

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Celecoxib reduced the incidence of advanced colorectal adenomas by 41% at 5 years in high-risk patients who took the controversial COX-2 inhibitor for 3 years in a cancer prevention trial before stopping it because of cardiovascular safety concerns.

“Even 2 years after we discontinued treatment with celecoxib, our patients still derived a considerable chemoprotective benefit,” Dr. Monica Bertagnolli of Brigham and Women's Hospital, Boston, said at the annual meeting of the American Association for Cancer Research.

Just as notably, Dr. Bertagnolli reported celecoxib (Celebrex) was shown to be safe in patients who had no underlying risk factors for cardiovascular disease when they entered the study.

Dr. Bertagnolli led the Adenoma Prevention With Celecoxib (APC) trial, which began enrolling patients in 1999 and was planned to run for a total of 5 years of drug treatment. Sponsored by Pfizer Inc., the study was designed to test the efficacy and safety of two doses of celecoxib in preventing colorectal adenomas in 2,035 individuals at high risk for colon cancer.

Patients who had adenomas removed before study entry were assigned to placebo (679 patients), 200 mg twice a day of celecoxib (685), or 400 mg twice a day (671) of celecoxib. They were followed with colonoscopies performed at 1 and 3 years. Just as the last patients completed 3 years of the study, the investigators recognized increased cardiovascular toxicity with celecoxib and discontinued the drug in all patients.

“At the time we began our study, the cardiovascular toxicity of celecoxib was not known. In fact, this study was the first to unveil cardiovascular disease risk with the drug. So we did not screen any of our study population for cardiovascular risk factors. Most of our patients—84%—whose median age was 60 at the time of study entry, had at least one risk factor,” Dr. Bertagnolli explained in an interview.

The efficacy results at the 3-year point were impressive, she said. Sixty percent of the placebo group had new adenomas, compared with 43% of patients receiving 200 mg of celecoxib twice a day, and 38% of those in the high-dose group receiving 400 mg of celecoxib twice a day The reduction in the rate of new advanced adenomas was even more striking at this point, with a 64% reduction at the lower dose and a 55% reduction at the higher dose of celecoxib, she noted.

Although the patients discontinued celecoxib, Dr. Bertagnolli and her colleagues decided to continue the trial as an observational study. Approximately one-third of the original randomized cohort had a colonoscopy at 5 years as planned, she said. “We kept the study going, and I'm glad we did, because now we have interesting new data,” she said.

At 5 years, with no drug on board for 1.5-2 years, the reduction in advanced lesions was 41% in the cohort who received the lower dose of celecoxib and 26% in patients who received the higher dose. There was no rebound effect—that is, lesions did not suddenly appear when the drug was stopped, Dr Bertagnolli said.

“Interestingly, the lower dose of celecoxib was the most effective at the 5-year end point,” Dr. Bertagnolli commented.

The investigators also analyzed safety, looking at any event that occurred after patients took the first dose of celecoxib up until 30 days after they took the last dose.

Cardiovascular events (myocardial infarction, stroke, peripheral vascular disease, and vascular therapeutic procedure) rose with the dose of celecoxib, occurring in 3.8% of the patients on placebo, in 6.0% of patients on the low dose of celecoxib, and in 7.5% of patients on the high dose of celecoxib.

The data showed that patients with preexisting risk factors, defined as smoking, hypertension, diabetes, hyperlipidemia, atherosclerotic heart disease, and age over 65 years, had the greatest risk:

PIFor patients with no cardiovascular risk factors before using celecoxib, the rate of cardiovascular adverse events was 0.9% in the placebo group, 3.9% in the 200-mg b.i.d. group, and 1.9% in the 400-mg b.i.d. group.

PIIf a patient had one risk factor, the rate was 2.2% in the placebo group, 3.7% in the 200-mg b.i.d. group, and 4.9% in the 400-mg b.i.d. group.

PIAmong patients who had two or more cardiovascular risk factors at the time they entered the study, those on placebo had a cardiovascular adverse event rate of 5.9%; those on 200 mg b.i.d., 8.2%; and those on 400 mg b.i.d., 11.2%.

This risk needs to be balanced with the benefit patients derived from celecoxib, Dr. Bertagnolli said. “These patients were at very high risk for colorectal adenomas. Twenty-two percent of patients on placebo got advanced adenomas during the 5 years, and over 70% of patients had adenomas that recurred if they were on placebo. So this is a very high-risk group.”

She concluded that these new data “allow us to carefully select patients who can benefit from celecoxib. It should definitely be used with caution, but patients with a high risk for colon cancer and a low risk for cardiovascular disease are going to receive a significant benefit.”

“Studies such as Dr. Bertagnolli's are reinvigorating this avenue of research, with major implications for public health,” said Dr. Scott M. Lippman, professor of clinical cancer prevention at the University of Texas M.D. Anderson Cancer Center, Houston.

SAN DIEGO — Celecoxib reduced the incidence of advanced colorectal adenomas by 41% at 5 years in high-risk patients who took the controversial COX-2 inhibitor for 3 years in a cancer prevention trial before stopping it because of cardiovascular safety concerns.

“Even 2 years after we discontinued treatment with celecoxib, our patients still derived a considerable chemoprotective benefit,” Dr. Monica Bertagnolli of Brigham and Women's Hospital, Boston, said at the annual meeting of the American Association for Cancer Research.

Just as notably, Dr. Bertagnolli reported celecoxib (Celebrex) was shown to be safe in patients who had no underlying risk factors for cardiovascular disease when they entered the study.

Dr. Bertagnolli led the Adenoma Prevention With Celecoxib (APC) trial, which began enrolling patients in 1999 and was planned to run for a total of 5 years of drug treatment. Sponsored by Pfizer Inc., the study was designed to test the efficacy and safety of two doses of celecoxib in preventing colorectal adenomas in 2,035 individuals at high risk for colon cancer.

Patients who had adenomas removed before study entry were assigned to placebo (679 patients), 200 mg twice a day of celecoxib (685), or 400 mg twice a day (671) of celecoxib. They were followed with colonoscopies performed at 1 and 3 years. Just as the last patients completed 3 years of the study, the investigators recognized increased cardiovascular toxicity with celecoxib and discontinued the drug in all patients.

“At the time we began our study, the cardiovascular toxicity of celecoxib was not known. In fact, this study was the first to unveil cardiovascular disease risk with the drug. So we did not screen any of our study population for cardiovascular risk factors. Most of our patients—84%—whose median age was 60 at the time of study entry, had at least one risk factor,” Dr. Bertagnolli explained in an interview.

The efficacy results at the 3-year point were impressive, she said. Sixty percent of the placebo group had new adenomas, compared with 43% of patients receiving 200 mg of celecoxib twice a day, and 38% of those in the high-dose group receiving 400 mg of celecoxib twice a day The reduction in the rate of new advanced adenomas was even more striking at this point, with a 64% reduction at the lower dose and a 55% reduction at the higher dose of celecoxib, she noted.

Although the patients discontinued celecoxib, Dr. Bertagnolli and her colleagues decided to continue the trial as an observational study. Approximately one-third of the original randomized cohort had a colonoscopy at 5 years as planned, she said. “We kept the study going, and I'm glad we did, because now we have interesting new data,” she said.

At 5 years, with no drug on board for 1.5-2 years, the reduction in advanced lesions was 41% in the cohort who received the lower dose of celecoxib and 26% in patients who received the higher dose. There was no rebound effect—that is, lesions did not suddenly appear when the drug was stopped, Dr Bertagnolli said.

“Interestingly, the lower dose of celecoxib was the most effective at the 5-year end point,” Dr. Bertagnolli commented.

The investigators also analyzed safety, looking at any event that occurred after patients took the first dose of celecoxib up until 30 days after they took the last dose.

Cardiovascular events (myocardial infarction, stroke, peripheral vascular disease, and vascular therapeutic procedure) rose with the dose of celecoxib, occurring in 3.8% of the patients on placebo, in 6.0% of patients on the low dose of celecoxib, and in 7.5% of patients on the high dose of celecoxib.

The data showed that patients with preexisting risk factors, defined as smoking, hypertension, diabetes, hyperlipidemia, atherosclerotic heart disease, and age over 65 years, had the greatest risk:

PIFor patients with no cardiovascular risk factors before using celecoxib, the rate of cardiovascular adverse events was 0.9% in the placebo group, 3.9% in the 200-mg b.i.d. group, and 1.9% in the 400-mg b.i.d. group.

PIIf a patient had one risk factor, the rate was 2.2% in the placebo group, 3.7% in the 200-mg b.i.d. group, and 4.9% in the 400-mg b.i.d. group.

PIAmong patients who had two or more cardiovascular risk factors at the time they entered the study, those on placebo had a cardiovascular adverse event rate of 5.9%; those on 200 mg b.i.d., 8.2%; and those on 400 mg b.i.d., 11.2%.

This risk needs to be balanced with the benefit patients derived from celecoxib, Dr. Bertagnolli said. “These patients were at very high risk for colorectal adenomas. Twenty-two percent of patients on placebo got advanced adenomas during the 5 years, and over 70% of patients had adenomas that recurred if they were on placebo. So this is a very high-risk group.”

She concluded that these new data “allow us to carefully select patients who can benefit from celecoxib. It should definitely be used with caution, but patients with a high risk for colon cancer and a low risk for cardiovascular disease are going to receive a significant benefit.”

“Studies such as Dr. Bertagnolli's are reinvigorating this avenue of research, with major implications for public health,” said Dr. Scott M. Lippman, professor of clinical cancer prevention at the University of Texas M.D. Anderson Cancer Center, Houston.

SAN DIEGO — Celecoxib reduced the incidence of advanced colorectal adenomas by 41% at 5 years in high-risk patients who took the controversial COX-2 inhibitor for 3 years in a cancer prevention trial before stopping it because of cardiovascular safety concerns.

“Even 2 years after we discontinued treatment with celecoxib, our patients still derived a considerable chemoprotective benefit,” Dr. Monica Bertagnolli of Brigham and Women's Hospital, Boston, said at the annual meeting of the American Association for Cancer Research.

Just as notably, Dr. Bertagnolli reported celecoxib (Celebrex) was shown to be safe in patients who had no underlying risk factors for cardiovascular disease when they entered the study.

Dr. Bertagnolli led the Adenoma Prevention With Celecoxib (APC) trial, which began enrolling patients in 1999 and was planned to run for a total of 5 years of drug treatment. Sponsored by Pfizer Inc., the study was designed to test the efficacy and safety of two doses of celecoxib in preventing colorectal adenomas in 2,035 individuals at high risk for colon cancer.

Patients who had adenomas removed before study entry were assigned to placebo (679 patients), 200 mg twice a day of celecoxib (685), or 400 mg twice a day (671) of celecoxib. They were followed with colonoscopies performed at 1 and 3 years. Just as the last patients completed 3 years of the study, the investigators recognized increased cardiovascular toxicity with celecoxib and discontinued the drug in all patients.

“At the time we began our study, the cardiovascular toxicity of celecoxib was not known. In fact, this study was the first to unveil cardiovascular disease risk with the drug. So we did not screen any of our study population for cardiovascular risk factors. Most of our patients—84%—whose median age was 60 at the time of study entry, had at least one risk factor,” Dr. Bertagnolli explained in an interview.

The efficacy results at the 3-year point were impressive, she said. Sixty percent of the placebo group had new adenomas, compared with 43% of patients receiving 200 mg of celecoxib twice a day, and 38% of those in the high-dose group receiving 400 mg of celecoxib twice a day The reduction in the rate of new advanced adenomas was even more striking at this point, with a 64% reduction at the lower dose and a 55% reduction at the higher dose of celecoxib, she noted.

Although the patients discontinued celecoxib, Dr. Bertagnolli and her colleagues decided to continue the trial as an observational study. Approximately one-third of the original randomized cohort had a colonoscopy at 5 years as planned, she said. “We kept the study going, and I'm glad we did, because now we have interesting new data,” she said.

At 5 years, with no drug on board for 1.5-2 years, the reduction in advanced lesions was 41% in the cohort who received the lower dose of celecoxib and 26% in patients who received the higher dose. There was no rebound effect—that is, lesions did not suddenly appear when the drug was stopped, Dr Bertagnolli said.

“Interestingly, the lower dose of celecoxib was the most effective at the 5-year end point,” Dr. Bertagnolli commented.

The investigators also analyzed safety, looking at any event that occurred after patients took the first dose of celecoxib up until 30 days after they took the last dose.

Cardiovascular events (myocardial infarction, stroke, peripheral vascular disease, and vascular therapeutic procedure) rose with the dose of celecoxib, occurring in 3.8% of the patients on placebo, in 6.0% of patients on the low dose of celecoxib, and in 7.5% of patients on the high dose of celecoxib.

The data showed that patients with preexisting risk factors, defined as smoking, hypertension, diabetes, hyperlipidemia, atherosclerotic heart disease, and age over 65 years, had the greatest risk:

PIFor patients with no cardiovascular risk factors before using celecoxib, the rate of cardiovascular adverse events was 0.9% in the placebo group, 3.9% in the 200-mg b.i.d. group, and 1.9% in the 400-mg b.i.d. group.

PIIf a patient had one risk factor, the rate was 2.2% in the placebo group, 3.7% in the 200-mg b.i.d. group, and 4.9% in the 400-mg b.i.d. group.

PIAmong patients who had two or more cardiovascular risk factors at the time they entered the study, those on placebo had a cardiovascular adverse event rate of 5.9%; those on 200 mg b.i.d., 8.2%; and those on 400 mg b.i.d., 11.2%.

This risk needs to be balanced with the benefit patients derived from celecoxib, Dr. Bertagnolli said. “These patients were at very high risk for colorectal adenomas. Twenty-two percent of patients on placebo got advanced adenomas during the 5 years, and over 70% of patients had adenomas that recurred if they were on placebo. So this is a very high-risk group.”

She concluded that these new data “allow us to carefully select patients who can benefit from celecoxib. It should definitely be used with caution, but patients with a high risk for colon cancer and a low risk for cardiovascular disease are going to receive a significant benefit.”

“Studies such as Dr. Bertagnolli's are reinvigorating this avenue of research, with major implications for public health,” said Dr. Scott M. Lippman, professor of clinical cancer prevention at the University of Texas M.D. Anderson Cancer Center, Houston.

SAN DIEGO — High levels of Bcl-2 in a woman's urine could be a marker for ovarian cancer.

The average amount of Bcl-2, an antiapoptotic protein that promotes cell survival, in the urine of patients with ovarian cancer was up to 10 times greater than that for healthy controls in a study reported in a poster presentation at the annual meeting of the American Association for Cancer Research.

“Measuring urinary Bcl-2 could provide a safe, specific, and economical way to detect ovarian cancer at an early, and therefore potentially curable, stage,” Dr. Patricia Kruk, of the University of South Florida, Tampa, and her coauthors suggested.

The symptoms of ovarian cancer—gas, pelvic pain, abdominal bloating—are nonspecific and are generally experienced by virtually all women from time to time.

Because these signs are so vague, most women who have ovarian cancer are diagnosed with late-stage disease, and they have a very poor prognosis, with their 5-year survival no better than 37%, Dr. Kruk explained.

“Many people will refer to this as the disease that whispers because there are no symptoms,” she said.

To validate data from an earlier pilot study that found high urinary levels of Bcl-2 were associated with ovarian cancer, Dr. Kruk and her associates obtained additional urine samples from Dr. Robert Bast of the University of Texas M.D. Anderson Cancer Center in Houston. The samples had been collected from 58 normal, healthy volunteers, 122 patients with benign gynecologic disease, and 115 patients who had ovarian cancer.

The samples were measured for Bcl-2 by enzyme-linked immunosorbent assay (ELISA).

The results of the assay showed that the average amount of Bcl-2 in the urine of the patients who had ovarian cancer was found to be greater than 2 ng/mL and up to 10 times greater than that of the healthy controls or of those patients who had benign disease.

With logistic regression, the investigators calculated that the predicted odds of cancer increased 27% with a 0.1- ng/mL increase in urinary Bcl-2 (P less than .001). Analysis of variance (ANOVA) analyses of clinical parameters indicated that the urinary levels of Bcl-2 were not significantly related to tumor size, grade, or stage.

Urinary Bcl-2 was more accurate in identifying ovarian cancer than was cancer antigen 125 (CA125), which is currently considered to be the accepted standard for ovarian cancer detection, Dr. Kruk said.

“The CA125 test is the best test we have, but it's not 100% accurate. Some people say that it ranges anywhere from 50% to 70% in accuracy and specificity, so there are a number of false positives and false negatives,” she said.

However, “we found that our urinary Bcl-2 test performs at least as well as, and in some instances even better, than the CA125 test.”

Dr. Kruk and her colleagues also reported that urinary levels of Bcl-2 decreased in ovarian cancer patients following initial debulking surgery and that it remained low while the women were receiving chemotherapy.

However, these levels increased significantly with recurrence of disease.

The urine test has been patented and has been licensed to GeoPharma Inc., she added.

“The hope is that this test will be used as part of a woman's annual physical examination, right in her doctor's office. A urine test is very simple to do, and we would expect high patient compliance, and, used either alone or in conjunction with CA125, the test might provide a better way for us to diagnose ovarian cancer,” she said.

In addition, being able to diagnose ovarian cancer at an earlier stage will save lives, Dr. Kruk said.

SAN DIEGO — High levels of Bcl-2 in a woman's urine could be a marker for ovarian cancer.

The average amount of Bcl-2, an antiapoptotic protein that promotes cell survival, in the urine of patients with ovarian cancer was up to 10 times greater than that for healthy controls in a study reported in a poster presentation at the annual meeting of the American Association for Cancer Research.

“Measuring urinary Bcl-2 could provide a safe, specific, and economical way to detect ovarian cancer at an early, and therefore potentially curable, stage,” Dr. Patricia Kruk, of the University of South Florida, Tampa, and her coauthors suggested.

The symptoms of ovarian cancer—gas, pelvic pain, abdominal bloating—are nonspecific and are generally experienced by virtually all women from time to time.

Because these signs are so vague, most women who have ovarian cancer are diagnosed with late-stage disease, and they have a very poor prognosis, with their 5-year survival no better than 37%, Dr. Kruk explained.

“Many people will refer to this as the disease that whispers because there are no symptoms,” she said.

To validate data from an earlier pilot study that found high urinary levels of Bcl-2 were associated with ovarian cancer, Dr. Kruk and her associates obtained additional urine samples from Dr. Robert Bast of the University of Texas M.D. Anderson Cancer Center in Houston. The samples had been collected from 58 normal, healthy volunteers, 122 patients with benign gynecologic disease, and 115 patients who had ovarian cancer.

The samples were measured for Bcl-2 by enzyme-linked immunosorbent assay (ELISA).

The results of the assay showed that the average amount of Bcl-2 in the urine of the patients who had ovarian cancer was found to be greater than 2 ng/mL and up to 10 times greater than that of the healthy controls or of those patients who had benign disease.

With logistic regression, the investigators calculated that the predicted odds of cancer increased 27% with a 0.1- ng/mL increase in urinary Bcl-2 (P less than .001). Analysis of variance (ANOVA) analyses of clinical parameters indicated that the urinary levels of Bcl-2 were not significantly related to tumor size, grade, or stage.

Urinary Bcl-2 was more accurate in identifying ovarian cancer than was cancer antigen 125 (CA125), which is currently considered to be the accepted standard for ovarian cancer detection, Dr. Kruk said.

“The CA125 test is the best test we have, but it's not 100% accurate. Some people say that it ranges anywhere from 50% to 70% in accuracy and specificity, so there are a number of false positives and false negatives,” she said.

However, “we found that our urinary Bcl-2 test performs at least as well as, and in some instances even better, than the CA125 test.”

Dr. Kruk and her colleagues also reported that urinary levels of Bcl-2 decreased in ovarian cancer patients following initial debulking surgery and that it remained low while the women were receiving chemotherapy.

However, these levels increased significantly with recurrence of disease.

The urine test has been patented and has been licensed to GeoPharma Inc., she added.

“The hope is that this test will be used as part of a woman's annual physical examination, right in her doctor's office. A urine test is very simple to do, and we would expect high patient compliance, and, used either alone or in conjunction with CA125, the test might provide a better way for us to diagnose ovarian cancer,” she said.

In addition, being able to diagnose ovarian cancer at an earlier stage will save lives, Dr. Kruk said.

SAN DIEGO — High levels of Bcl-2 in a woman's urine could be a marker for ovarian cancer.

The average amount of Bcl-2, an antiapoptotic protein that promotes cell survival, in the urine of patients with ovarian cancer was up to 10 times greater than that for healthy controls in a study reported in a poster presentation at the annual meeting of the American Association for Cancer Research.

“Measuring urinary Bcl-2 could provide a safe, specific, and economical way to detect ovarian cancer at an early, and therefore potentially curable, stage,” Dr. Patricia Kruk, of the University of South Florida, Tampa, and her coauthors suggested.

The symptoms of ovarian cancer—gas, pelvic pain, abdominal bloating—are nonspecific and are generally experienced by virtually all women from time to time.

Because these signs are so vague, most women who have ovarian cancer are diagnosed with late-stage disease, and they have a very poor prognosis, with their 5-year survival no better than 37%, Dr. Kruk explained.

“Many people will refer to this as the disease that whispers because there are no symptoms,” she said.

To validate data from an earlier pilot study that found high urinary levels of Bcl-2 were associated with ovarian cancer, Dr. Kruk and her associates obtained additional urine samples from Dr. Robert Bast of the University of Texas M.D. Anderson Cancer Center in Houston. The samples had been collected from 58 normal, healthy volunteers, 122 patients with benign gynecologic disease, and 115 patients who had ovarian cancer.

The samples were measured for Bcl-2 by enzyme-linked immunosorbent assay (ELISA).

The results of the assay showed that the average amount of Bcl-2 in the urine of the patients who had ovarian cancer was found to be greater than 2 ng/mL and up to 10 times greater than that of the healthy controls or of those patients who had benign disease.

With logistic regression, the investigators calculated that the predicted odds of cancer increased 27% with a 0.1- ng/mL increase in urinary Bcl-2 (P less than .001). Analysis of variance (ANOVA) analyses of clinical parameters indicated that the urinary levels of Bcl-2 were not significantly related to tumor size, grade, or stage.

Urinary Bcl-2 was more accurate in identifying ovarian cancer than was cancer antigen 125 (CA125), which is currently considered to be the accepted standard for ovarian cancer detection, Dr. Kruk said.

“The CA125 test is the best test we have, but it's not 100% accurate. Some people say that it ranges anywhere from 50% to 70% in accuracy and specificity, so there are a number of false positives and false negatives,” she said.

However, “we found that our urinary Bcl-2 test performs at least as well as, and in some instances even better, than the CA125 test.”

Dr. Kruk and her colleagues also reported that urinary levels of Bcl-2 decreased in ovarian cancer patients following initial debulking surgery and that it remained low while the women were receiving chemotherapy.

However, these levels increased significantly with recurrence of disease.

The urine test has been patented and has been licensed to GeoPharma Inc., she added.

“The hope is that this test will be used as part of a woman's annual physical examination, right in her doctor's office. A urine test is very simple to do, and we would expect high patient compliance, and, used either alone or in conjunction with CA125, the test might provide a better way for us to diagnose ovarian cancer,” she said.

In addition, being able to diagnose ovarian cancer at an earlier stage will save lives, Dr. Kruk said.

HOLLYWOOD, FLA. — Advances in the treatment of breast cancer have been significant, but they have come at a price: increased toxicity to the heart. The most important step in minimizing this cardiotoxicity is to be aware that it does occur, Dr. William J. Gradishar said at the annual conference of the National Comprehensive Cancer Network.

“Women with breast cancer are living longer and, as time passes, some of the long-term side effects as a result of therapy may become apparent. That is certainly an issue with some of the systemic therapies we use,” said Dr. Gradishar, professor of medicine at Northwestern University, Chicago.

Factors that may raise the risk of cardiotoxicity include age, with women aged 70 years and older at particularly high risk; mediastinal radiotherapy; and preexisting heart disease.

Dr. Gradishar said outcomes for patients receiving radiation have improved over the past 10 years, largely because of better planning and technology. However, while this has occurred, there has been an increase in non-breast cancer mortality, and heart disease has risen by 27%. He cautioned that clinicians must recognize that there is a small but real risk of cardiac side effects related to radiation therapy, particularly when it is left sided. “We have to balance this risk against the incremental improvement in outcome that comes with adjuvant radiation therapy.”

Dr. Gradishar also talked about the perils of systemic therapy. Here, the anthracyclines, most notably doxorubicin, are the main cardiotoxicity culprits. Doxorubicin lowers left ventricular ejection fraction, and some patients develop heart failure as a result. Dr. Gradishar said these drops in ejection fraction can be asymptomatic.

Treatment with ACE inhibitors and calcium channel blockers can help these patients recover their cardiac function, but left to its own devices, anthracycline-induced heart failure will not resolve spontaneously, he said.

Dexrazoxane (Zinecard, Pfizer Inc.) is an iron chelator that counteracts the cardiotoxic effects of the anthracyclines. It is approved for reducing the incidence and severity of doxorubicin-associated cardiomyopathy in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m

“There was concern that dexrazoxane might attenuate some of the antitumor effect of the doxorubicin if it was started from the get-go as opposed to starting it later. So for those patients you think would benefit from doxorubicin beyond 300 mg/m

More recently, concerns have been raised about the cardiotoxicity of targeted therapy with trastuzumab. This risk is justified, given the dramatic 25% improvement in overall survival in poor prognosis HER2-positive breast cancer seen with the drug, Dr. Gradishar said.

He noted that about 4% of patients getting chemotherapy with concurrent trastuzumab develop heart failure. “Most of the events occur relatively early on so we are not seeing—at least with the follow-up we have to date—a large spike in [heart failure] after therapy is discontinued,” he said, adding most of the cardiac toxicity occurs in the midst of therapy.

Predicting who will develop cardiac problems from their therapy remains difficult. Symptoms are not the most sensitive way of detecting or predicting who is going to have a problem, Dr. Gradishar said.

Similarly, electrocardiographic changes are not always predictive, he said.

Biomarkers such as troponin and brain natriuretic peptide are being investigated as indicators of developing cardiotoxicity or cardiovascular risk but are not standard of care, Dr. Gradishar said. He stated that he had no conflicts of interest to declare.

As time passes, some of the long-term side effects of breast cancer therapy may become apparent. DR. GRADISHAR

HOLLYWOOD, FLA. — Advances in the treatment of breast cancer have been significant, but they have come at a price: increased toxicity to the heart. The most important step in minimizing this cardiotoxicity is to be aware that it does occur, Dr. William J. Gradishar said at the annual conference of the National Comprehensive Cancer Network.

“Women with breast cancer are living longer and, as time passes, some of the long-term side effects as a result of therapy may become apparent. That is certainly an issue with some of the systemic therapies we use,” said Dr. Gradishar, professor of medicine at Northwestern University, Chicago.

Factors that may raise the risk of cardiotoxicity include age, with women aged 70 years and older at particularly high risk; mediastinal radiotherapy; and preexisting heart disease.

Dr. Gradishar said outcomes for patients receiving radiation have improved over the past 10 years, largely because of better planning and technology. However, while this has occurred, there has been an increase in non-breast cancer mortality, and heart disease has risen by 27%. He cautioned that clinicians must recognize that there is a small but real risk of cardiac side effects related to radiation therapy, particularly when it is left sided. “We have to balance this risk against the incremental improvement in outcome that comes with adjuvant radiation therapy.”

Dr. Gradishar also talked about the perils of systemic therapy. Here, the anthracyclines, most notably doxorubicin, are the main cardiotoxicity culprits. Doxorubicin lowers left ventricular ejection fraction, and some patients develop heart failure as a result. Dr. Gradishar said these drops in ejection fraction can be asymptomatic.

Treatment with ACE inhibitors and calcium channel blockers can help these patients recover their cardiac function, but left to its own devices, anthracycline-induced heart failure will not resolve spontaneously, he said.

Dexrazoxane (Zinecard, Pfizer Inc.) is an iron chelator that counteracts the cardiotoxic effects of the anthracyclines. It is approved for reducing the incidence and severity of doxorubicin-associated cardiomyopathy in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m

“There was concern that dexrazoxane might attenuate some of the antitumor effect of the doxorubicin if it was started from the get-go as opposed to starting it later. So for those patients you think would benefit from doxorubicin beyond 300 mg/m

More recently, concerns have been raised about the cardiotoxicity of targeted therapy with trastuzumab. This risk is justified, given the dramatic 25% improvement in overall survival in poor prognosis HER2-positive breast cancer seen with the drug, Dr. Gradishar said.

He noted that about 4% of patients getting chemotherapy with concurrent trastuzumab develop heart failure. “Most of the events occur relatively early on so we are not seeing—at least with the follow-up we have to date—a large spike in [heart failure] after therapy is discontinued,” he said, adding most of the cardiac toxicity occurs in the midst of therapy.

Predicting who will develop cardiac problems from their therapy remains difficult. Symptoms are not the most sensitive way of detecting or predicting who is going to have a problem, Dr. Gradishar said.

Similarly, electrocardiographic changes are not always predictive, he said.

Biomarkers such as troponin and brain natriuretic peptide are being investigated as indicators of developing cardiotoxicity or cardiovascular risk but are not standard of care, Dr. Gradishar said. He stated that he had no conflicts of interest to declare.

As time passes, some of the long-term side effects of breast cancer therapy may become apparent. DR. GRADISHAR

HOLLYWOOD, FLA. — Advances in the treatment of breast cancer have been significant, but they have come at a price: increased toxicity to the heart. The most important step in minimizing this cardiotoxicity is to be aware that it does occur, Dr. William J. Gradishar said at the annual conference of the National Comprehensive Cancer Network.

“Women with breast cancer are living longer and, as time passes, some of the long-term side effects as a result of therapy may become apparent. That is certainly an issue with some of the systemic therapies we use,” said Dr. Gradishar, professor of medicine at Northwestern University, Chicago.

Factors that may raise the risk of cardiotoxicity include age, with women aged 70 years and older at particularly high risk; mediastinal radiotherapy; and preexisting heart disease.

Dr. Gradishar said outcomes for patients receiving radiation have improved over the past 10 years, largely because of better planning and technology. However, while this has occurred, there has been an increase in non-breast cancer mortality, and heart disease has risen by 27%. He cautioned that clinicians must recognize that there is a small but real risk of cardiac side effects related to radiation therapy, particularly when it is left sided. “We have to balance this risk against the incremental improvement in outcome that comes with adjuvant radiation therapy.”

Dr. Gradishar also talked about the perils of systemic therapy. Here, the anthracyclines, most notably doxorubicin, are the main cardiotoxicity culprits. Doxorubicin lowers left ventricular ejection fraction, and some patients develop heart failure as a result. Dr. Gradishar said these drops in ejection fraction can be asymptomatic.

Treatment with ACE inhibitors and calcium channel blockers can help these patients recover their cardiac function, but left to its own devices, anthracycline-induced heart failure will not resolve spontaneously, he said.

Dexrazoxane (Zinecard, Pfizer Inc.) is an iron chelator that counteracts the cardiotoxic effects of the anthracyclines. It is approved for reducing the incidence and severity of doxorubicin-associated cardiomyopathy in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m

“There was concern that dexrazoxane might attenuate some of the antitumor effect of the doxorubicin if it was started from the get-go as opposed to starting it later. So for those patients you think would benefit from doxorubicin beyond 300 mg/m

More recently, concerns have been raised about the cardiotoxicity of targeted therapy with trastuzumab. This risk is justified, given the dramatic 25% improvement in overall survival in poor prognosis HER2-positive breast cancer seen with the drug, Dr. Gradishar said.

He noted that about 4% of patients getting chemotherapy with concurrent trastuzumab develop heart failure. “Most of the events occur relatively early on so we are not seeing—at least with the follow-up we have to date—a large spike in [heart failure] after therapy is discontinued,” he said, adding most of the cardiac toxicity occurs in the midst of therapy.

Predicting who will develop cardiac problems from their therapy remains difficult. Symptoms are not the most sensitive way of detecting or predicting who is going to have a problem, Dr. Gradishar said.

Similarly, electrocardiographic changes are not always predictive, he said.

Biomarkers such as troponin and brain natriuretic peptide are being investigated as indicators of developing cardiotoxicity or cardiovascular risk but are not standard of care, Dr. Gradishar said. He stated that he had no conflicts of interest to declare.

As time passes, some of the long-term side effects of breast cancer therapy may become apparent. DR. GRADISHAR

HOLLYWOOD, FLA. — Updated National Comprehensive Cancer Network guidelines stress expectant management—surveillance only with no other treatment—for low- and intermediate-risk prostate cancer.

“We think it is more prudent to take into account a man's life expectancy than just to look at his prostate cancer when it comes to devising a treatment strategy,” Dr. James L. Mohler, chairman of the department of urologic oncology at Roswell Park Cancer Institute, Buffalo, N.Y., said at the NCCN's annual conference.

The NCCN prostate cancer guidelines now recommend that men with low-risk prostate cancer (stage T1-T2a, Gleason score 2–6, and prostate specific antigen (PSA) levels less than 10 ng/mL) consider expectant management, regardless of whether their life expectancy is more or less than 10 years.

If these low-risk men decline expectant management, the NCCN recommends radiation therapy with three-dimensional conformal radiation, intensity-modulated radiation, or brachytherapy if their life expectancy is less than 10 years. If their life expectancy is more than 10 years, the guidelines stipulate an additional option: radical prostatectomy with or without pelvic lymph node dissection if the predicted probability of lymph node metastasis is 7% or greater.

Expectant management is also an option for men with intermediate-risk prostate cancer (stage 2b-T2c, Gleason score 7, and PSA levels of 10–20 ng/mL).

“Increased emphasis on expectant management as an appropriate option … is the most interesting change in the [guidelines],” said Dr. Mohler, who chaired the NCCN prostate cancer guidelines committee.

Also new is a warning against the use of neoadjuvant androgen deprivation therapy before radical prostatectomy. “It does not work, and it makes the operation more difficult,” he said.

The panel also stated that radical prostatectomy may be performed as an open procedure, laparoscopically, or as a robot-assisted procedure. In addition, patients should consider high-volume surgeons and high-volume centers when opting for radical prostatectomy, “because, in general, the procedures will be performed better.”

Robot-assisted prostatectomy was added to the new guidelines, Dr. Mohler said, because it offers the same results as open or laparoscopically performed surgery with faster recovery times. Any dangerous movements are recognized as “not allowed” by the robot. In addition, complex maneuvers such as suturing and tying knots also can be performed easily. “The patients I do every Monday go home Tuesday at 2 o'clock.”

Dr. Mohler said he had no conflicts of interest to declare.

The patient shown here has undergone a radical prostatectomy using robotic surgery, which Dr. Mohler referred to as 'the new look of the surgical urologic oncology patient.' Courtesy Roswell Park Cancer Institute

The guidelines now include robotic prostatectomy because it issafer, faster, easier, and has good outcomes. DR. MOHLER

HOLLYWOOD, FLA. — Updated National Comprehensive Cancer Network guidelines stress expectant management—surveillance only with no other treatment—for low- and intermediate-risk prostate cancer.

“We think it is more prudent to take into account a man's life expectancy than just to look at his prostate cancer when it comes to devising a treatment strategy,” Dr. James L. Mohler, chairman of the department of urologic oncology at Roswell Park Cancer Institute, Buffalo, N.Y., said at the NCCN's annual conference.

The NCCN prostate cancer guidelines now recommend that men with low-risk prostate cancer (stage T1-T2a, Gleason score 2–6, and prostate specific antigen (PSA) levels less than 10 ng/mL) consider expectant management, regardless of whether their life expectancy is more or less than 10 years.

If these low-risk men decline expectant management, the NCCN recommends radiation therapy with three-dimensional conformal radiation, intensity-modulated radiation, or brachytherapy if their life expectancy is less than 10 years. If their life expectancy is more than 10 years, the guidelines stipulate an additional option: radical prostatectomy with or without pelvic lymph node dissection if the predicted probability of lymph node metastasis is 7% or greater.

Expectant management is also an option for men with intermediate-risk prostate cancer (stage 2b-T2c, Gleason score 7, and PSA levels of 10–20 ng/mL).

“Increased emphasis on expectant management as an appropriate option … is the most interesting change in the [guidelines],” said Dr. Mohler, who chaired the NCCN prostate cancer guidelines committee.

Also new is a warning against the use of neoadjuvant androgen deprivation therapy before radical prostatectomy. “It does not work, and it makes the operation more difficult,” he said.

The panel also stated that radical prostatectomy may be performed as an open procedure, laparoscopically, or as a robot-assisted procedure. In addition, patients should consider high-volume surgeons and high-volume centers when opting for radical prostatectomy, “because, in general, the procedures will be performed better.”

Robot-assisted prostatectomy was added to the new guidelines, Dr. Mohler said, because it offers the same results as open or laparoscopically performed surgery with faster recovery times. Any dangerous movements are recognized as “not allowed” by the robot. In addition, complex maneuvers such as suturing and tying knots also can be performed easily. “The patients I do every Monday go home Tuesday at 2 o'clock.”

Dr. Mohler said he had no conflicts of interest to declare.

The patient shown here has undergone a radical prostatectomy using robotic surgery, which Dr. Mohler referred to as 'the new look of the surgical urologic oncology patient.' Courtesy Roswell Park Cancer Institute

The guidelines now include robotic prostatectomy because it issafer, faster, easier, and has good outcomes. DR. MOHLER

HOLLYWOOD, FLA. — Updated National Comprehensive Cancer Network guidelines stress expectant management—surveillance only with no other treatment—for low- and intermediate-risk prostate cancer.

“We think it is more prudent to take into account a man's life expectancy than just to look at his prostate cancer when it comes to devising a treatment strategy,” Dr. James L. Mohler, chairman of the department of urologic oncology at Roswell Park Cancer Institute, Buffalo, N.Y., said at the NCCN's annual conference.

The NCCN prostate cancer guidelines now recommend that men with low-risk prostate cancer (stage T1-T2a, Gleason score 2–6, and prostate specific antigen (PSA) levels less than 10 ng/mL) consider expectant management, regardless of whether their life expectancy is more or less than 10 years.

If these low-risk men decline expectant management, the NCCN recommends radiation therapy with three-dimensional conformal radiation, intensity-modulated radiation, or brachytherapy if their life expectancy is less than 10 years. If their life expectancy is more than 10 years, the guidelines stipulate an additional option: radical prostatectomy with or without pelvic lymph node dissection if the predicted probability of lymph node metastasis is 7% or greater.

Expectant management is also an option for men with intermediate-risk prostate cancer (stage 2b-T2c, Gleason score 7, and PSA levels of 10–20 ng/mL).

“Increased emphasis on expectant management as an appropriate option … is the most interesting change in the [guidelines],” said Dr. Mohler, who chaired the NCCN prostate cancer guidelines committee.

Also new is a warning against the use of neoadjuvant androgen deprivation therapy before radical prostatectomy. “It does not work, and it makes the operation more difficult,” he said.

The panel also stated that radical prostatectomy may be performed as an open procedure, laparoscopically, or as a robot-assisted procedure. In addition, patients should consider high-volume surgeons and high-volume centers when opting for radical prostatectomy, “because, in general, the procedures will be performed better.”

Robot-assisted prostatectomy was added to the new guidelines, Dr. Mohler said, because it offers the same results as open or laparoscopically performed surgery with faster recovery times. Any dangerous movements are recognized as “not allowed” by the robot. In addition, complex maneuvers such as suturing and tying knots also can be performed easily. “The patients I do every Monday go home Tuesday at 2 o'clock.”

Dr. Mohler said he had no conflicts of interest to declare.

The patient shown here has undergone a radical prostatectomy using robotic surgery, which Dr. Mohler referred to as 'the new look of the surgical urologic oncology patient.' Courtesy Roswell Park Cancer Institute

The guidelines now include robotic prostatectomy because it issafer, faster, easier, and has good outcomes. DR. MOHLER

HOLLYWOOD, FLA. — The use of three-dimensional conformal radiation or intensity-modulated radiation therapy is now mandated in the National Comprehensive Cancer Network's new treatment guidelines for prostate cancer.

Specific recommendations for radiation doses to treat low-, intermediate-, and high-risk prostate cancer have also been added.

“Our decisions are not black and white, and most patients will have multiple options regarding which treatment they wish to pursue,” Dr. Michael R. Kuettel, professor and chair of radiation medicine at Roswell Park Cancer Center, Buffalo, N.Y., said at the NCCN's annual conference.

Risk stratification is extremely important. Past guidelines have included stage, Gleason score, and prostate-specific antigen levels. This year, estimates of a patient's life expectancy have been added to calculate overall risk, said Dr. Kuettel, who is also president-elect of the American College of Radiation Oncology.

As disease risk increases, so should the dose of radiation. For patients with low-risk disease, the guidelines recommend radiation doses of 70–79 Gy and no radiation to the lymph nodes. For intermediate or high risk, the recommendation is for radiation doses of 75–80 Gy, with consideration of pelvic lymph node external beam radiation therapy or androgen deprivation therapy.

Increasing the dose of radiation produces better outcomes, but it also has the potential for increasing side effects, said Dr. Kuettel. One way to minimize radiation toxicity is to use three-dimensional conformal radiation or intensity-modulated radiation therapy. Another is to locate the position of the prostate on a daily basis.

“With dose escalation, one needs to confine the dose very precisely and to do that you need to know where the prostate is on a day-to-day basis,” he said. “Now that we can paint the dose wherever we want at practically any intensity that we want, the weakest link in the treatment chain is locating the target.”

The position of the prostate can vary as much as 2 centimeters in any one direction for a number of reasons, including changes in body weight, whether the bladder or rectum is empty or full, and organ motion due to respiration, cardiac and bowel motion, swallowing, and other movements while the patient is on the imaging table.

He disclosed that he had no relevant financial conflicts of interest to declare.

'Most patients will have multiple options regarding which treatment they wish to pursue.' DR. KUETTEL

HOLLYWOOD, FLA. — The use of three-dimensional conformal radiation or intensity-modulated radiation therapy is now mandated in the National Comprehensive Cancer Network's new treatment guidelines for prostate cancer.

Specific recommendations for radiation doses to treat low-, intermediate-, and high-risk prostate cancer have also been added.

“Our decisions are not black and white, and most patients will have multiple options regarding which treatment they wish to pursue,” Dr. Michael R. Kuettel, professor and chair of radiation medicine at Roswell Park Cancer Center, Buffalo, N.Y., said at the NCCN's annual conference.

Risk stratification is extremely important. Past guidelines have included stage, Gleason score, and prostate-specific antigen levels. This year, estimates of a patient's life expectancy have been added to calculate overall risk, said Dr. Kuettel, who is also president-elect of the American College of Radiation Oncology.

As disease risk increases, so should the dose of radiation. For patients with low-risk disease, the guidelines recommend radiation doses of 70–79 Gy and no radiation to the lymph nodes. For intermediate or high risk, the recommendation is for radiation doses of 75–80 Gy, with consideration of pelvic lymph node external beam radiation therapy or androgen deprivation therapy.

Increasing the dose of radiation produces better outcomes, but it also has the potential for increasing side effects, said Dr. Kuettel. One way to minimize radiation toxicity is to use three-dimensional conformal radiation or intensity-modulated radiation therapy. Another is to locate the position of the prostate on a daily basis.

“With dose escalation, one needs to confine the dose very precisely and to do that you need to know where the prostate is on a day-to-day basis,” he said. “Now that we can paint the dose wherever we want at practically any intensity that we want, the weakest link in the treatment chain is locating the target.”

The position of the prostate can vary as much as 2 centimeters in any one direction for a number of reasons, including changes in body weight, whether the bladder or rectum is empty or full, and organ motion due to respiration, cardiac and bowel motion, swallowing, and other movements while the patient is on the imaging table.

He disclosed that he had no relevant financial conflicts of interest to declare.

'Most patients will have multiple options regarding which treatment they wish to pursue.' DR. KUETTEL

HOLLYWOOD, FLA. — The use of three-dimensional conformal radiation or intensity-modulated radiation therapy is now mandated in the National Comprehensive Cancer Network's new treatment guidelines for prostate cancer.

Specific recommendations for radiation doses to treat low-, intermediate-, and high-risk prostate cancer have also been added.

“Our decisions are not black and white, and most patients will have multiple options regarding which treatment they wish to pursue,” Dr. Michael R. Kuettel, professor and chair of radiation medicine at Roswell Park Cancer Center, Buffalo, N.Y., said at the NCCN's annual conference.

Risk stratification is extremely important. Past guidelines have included stage, Gleason score, and prostate-specific antigen levels. This year, estimates of a patient's life expectancy have been added to calculate overall risk, said Dr. Kuettel, who is also president-elect of the American College of Radiation Oncology.

As disease risk increases, so should the dose of radiation. For patients with low-risk disease, the guidelines recommend radiation doses of 70–79 Gy and no radiation to the lymph nodes. For intermediate or high risk, the recommendation is for radiation doses of 75–80 Gy, with consideration of pelvic lymph node external beam radiation therapy or androgen deprivation therapy.

Increasing the dose of radiation produces better outcomes, but it also has the potential for increasing side effects, said Dr. Kuettel. One way to minimize radiation toxicity is to use three-dimensional conformal radiation or intensity-modulated radiation therapy. Another is to locate the position of the prostate on a daily basis.

“With dose escalation, one needs to confine the dose very precisely and to do that you need to know where the prostate is on a day-to-day basis,” he said. “Now that we can paint the dose wherever we want at practically any intensity that we want, the weakest link in the treatment chain is locating the target.”

The position of the prostate can vary as much as 2 centimeters in any one direction for a number of reasons, including changes in body weight, whether the bladder or rectum is empty or full, and organ motion due to respiration, cardiac and bowel motion, swallowing, and other movements while the patient is on the imaging table.

He disclosed that he had no relevant financial conflicts of interest to declare.

'Most patients will have multiple options regarding which treatment they wish to pursue.' DR. KUETTEL