Fran Lowry

NEW ORLEANS — Combination therapy with bupropion and naltrexone resulted in superior weight loss, compared with placebo or either drug alone, Dr. Frank L. Greenway said at the annual meeting of NAASO, the Obesity Society.

Patients randomized to the experimental bupropion-naltrexone combination achieved a 1.5- to twofold greater weight loss after 24 weeks of treatment than did those randomized to monotherapy with bupropion or naltrexone, or to placebo.

The combination patients also achieved a greater improvement in insulin resistance and markers of cardiovascular disease risk, such as waist circumference and triglyceride levels, said Dr. Greenway, chief of the outpatient clinic at Louisiana State University's Pennington Biomedical Research Center, Baton Rouge.

The multicenter trial randomized 419 healthy, nondiabetic obese subjects to receive 200 mg bupropion twice a day; 48 mg naltrexone once a day; 200 mg bupropion combined with 16, 32, or 48 mg naltrexone twice a day; or placebo. The patients also received an exercise prescription and were placed on a diet.

A subset of 75 randomized subjects had a DEXA scan to measure body fat, and 73 randomized subjects had a multislice abdominal CT scan to measure visceral fat. The measures were taken at baseline and at 24 weeks, as were insulin, glucose, and triglyceride analyses. Patients treated with the bupropion-naltrexone combination showed a statistically significant greater total body weight loss, compared with placebo or monotherapy subjects. Orexigen Therapeutics Inc., San Diego, provided the combination drug.

The greatest weight loss effect was observed for the combination that included naltrexone at the dose of 32 mg, he said. Subjects randomized to that regimen lost a mean of 7% of their body weight, 12% of their body fat, and 14% of their visceral fat. Waist circumference also was reduced by a mean of 5.4 cm.

In addition, their insulin levels declined by a mean of 3 mcU/mL, fasting glucose fell by a mean of 2 mg/dL, and triglyceride levels fell by a mean of 44 mg/dL, all of which were statistically significantly greater than the values for the other regimens.

The naltrexone-bupropion combination promotes hypothalamic proopiomelano-cortin activity, which reduces appetite and stimulates energy expenditure, thereby preventing an early plateau or slowing down of weight loss.

Bupropion and naltrexone have been approved by the Food and Drug Administration for treating addictive disorders, but the combined formulation has not been approved. “We expect the new [combination] drug application to be submitted in 2009,” said Dr. Greenway, who disclosed that he is a consultant for Orexigen Therapeutics.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Combination therapy with bupropion and naltrexone resulted in superior weight loss, compared with placebo or either drug alone, Dr. Frank L. Greenway said at the annual meeting of NAASO, the Obesity Society.

Patients randomized to the experimental bupropion-naltrexone combination achieved a 1.5- to twofold greater weight loss after 24 weeks of treatment than did those randomized to monotherapy with bupropion or naltrexone, or to placebo.

The combination patients also achieved a greater improvement in insulin resistance and markers of cardiovascular disease risk, such as waist circumference and triglyceride levels, said Dr. Greenway, chief of the outpatient clinic at Louisiana State University's Pennington Biomedical Research Center, Baton Rouge.

The multicenter trial randomized 419 healthy, nondiabetic obese subjects to receive 200 mg bupropion twice a day; 48 mg naltrexone once a day; 200 mg bupropion combined with 16, 32, or 48 mg naltrexone twice a day; or placebo. The patients also received an exercise prescription and were placed on a diet.

A subset of 75 randomized subjects had a DEXA scan to measure body fat, and 73 randomized subjects had a multislice abdominal CT scan to measure visceral fat. The measures were taken at baseline and at 24 weeks, as were insulin, glucose, and triglyceride analyses. Patients treated with the bupropion-naltrexone combination showed a statistically significant greater total body weight loss, compared with placebo or monotherapy subjects. Orexigen Therapeutics Inc., San Diego, provided the combination drug.

The greatest weight loss effect was observed for the combination that included naltrexone at the dose of 32 mg, he said. Subjects randomized to that regimen lost a mean of 7% of their body weight, 12% of their body fat, and 14% of their visceral fat. Waist circumference also was reduced by a mean of 5.4 cm.

In addition, their insulin levels declined by a mean of 3 mcU/mL, fasting glucose fell by a mean of 2 mg/dL, and triglyceride levels fell by a mean of 44 mg/dL, all of which were statistically significantly greater than the values for the other regimens.

The naltrexone-bupropion combination promotes hypothalamic proopiomelano-cortin activity, which reduces appetite and stimulates energy expenditure, thereby preventing an early plateau or slowing down of weight loss.

Bupropion and naltrexone have been approved by the Food and Drug Administration for treating addictive disorders, but the combined formulation has not been approved. “We expect the new [combination] drug application to be submitted in 2009,” said Dr. Greenway, who disclosed that he is a consultant for Orexigen Therapeutics.

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Combination therapy with bupropion and naltrexone resulted in superior weight loss, compared with placebo or either drug alone, Dr. Frank L. Greenway said at the annual meeting of NAASO, the Obesity Society.

Patients randomized to the experimental bupropion-naltrexone combination achieved a 1.5- to twofold greater weight loss after 24 weeks of treatment than did those randomized to monotherapy with bupropion or naltrexone, or to placebo.

The combination patients also achieved a greater improvement in insulin resistance and markers of cardiovascular disease risk, such as waist circumference and triglyceride levels, said Dr. Greenway, chief of the outpatient clinic at Louisiana State University's Pennington Biomedical Research Center, Baton Rouge.

The multicenter trial randomized 419 healthy, nondiabetic obese subjects to receive 200 mg bupropion twice a day; 48 mg naltrexone once a day; 200 mg bupropion combined with 16, 32, or 48 mg naltrexone twice a day; or placebo. The patients also received an exercise prescription and were placed on a diet.

A subset of 75 randomized subjects had a DEXA scan to measure body fat, and 73 randomized subjects had a multislice abdominal CT scan to measure visceral fat. The measures were taken at baseline and at 24 weeks, as were insulin, glucose, and triglyceride analyses. Patients treated with the bupropion-naltrexone combination showed a statistically significant greater total body weight loss, compared with placebo or monotherapy subjects. Orexigen Therapeutics Inc., San Diego, provided the combination drug.

The greatest weight loss effect was observed for the combination that included naltrexone at the dose of 32 mg, he said. Subjects randomized to that regimen lost a mean of 7% of their body weight, 12% of their body fat, and 14% of their visceral fat. Waist circumference also was reduced by a mean of 5.4 cm.

In addition, their insulin levels declined by a mean of 3 mcU/mL, fasting glucose fell by a mean of 2 mg/dL, and triglyceride levels fell by a mean of 44 mg/dL, all of which were statistically significantly greater than the values for the other regimens.

The naltrexone-bupropion combination promotes hypothalamic proopiomelano-cortin activity, which reduces appetite and stimulates energy expenditure, thereby preventing an early plateau or slowing down of weight loss.

Bupropion and naltrexone have been approved by the Food and Drug Administration for treating addictive disorders, but the combined formulation has not been approved. “We expect the new [combination] drug application to be submitted in 2009,” said Dr. Greenway, who disclosed that he is a consultant for Orexigen Therapeutics.

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Colorectal cancer screening plays an important role in cancer prevention and detection, not just in the “young-old,” but also in the “old-old”–people in their eighties and beyond.

And if a cancer is found, the elderly can also derive considerable benefit from treatments including surgery and chemotherapy, two presenters said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

A retrospective review of 1,390 patients aged 80 years and older who were screened with colonoscopy at Mount Sinai Medical Center in Miami Beach, Fla., during the last 26 years showed that the majority of cancers (74%) were caught at an early stage when they were treatable by surgery alone, Dr. Heloisa P. Soares said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Treatment with chemotherapy for more advanced colon cancer was also beneficial in this elderly population, whose mean age at diagnosis was 85 years, Dr. Soares said.

In all, 98 patients received chemotherapy as part of their treatment. In patients with stage II colon cancer, chemotherapy resulted in a median overall survival of 75 months, compared with 46 months for patients treated with surgery alone. In stage III colon cancer, chemotherapy likewise improved survival, to 49 months vs. 25 months for surgery alone. However, in stage IV colon cancer, survival was similar: 9 months with and 8 months without chemotherapy.

“More than 70% of newly diagnosed colon cancer cases are in people older than 70 years. Screening in this population pays off, and so does chemotherapy, especially in the early stages,” Dr. Soares said.

In another study presented at the meeting, 161 metastatic colorectal cancer patients aged 80 years or older who were treated with bevacizumab (Avastin) and standard chemotherapy tolerated the regimen as well as their younger counterparts aged 65–79 years, and also had the same progression-free survival. After a median follow-up of 21 months, the median progression-free survival was 10 months for all patients, regardless of their age. The only risk factors for poor outcome were poor performance status (defined as ECOG [Eastern Cooperative Oncology Group] performance status of grade 2 or greater) and a history of arterial thrombotic events.

These results, from the BRITE (Bevacizumab Regimens Investigation of Treatment Effects and Safety) prospective cohort study, show that advanced age in itself should not be considered a deterrent to treating patients, said Dr. Mark Kozloff of Ingalls Memorial Hospital, Harvey, Ill., and the University of Chicago.

BRITE's cohort of elderly metastatic colorectal cancer patients offers the opportunity to analyze bevacizumab and chemotherapy treatment outcomes in a population that is poorly represented in clinical trials, he said in an interview. “These were all comers, unselected patients with metastatic colorectal cancer who are age 65 and older, and just those patients that we encounter most often in our real-world clinical practices. So these data are reassuring.”

Bevacizumab has been shown to prolong overall survival and progression-free survival when added to chemotherapy for metastatic colorectal cancer, but it is associated with an increase in arterial thromboembolic events. Of 1,953 patients in the observational cohort, 896 patients were aged 65–74 years, 533 were aged 75–79 years, and the rest were aged 80 years or older.

There was a lower median overall survival for patients aged 80 years and older (16 months vs. 21 months for patients aged 65–74, and 20 months for patients aged 75–79) but this might be because of less aggressive treatment in this older cohort, he said. Side effects with bevacizumab were similar across all age groups.

Dr. Soares disclosed no conflicts of interest. Dr. Kozloff said he receives research funding from Genentech Inc. which developed Avastin and sponsored BRITE.

'Screening in this population pays off, and so does chemotherapy, especially in the early stages.' DR. SOARES

ORLANDO — Colorectal cancer screening plays an important role in cancer prevention and detection, not just in the “young-old,” but also in the “old-old”–people in their eighties and beyond.

And if a cancer is found, the elderly can also derive considerable benefit from treatments including surgery and chemotherapy, two presenters said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

A retrospective review of 1,390 patients aged 80 years and older who were screened with colonoscopy at Mount Sinai Medical Center in Miami Beach, Fla., during the last 26 years showed that the majority of cancers (74%) were caught at an early stage when they were treatable by surgery alone, Dr. Heloisa P. Soares said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Treatment with chemotherapy for more advanced colon cancer was also beneficial in this elderly population, whose mean age at diagnosis was 85 years, Dr. Soares said.

In all, 98 patients received chemotherapy as part of their treatment. In patients with stage II colon cancer, chemotherapy resulted in a median overall survival of 75 months, compared with 46 months for patients treated with surgery alone. In stage III colon cancer, chemotherapy likewise improved survival, to 49 months vs. 25 months for surgery alone. However, in stage IV colon cancer, survival was similar: 9 months with and 8 months without chemotherapy.

“More than 70% of newly diagnosed colon cancer cases are in people older than 70 years. Screening in this population pays off, and so does chemotherapy, especially in the early stages,” Dr. Soares said.

In another study presented at the meeting, 161 metastatic colorectal cancer patients aged 80 years or older who were treated with bevacizumab (Avastin) and standard chemotherapy tolerated the regimen as well as their younger counterparts aged 65–79 years, and also had the same progression-free survival. After a median follow-up of 21 months, the median progression-free survival was 10 months for all patients, regardless of their age. The only risk factors for poor outcome were poor performance status (defined as ECOG [Eastern Cooperative Oncology Group] performance status of grade 2 or greater) and a history of arterial thrombotic events.

These results, from the BRITE (Bevacizumab Regimens Investigation of Treatment Effects and Safety) prospective cohort study, show that advanced age in itself should not be considered a deterrent to treating patients, said Dr. Mark Kozloff of Ingalls Memorial Hospital, Harvey, Ill., and the University of Chicago.

BRITE's cohort of elderly metastatic colorectal cancer patients offers the opportunity to analyze bevacizumab and chemotherapy treatment outcomes in a population that is poorly represented in clinical trials, he said in an interview. “These were all comers, unselected patients with metastatic colorectal cancer who are age 65 and older, and just those patients that we encounter most often in our real-world clinical practices. So these data are reassuring.”

Bevacizumab has been shown to prolong overall survival and progression-free survival when added to chemotherapy for metastatic colorectal cancer, but it is associated with an increase in arterial thromboembolic events. Of 1,953 patients in the observational cohort, 896 patients were aged 65–74 years, 533 were aged 75–79 years, and the rest were aged 80 years or older.

There was a lower median overall survival for patients aged 80 years and older (16 months vs. 21 months for patients aged 65–74, and 20 months for patients aged 75–79) but this might be because of less aggressive treatment in this older cohort, he said. Side effects with bevacizumab were similar across all age groups.

Dr. Soares disclosed no conflicts of interest. Dr. Kozloff said he receives research funding from Genentech Inc. which developed Avastin and sponsored BRITE.

'Screening in this population pays off, and so does chemotherapy, especially in the early stages.' DR. SOARES

ORLANDO — Colorectal cancer screening plays an important role in cancer prevention and detection, not just in the “young-old,” but also in the “old-old”–people in their eighties and beyond.

And if a cancer is found, the elderly can also derive considerable benefit from treatments including surgery and chemotherapy, two presenters said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

A retrospective review of 1,390 patients aged 80 years and older who were screened with colonoscopy at Mount Sinai Medical Center in Miami Beach, Fla., during the last 26 years showed that the majority of cancers (74%) were caught at an early stage when they were treatable by surgery alone, Dr. Heloisa P. Soares said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Treatment with chemotherapy for more advanced colon cancer was also beneficial in this elderly population, whose mean age at diagnosis was 85 years, Dr. Soares said.

In all, 98 patients received chemotherapy as part of their treatment. In patients with stage II colon cancer, chemotherapy resulted in a median overall survival of 75 months, compared with 46 months for patients treated with surgery alone. In stage III colon cancer, chemotherapy likewise improved survival, to 49 months vs. 25 months for surgery alone. However, in stage IV colon cancer, survival was similar: 9 months with and 8 months without chemotherapy.

“More than 70% of newly diagnosed colon cancer cases are in people older than 70 years. Screening in this population pays off, and so does chemotherapy, especially in the early stages,” Dr. Soares said.

In another study presented at the meeting, 161 metastatic colorectal cancer patients aged 80 years or older who were treated with bevacizumab (Avastin) and standard chemotherapy tolerated the regimen as well as their younger counterparts aged 65–79 years, and also had the same progression-free survival. After a median follow-up of 21 months, the median progression-free survival was 10 months for all patients, regardless of their age. The only risk factors for poor outcome were poor performance status (defined as ECOG [Eastern Cooperative Oncology Group] performance status of grade 2 or greater) and a history of arterial thrombotic events.

These results, from the BRITE (Bevacizumab Regimens Investigation of Treatment Effects and Safety) prospective cohort study, show that advanced age in itself should not be considered a deterrent to treating patients, said Dr. Mark Kozloff of Ingalls Memorial Hospital, Harvey, Ill., and the University of Chicago.

BRITE's cohort of elderly metastatic colorectal cancer patients offers the opportunity to analyze bevacizumab and chemotherapy treatment outcomes in a population that is poorly represented in clinical trials, he said in an interview. “These were all comers, unselected patients with metastatic colorectal cancer who are age 65 and older, and just those patients that we encounter most often in our real-world clinical practices. So these data are reassuring.”

Bevacizumab has been shown to prolong overall survival and progression-free survival when added to chemotherapy for metastatic colorectal cancer, but it is associated with an increase in arterial thromboembolic events. Of 1,953 patients in the observational cohort, 896 patients were aged 65–74 years, 533 were aged 75–79 years, and the rest were aged 80 years or older.

There was a lower median overall survival for patients aged 80 years and older (16 months vs. 21 months for patients aged 65–74, and 20 months for patients aged 75–79) but this might be because of less aggressive treatment in this older cohort, he said. Side effects with bevacizumab were similar across all age groups.

Dr. Soares disclosed no conflicts of interest. Dr. Kozloff said he receives research funding from Genentech Inc. which developed Avastin and sponsored BRITE.

'Screening in this population pays off, and so does chemotherapy, especially in the early stages.' DR. SOARES

ORLANDO — Liver resection of colorectal metastases was associated with good long-term survival among patients over age 70 years in an analysis based on 20 years of data from an international registry.

Five-year survival after surgery was 37% in a cohort of 729 patients aged 70 years and older and 44% in patients younger than 70 years old. The variations in survival, however, appeared to be associated primarily with the type of disease present rather than solely attributable to patient age, according to lead author Dr. René Adam of Hôpital Paul Brousse, Villejuif, France. Further, 5-year survivals after resection were not different between patients aged 70–75 years, 76–80 years, and 81 years or older.

Perioperative mortality was 4% in the senior group and 2% in the younger group, but selecting candidates for resection based on predictive risk factors would balance some of the risks of surgery, according to Dr. Adam, who presented the data as a poster at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Further, given the slightly higher rate of curative hepatectomy seen in the elderly group, “doing liver resection in these patients is definitely worthwhile,” he said.

He and his colleagues analyzed the LiverMetSurvey registry of patients undergoing surgery for colorectal liver metastases from January 1986 to July 2006. The registry prospectively collected data on 3,662 patients who had resections at 36 centers in 11 countries. Of the 729 patients who were 70 years or older, 463 were 70–75 years; 194 were 75–80 years, and 72 were 80 years or more.

The total cohort of elderly patients was compared with the younger population. A multivariate analysis also was performed to determine which factors were predictive of survival after resection.

Multinodular disease (at least 3 hepatic nodules) was present in 675 (23%) of the younger patients and 80 (11%) of the older patients. Elderly patients had a slightly higher rate of curative hepatectomy, 94% vs. 91% for younger patients. Further, recurrent disease was less common in the elderly patients; 34% of elderly patients and 43% of the younger group had recurrent disease after a mean follow-up of 32 months.

ORLANDO — Liver resection of colorectal metastases was associated with good long-term survival among patients over age 70 years in an analysis based on 20 years of data from an international registry.

Five-year survival after surgery was 37% in a cohort of 729 patients aged 70 years and older and 44% in patients younger than 70 years old. The variations in survival, however, appeared to be associated primarily with the type of disease present rather than solely attributable to patient age, according to lead author Dr. René Adam of Hôpital Paul Brousse, Villejuif, France. Further, 5-year survivals after resection were not different between patients aged 70–75 years, 76–80 years, and 81 years or older.

Perioperative mortality was 4% in the senior group and 2% in the younger group, but selecting candidates for resection based on predictive risk factors would balance some of the risks of surgery, according to Dr. Adam, who presented the data as a poster at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Further, given the slightly higher rate of curative hepatectomy seen in the elderly group, “doing liver resection in these patients is definitely worthwhile,” he said.

He and his colleagues analyzed the LiverMetSurvey registry of patients undergoing surgery for colorectal liver metastases from January 1986 to July 2006. The registry prospectively collected data on 3,662 patients who had resections at 36 centers in 11 countries. Of the 729 patients who were 70 years or older, 463 were 70–75 years; 194 were 75–80 years, and 72 were 80 years or more.

The total cohort of elderly patients was compared with the younger population. A multivariate analysis also was performed to determine which factors were predictive of survival after resection.

Multinodular disease (at least 3 hepatic nodules) was present in 675 (23%) of the younger patients and 80 (11%) of the older patients. Elderly patients had a slightly higher rate of curative hepatectomy, 94% vs. 91% for younger patients. Further, recurrent disease was less common in the elderly patients; 34% of elderly patients and 43% of the younger group had recurrent disease after a mean follow-up of 32 months.

ORLANDO — Liver resection of colorectal metastases was associated with good long-term survival among patients over age 70 years in an analysis based on 20 years of data from an international registry.

Five-year survival after surgery was 37% in a cohort of 729 patients aged 70 years and older and 44% in patients younger than 70 years old. The variations in survival, however, appeared to be associated primarily with the type of disease present rather than solely attributable to patient age, according to lead author Dr. René Adam of Hôpital Paul Brousse, Villejuif, France. Further, 5-year survivals after resection were not different between patients aged 70–75 years, 76–80 years, and 81 years or older.

Perioperative mortality was 4% in the senior group and 2% in the younger group, but selecting candidates for resection based on predictive risk factors would balance some of the risks of surgery, according to Dr. Adam, who presented the data as a poster at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Further, given the slightly higher rate of curative hepatectomy seen in the elderly group, “doing liver resection in these patients is definitely worthwhile,” he said.

He and his colleagues analyzed the LiverMetSurvey registry of patients undergoing surgery for colorectal liver metastases from January 1986 to July 2006. The registry prospectively collected data on 3,662 patients who had resections at 36 centers in 11 countries. Of the 729 patients who were 70 years or older, 463 were 70–75 years; 194 were 75–80 years, and 72 were 80 years or more.

The total cohort of elderly patients was compared with the younger population. A multivariate analysis also was performed to determine which factors were predictive of survival after resection.

Multinodular disease (at least 3 hepatic nodules) was present in 675 (23%) of the younger patients and 80 (11%) of the older patients. Elderly patients had a slightly higher rate of curative hepatectomy, 94% vs. 91% for younger patients. Further, recurrent disease was less common in the elderly patients; 34% of elderly patients and 43% of the younger group had recurrent disease after a mean follow-up of 32 months.

ORLANDO — Most colorectal cancer patients who undergo potentially curative resection of their tumors after age 65 do not receive the follow-up care recommended by clinical practice guidelines, the results of a large population-based study suggest.

Follow-up fell short in 74% of survivors, with the greatest lapse seen in carcinoembryonic antigen (CEA) testing, which is done to detect recurrent colon cancer. Just 30% of survivors had their CEA measured twice a year, Dr. Gregory S. Cooper reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Dr. Cooper of University Hospitals Case Medical Center, Cleveland, mined the linked Surveillance Epidemiology and End Results (SEER)-Medicare database. He and his colleagues analyzed 9,246 patients older than 65 years with local or regional colorectal cancer that was diagnosed in 2000 and 2001 and resected with curative intent. The mean age of the patients was 77 years; 55% were female, 87% were white.

Medicare claims identified procedures performed between 6 and 42 months after diagnosis. These included office visits, colonoscopy, CT or PET scans, and CEA testing. Patients were deemed to have been treated according to American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines if they had at least two office visits per year, at least two CEA tests per year, at least one colonoscopy within 3 years of their resection, and a yearly CT scan for any poorly differentiated cancer.

Dr. Cooper found just 30% of patients had the requisite testing for CEA; 74% had a colonoscopy within 3 years and 90% had office visits according to the recommended schedule. The study was supported by the American Cancer Society. Dr. Cooper had no conflicts of interest to disclose.

ORLANDO — Most colorectal cancer patients who undergo potentially curative resection of their tumors after age 65 do not receive the follow-up care recommended by clinical practice guidelines, the results of a large population-based study suggest.

Follow-up fell short in 74% of survivors, with the greatest lapse seen in carcinoembryonic antigen (CEA) testing, which is done to detect recurrent colon cancer. Just 30% of survivors had their CEA measured twice a year, Dr. Gregory S. Cooper reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Dr. Cooper of University Hospitals Case Medical Center, Cleveland, mined the linked Surveillance Epidemiology and End Results (SEER)-Medicare database. He and his colleagues analyzed 9,246 patients older than 65 years with local or regional colorectal cancer that was diagnosed in 2000 and 2001 and resected with curative intent. The mean age of the patients was 77 years; 55% were female, 87% were white.

Medicare claims identified procedures performed between 6 and 42 months after diagnosis. These included office visits, colonoscopy, CT or PET scans, and CEA testing. Patients were deemed to have been treated according to American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines if they had at least two office visits per year, at least two CEA tests per year, at least one colonoscopy within 3 years of their resection, and a yearly CT scan for any poorly differentiated cancer.

Dr. Cooper found just 30% of patients had the requisite testing for CEA; 74% had a colonoscopy within 3 years and 90% had office visits according to the recommended schedule. The study was supported by the American Cancer Society. Dr. Cooper had no conflicts of interest to disclose.

ORLANDO — Most colorectal cancer patients who undergo potentially curative resection of their tumors after age 65 do not receive the follow-up care recommended by clinical practice guidelines, the results of a large population-based study suggest.

Follow-up fell short in 74% of survivors, with the greatest lapse seen in carcinoembryonic antigen (CEA) testing, which is done to detect recurrent colon cancer. Just 30% of survivors had their CEA measured twice a year, Dr. Gregory S. Cooper reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

Dr. Cooper of University Hospitals Case Medical Center, Cleveland, mined the linked Surveillance Epidemiology and End Results (SEER)-Medicare database. He and his colleagues analyzed 9,246 patients older than 65 years with local or regional colorectal cancer that was diagnosed in 2000 and 2001 and resected with curative intent. The mean age of the patients was 77 years; 55% were female, 87% were white.

Medicare claims identified procedures performed between 6 and 42 months after diagnosis. These included office visits, colonoscopy, CT or PET scans, and CEA testing. Patients were deemed to have been treated according to American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines if they had at least two office visits per year, at least two CEA tests per year, at least one colonoscopy within 3 years of their resection, and a yearly CT scan for any poorly differentiated cancer.

Dr. Cooper found just 30% of patients had the requisite testing for CEA; 74% had a colonoscopy within 3 years and 90% had office visits according to the recommended schedule. The study was supported by the American Cancer Society. Dr. Cooper had no conflicts of interest to disclose.

ATLANTA — Elevated C-peptide and hemoglobin A_1c levels were associated with low levels of prostate-specific antigen in obese, nondiabetic black and white men in a cross-sectional study.

PSA levels were approximately 50% lower among black men with higher levels of C-peptide, a biomarker of insulin, whereas among white men, PSA levels were lower with increasing levels of HbA_1c, a marker of blood glucose control, said Jay H. Fowke, Ph.D., at a conference sponsored by the American Association for Cancer Research.

Such metabolic disturbances may mask the presence of prostate cancer and delay a diagnosis until the cancer is too advanced for successful treatment, said Dr. Fowke of Vanderbilt University, Nashville, Tenn.

A number of studies have looked at obesity and PSA levels, and some findings have suggested that obese men have lower PSA levels. Black men are more likely than white men to be diagnosed with advanced prostate cancer and have a poorer prognosis following treatment.

Dr. Fowke and his Vanderbilt colleagues looked at the biomarkers associated with obesity to see if there was a link between them and lower PSA levels.

They selected at random 121 black men and a similar number of white men who were participants in the Southern Community Cohort Study, a National Cancer Institute-funded initiative that monitors the health of 90,000 men and women between the ages of 40 and 79 years throughout the southern United States.

The proportion of obese and overweight men was the same in each group, and none of the men had a prior diagnosis of prostate cancer or diabetes.

Blood samples from each participant were analyzed for C-peptide and HbA_1c, as well as leptin and adiponectin.

There were “subtle” differences between black and white men, Dr. Fowke said.

PSA levels did not significantly differ across leptin or adiponectin levels, but were 50% lower among black men with higher C-peptide levels. This association was especially prevalent among obese black men, he noted.

In contrast, C-peptide was not associated with PSA level among white men. In this group, PSA levels were 50% lower in men with higher levels of HbA_1c.

The association between HbA_1c and PSA seemed to be stronger among white men with a body mass index of less than 30 kg/m

The finding suggests that there may be differences between white and black men in the way PSA responds to obesity.

In an interview, Dr. Fowke said these are basic research findings that do not indicate a need to change current screening recommendations. However, the findings do suggest that clinicians who manage obese and overweight patients should be aware that PSA level may not be as sensitive for the detection of prostate cancer in these patients.

“They may want to put more emphasis on a digital rectal exam, for example. Or they might want to follow these patients more carefully and do PSA velocity testing to see if there is a large change in PSA values over time.”

Dr. Fowke said he had no conflicts of interest to declare. The study was sponsored by the National Cancer Institute.

Physicians might want to do PSA velocity testing to see if there is a large change in PSA values over time. DR. FOWKE

ATLANTA — Elevated C-peptide and hemoglobin A_1c levels were associated with low levels of prostate-specific antigen in obese, nondiabetic black and white men in a cross-sectional study.

PSA levels were approximately 50% lower among black men with higher levels of C-peptide, a biomarker of insulin, whereas among white men, PSA levels were lower with increasing levels of HbA_1c, a marker of blood glucose control, said Jay H. Fowke, Ph.D., at a conference sponsored by the American Association for Cancer Research.

Such metabolic disturbances may mask the presence of prostate cancer and delay a diagnosis until the cancer is too advanced for successful treatment, said Dr. Fowke of Vanderbilt University, Nashville, Tenn.

A number of studies have looked at obesity and PSA levels, and some findings have suggested that obese men have lower PSA levels. Black men are more likely than white men to be diagnosed with advanced prostate cancer and have a poorer prognosis following treatment.

Dr. Fowke and his Vanderbilt colleagues looked at the biomarkers associated with obesity to see if there was a link between them and lower PSA levels.

They selected at random 121 black men and a similar number of white men who were participants in the Southern Community Cohort Study, a National Cancer Institute-funded initiative that monitors the health of 90,000 men and women between the ages of 40 and 79 years throughout the southern United States.

The proportion of obese and overweight men was the same in each group, and none of the men had a prior diagnosis of prostate cancer or diabetes.

Blood samples from each participant were analyzed for C-peptide and HbA_1c, as well as leptin and adiponectin.

There were “subtle” differences between black and white men, Dr. Fowke said.

PSA levels did not significantly differ across leptin or adiponectin levels, but were 50% lower among black men with higher C-peptide levels. This association was especially prevalent among obese black men, he noted.

In contrast, C-peptide was not associated with PSA level among white men. In this group, PSA levels were 50% lower in men with higher levels of HbA_1c.

The association between HbA_1c and PSA seemed to be stronger among white men with a body mass index of less than 30 kg/m

The finding suggests that there may be differences between white and black men in the way PSA responds to obesity.

In an interview, Dr. Fowke said these are basic research findings that do not indicate a need to change current screening recommendations. However, the findings do suggest that clinicians who manage obese and overweight patients should be aware that PSA level may not be as sensitive for the detection of prostate cancer in these patients.

“They may want to put more emphasis on a digital rectal exam, for example. Or they might want to follow these patients more carefully and do PSA velocity testing to see if there is a large change in PSA values over time.”

Dr. Fowke said he had no conflicts of interest to declare. The study was sponsored by the National Cancer Institute.

Physicians might want to do PSA velocity testing to see if there is a large change in PSA values over time. DR. FOWKE

ATLANTA — Elevated C-peptide and hemoglobin A_1c levels were associated with low levels of prostate-specific antigen in obese, nondiabetic black and white men in a cross-sectional study.

PSA levels were approximately 50% lower among black men with higher levels of C-peptide, a biomarker of insulin, whereas among white men, PSA levels were lower with increasing levels of HbA_1c, a marker of blood glucose control, said Jay H. Fowke, Ph.D., at a conference sponsored by the American Association for Cancer Research.

Such metabolic disturbances may mask the presence of prostate cancer and delay a diagnosis until the cancer is too advanced for successful treatment, said Dr. Fowke of Vanderbilt University, Nashville, Tenn.

A number of studies have looked at obesity and PSA levels, and some findings have suggested that obese men have lower PSA levels. Black men are more likely than white men to be diagnosed with advanced prostate cancer and have a poorer prognosis following treatment.

Dr. Fowke and his Vanderbilt colleagues looked at the biomarkers associated with obesity to see if there was a link between them and lower PSA levels.

They selected at random 121 black men and a similar number of white men who were participants in the Southern Community Cohort Study, a National Cancer Institute-funded initiative that monitors the health of 90,000 men and women between the ages of 40 and 79 years throughout the southern United States.

The proportion of obese and overweight men was the same in each group, and none of the men had a prior diagnosis of prostate cancer or diabetes.

Blood samples from each participant were analyzed for C-peptide and HbA_1c, as well as leptin and adiponectin.

There were “subtle” differences between black and white men, Dr. Fowke said.

PSA levels did not significantly differ across leptin or adiponectin levels, but were 50% lower among black men with higher C-peptide levels. This association was especially prevalent among obese black men, he noted.

In contrast, C-peptide was not associated with PSA level among white men. In this group, PSA levels were 50% lower in men with higher levels of HbA_1c.

The association between HbA_1c and PSA seemed to be stronger among white men with a body mass index of less than 30 kg/m

The finding suggests that there may be differences between white and black men in the way PSA responds to obesity.

In an interview, Dr. Fowke said these are basic research findings that do not indicate a need to change current screening recommendations. However, the findings do suggest that clinicians who manage obese and overweight patients should be aware that PSA level may not be as sensitive for the detection of prostate cancer in these patients.

“They may want to put more emphasis on a digital rectal exam, for example. Or they might want to follow these patients more carefully and do PSA velocity testing to see if there is a large change in PSA values over time.”

Dr. Fowke said he had no conflicts of interest to declare. The study was sponsored by the National Cancer Institute.

Physicians might want to do PSA velocity testing to see if there is a large change in PSA values over time. DR. FOWKE

An extract derived from the roots of the rhubarb plant has been shown in a randomized, placebo-controlled trial to provide relief of vasomotor symptoms in peri- and postmenopausal women, Dr. David S. Riley told the annual meeting of the North American Menopause Society.

The trial, which was conducted at University Hospital, Frankfurt, Germany, showed that women who consumed one tablet containing 4 mg of the extract Rheum rhaponticum, or ERr 731, daily for 12 weeks had a significant reduction in the number and severity of hot flashes, compared with women on placebo.

Although ERr 731 has been available in Germany for several years, it is still relatively unknown on this side of the Atlantic, Dr. Riley of the University of New Mexico, Albuquerque, explained in a telephone interview. As a consultant to the German researchers, he thought it would be interesting to present their data to clinicians in the United States.

“This is a substance that has been on the market in Germany since 1993, and the research was done to reregister it as an herbal medication,” said Dr. Riley, who also is editor in chief of Explore, The Journal of Science and Healing.

Hormone therapy, the standard for relieving vasomotor symptoms of menopause, can have unwanted side effects; other therapies, which do not have troublesome side effects, are of questionable efficacy, he said.

In this study, 112 perimenopausal women were randomized to 4 mg/day of ERr 731 or to placebo for 12 weeks. At the beginning of the trial, all of the women had a menopause rating scale (MRS) score of at least 18, which meant that their menopausal symptoms were moderate to severe. Factors rated in the MRS score included hot flashes and sweating, heart complaints, sleep disturbances, depressive mood, irritability, anxiety, physical and mental exhaustion, sexual problems, urinary tract complaints, vaginal dryness, and joint and muscle complaints.

The women rated their symptoms on a scale from 0 (no symptoms) to 4 (very severe symptoms). The maximum obtainable MRS score was 44 points.

After 12 weeks of treatment, there was a significant reduction in MRS score in the women taking the extract; 46 of the 56 (82%) women randomized to ERr 731 had a decrease of at least 10 points in their MRS score, compared with 2 (4%) of the women randomized to placebo.

ERr 731 was associated with a significant reduction in hot flashes, compared with placebo, from 11 a day at baseline, to 4 a day at 12 weeks, Dr. Riley said.

The compound was safe and was associated with no breast tenderness or increase in endometrial thickness as assessed on ultrasound and biopsies, no changes in liver enzymes, no changes in blood pressure, no changes in weight, no increase in estradiol or progesterone, and no enhanced bone turnover. “Women are looking for safe and natural alternatives to hormones to relieve their menopausal symptoms. … This compound is exciting and shows promise.”

An extract derived from the roots of the rhubarb plant has been shown in a randomized, placebo-controlled trial to provide relief of vasomotor symptoms in peri- and postmenopausal women, Dr. David S. Riley told the annual meeting of the North American Menopause Society.

The trial, which was conducted at University Hospital, Frankfurt, Germany, showed that women who consumed one tablet containing 4 mg of the extract Rheum rhaponticum, or ERr 731, daily for 12 weeks had a significant reduction in the number and severity of hot flashes, compared with women on placebo.

Although ERr 731 has been available in Germany for several years, it is still relatively unknown on this side of the Atlantic, Dr. Riley of the University of New Mexico, Albuquerque, explained in a telephone interview. As a consultant to the German researchers, he thought it would be interesting to present their data to clinicians in the United States.

“This is a substance that has been on the market in Germany since 1993, and the research was done to reregister it as an herbal medication,” said Dr. Riley, who also is editor in chief of Explore, The Journal of Science and Healing.

Hormone therapy, the standard for relieving vasomotor symptoms of menopause, can have unwanted side effects; other therapies, which do not have troublesome side effects, are of questionable efficacy, he said.

In this study, 112 perimenopausal women were randomized to 4 mg/day of ERr 731 or to placebo for 12 weeks. At the beginning of the trial, all of the women had a menopause rating scale (MRS) score of at least 18, which meant that their menopausal symptoms were moderate to severe. Factors rated in the MRS score included hot flashes and sweating, heart complaints, sleep disturbances, depressive mood, irritability, anxiety, physical and mental exhaustion, sexual problems, urinary tract complaints, vaginal dryness, and joint and muscle complaints.

The women rated their symptoms on a scale from 0 (no symptoms) to 4 (very severe symptoms). The maximum obtainable MRS score was 44 points.

After 12 weeks of treatment, there was a significant reduction in MRS score in the women taking the extract; 46 of the 56 (82%) women randomized to ERr 731 had a decrease of at least 10 points in their MRS score, compared with 2 (4%) of the women randomized to placebo.

ERr 731 was associated with a significant reduction in hot flashes, compared with placebo, from 11 a day at baseline, to 4 a day at 12 weeks, Dr. Riley said.

The compound was safe and was associated with no breast tenderness or increase in endometrial thickness as assessed on ultrasound and biopsies, no changes in liver enzymes, no changes in blood pressure, no changes in weight, no increase in estradiol or progesterone, and no enhanced bone turnover. “Women are looking for safe and natural alternatives to hormones to relieve their menopausal symptoms. … This compound is exciting and shows promise.”

An extract derived from the roots of the rhubarb plant has been shown in a randomized, placebo-controlled trial to provide relief of vasomotor symptoms in peri- and postmenopausal women, Dr. David S. Riley told the annual meeting of the North American Menopause Society.

The trial, which was conducted at University Hospital, Frankfurt, Germany, showed that women who consumed one tablet containing 4 mg of the extract Rheum rhaponticum, or ERr 731, daily for 12 weeks had a significant reduction in the number and severity of hot flashes, compared with women on placebo.

Although ERr 731 has been available in Germany for several years, it is still relatively unknown on this side of the Atlantic, Dr. Riley of the University of New Mexico, Albuquerque, explained in a telephone interview. As a consultant to the German researchers, he thought it would be interesting to present their data to clinicians in the United States.

“This is a substance that has been on the market in Germany since 1993, and the research was done to reregister it as an herbal medication,” said Dr. Riley, who also is editor in chief of Explore, The Journal of Science and Healing.

Hormone therapy, the standard for relieving vasomotor symptoms of menopause, can have unwanted side effects; other therapies, which do not have troublesome side effects, are of questionable efficacy, he said.

In this study, 112 perimenopausal women were randomized to 4 mg/day of ERr 731 or to placebo for 12 weeks. At the beginning of the trial, all of the women had a menopause rating scale (MRS) score of at least 18, which meant that their menopausal symptoms were moderate to severe. Factors rated in the MRS score included hot flashes and sweating, heart complaints, sleep disturbances, depressive mood, irritability, anxiety, physical and mental exhaustion, sexual problems, urinary tract complaints, vaginal dryness, and joint and muscle complaints.

The women rated their symptoms on a scale from 0 (no symptoms) to 4 (very severe symptoms). The maximum obtainable MRS score was 44 points.

After 12 weeks of treatment, there was a significant reduction in MRS score in the women taking the extract; 46 of the 56 (82%) women randomized to ERr 731 had a decrease of at least 10 points in their MRS score, compared with 2 (4%) of the women randomized to placebo.

ERr 731 was associated with a significant reduction in hot flashes, compared with placebo, from 11 a day at baseline, to 4 a day at 12 weeks, Dr. Riley said.

The compound was safe and was associated with no breast tenderness or increase in endometrial thickness as assessed on ultrasound and biopsies, no changes in liver enzymes, no changes in blood pressure, no changes in weight, no increase in estradiol or progesterone, and no enhanced bone turnover. “Women are looking for safe and natural alternatives to hormones to relieve their menopausal symptoms. … This compound is exciting and shows promise.”

Treatment with desvenlafaxine succinate, an experimental nonhormonal therapy, continues to reduce the frequency and severity of moderate to severe hot flashes out to 26 weeks.

The drug, a selective serotonin norepinephrine reuptake inhibitor (SNRI), has been shown to be effective in relieving this menopausal symptom in a 12-week trial reported last year.

The current findings, from an extension of that trial, show that desvenlafaxine continues to be effective for more than 6 months, said Dr. Risa Kagan, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, and a consultant for Wyeth, which developed the drug.

“This is good news for [those] bothered [by hot flashes] and who are looking for alternatives to estrogen or hormone replacement therapy,” she said in an interview.

In the continuation of the multicenter, randomized, double-blind, placebo-controlled trial, 541 women who had at least 50 moderate to severe hot flashes a week and who received 150 mg/day of desvenlafaxine maintained the significant reduction in the number of hot flashes they had achieved by week 12 of the trial (from 10 a day to 2 a day) during the 26-week study, she said at the annual meeting of the North American Menopause Society.

The improvement in hot flash frequency and severity was dose dependent. The 118 women who were randomized to desvenlafaxine 100 mg/day had a less robust decrease in hot flash frequency, and went from an average of 10 to 4 hot flashes a day by week 26. The 138 women who were randomized to placebo also saw a reduction in their hot flashes from baseline, from an average of 10 to 6 a day.

The women recorded their hot flash episodes in diaries and were assessed weekly for the first 12 months, and then every 3 weeks thereafter.

The reductions from baseline in the frequency of moderate to severe hot flashes “were significantly greater, compared with placebo, at all time points with desvenlafaxine 150 mg and at most time points with desvenlafaxine 100 mg throughout the 26 weeks of the study,” Dr. Kagan said.

The most common adverse event was nausea, which improved with time. “Nausea is not unique to this agent, and is something that is associated with many of this category of drugs. But it was responsible for about 12.7% of the desvenlafaxine subjects' withdrawing from the study,” she said.

Fluctuations and the eventual decline in estrogen levels in menopause may alter brain serotonin and norepinephrine transmitter levels, which may in turn produce instability in thermoregulatory function and, as a result, hot flashes, Dr. Kagan said. “[We] hope drugs like desvenlafaxine, which act on these transmitters, may provide nonhormonal relief of menopausal vasomotor symptoms.”

Treatment with desvenlafaxine succinate, an experimental nonhormonal therapy, continues to reduce the frequency and severity of moderate to severe hot flashes out to 26 weeks.

The drug, a selective serotonin norepinephrine reuptake inhibitor (SNRI), has been shown to be effective in relieving this menopausal symptom in a 12-week trial reported last year.

The current findings, from an extension of that trial, show that desvenlafaxine continues to be effective for more than 6 months, said Dr. Risa Kagan, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, and a consultant for Wyeth, which developed the drug.

“This is good news for [those] bothered [by hot flashes] and who are looking for alternatives to estrogen or hormone replacement therapy,” she said in an interview.

In the continuation of the multicenter, randomized, double-blind, placebo-controlled trial, 541 women who had at least 50 moderate to severe hot flashes a week and who received 150 mg/day of desvenlafaxine maintained the significant reduction in the number of hot flashes they had achieved by week 12 of the trial (from 10 a day to 2 a day) during the 26-week study, she said at the annual meeting of the North American Menopause Society.

The improvement in hot flash frequency and severity was dose dependent. The 118 women who were randomized to desvenlafaxine 100 mg/day had a less robust decrease in hot flash frequency, and went from an average of 10 to 4 hot flashes a day by week 26. The 138 women who were randomized to placebo also saw a reduction in their hot flashes from baseline, from an average of 10 to 6 a day.

The women recorded their hot flash episodes in diaries and were assessed weekly for the first 12 months, and then every 3 weeks thereafter.

The reductions from baseline in the frequency of moderate to severe hot flashes “were significantly greater, compared with placebo, at all time points with desvenlafaxine 150 mg and at most time points with desvenlafaxine 100 mg throughout the 26 weeks of the study,” Dr. Kagan said.

The most common adverse event was nausea, which improved with time. “Nausea is not unique to this agent, and is something that is associated with many of this category of drugs. But it was responsible for about 12.7% of the desvenlafaxine subjects' withdrawing from the study,” she said.

Fluctuations and the eventual decline in estrogen levels in menopause may alter brain serotonin and norepinephrine transmitter levels, which may in turn produce instability in thermoregulatory function and, as a result, hot flashes, Dr. Kagan said. “[We] hope drugs like desvenlafaxine, which act on these transmitters, may provide nonhormonal relief of menopausal vasomotor symptoms.”

Treatment with desvenlafaxine succinate, an experimental nonhormonal therapy, continues to reduce the frequency and severity of moderate to severe hot flashes out to 26 weeks.

The drug, a selective serotonin norepinephrine reuptake inhibitor (SNRI), has been shown to be effective in relieving this menopausal symptom in a 12-week trial reported last year.

The current findings, from an extension of that trial, show that desvenlafaxine continues to be effective for more than 6 months, said Dr. Risa Kagan, professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, and a consultant for Wyeth, which developed the drug.

“This is good news for [those] bothered [by hot flashes] and who are looking for alternatives to estrogen or hormone replacement therapy,” she said in an interview.

In the continuation of the multicenter, randomized, double-blind, placebo-controlled trial, 541 women who had at least 50 moderate to severe hot flashes a week and who received 150 mg/day of desvenlafaxine maintained the significant reduction in the number of hot flashes they had achieved by week 12 of the trial (from 10 a day to 2 a day) during the 26-week study, she said at the annual meeting of the North American Menopause Society.

The improvement in hot flash frequency and severity was dose dependent. The 118 women who were randomized to desvenlafaxine 100 mg/day had a less robust decrease in hot flash frequency, and went from an average of 10 to 4 hot flashes a day by week 26. The 138 women who were randomized to placebo also saw a reduction in their hot flashes from baseline, from an average of 10 to 6 a day.

The women recorded their hot flash episodes in diaries and were assessed weekly for the first 12 months, and then every 3 weeks thereafter.

The reductions from baseline in the frequency of moderate to severe hot flashes “were significantly greater, compared with placebo, at all time points with desvenlafaxine 150 mg and at most time points with desvenlafaxine 100 mg throughout the 26 weeks of the study,” Dr. Kagan said.

The most common adverse event was nausea, which improved with time. “Nausea is not unique to this agent, and is something that is associated with many of this category of drugs. But it was responsible for about 12.7% of the desvenlafaxine subjects' withdrawing from the study,” she said.

Fluctuations and the eventual decline in estrogen levels in menopause may alter brain serotonin and norepinephrine transmitter levels, which may in turn produce instability in thermoregulatory function and, as a result, hot flashes, Dr. Kagan said. “[We] hope drugs like desvenlafaxine, which act on these transmitters, may provide nonhormonal relief of menopausal vasomotor symptoms.”

ATLANTA — Women who opt for hormone therapy to ease their discomfort from hot flashes and other menopausal symptoms often do so without knowing their risk of developing adverse effects.

Now, data from the Women's Health Initiative trials of hormone therapy (HT) may help women make more informed decisions about their risk for venous thromboembolism, should they choose to resume or start hormones.

A nested case-control study from the WHI presented at the annual meeting of the American Society of Hematology has found that excessively high levels of the coagulation factor D-dimer, in the presence of HT, significantly increases a woman's risk of developing venous thrombosis.

“If your D-dimer was in the top quarter of population distribution and you were assigned to HT, your relative risk of deep vein thrombosis was increased sixfold, compared to women whose D-dimer was low and who were assigned placebo,” principal investigator Dr. Mary Cushman, professor of medicine at the University of Vermont, Burlington, said.

Dr. Cushman and her colleagues measured baseline levels of potential coagulation risk factors to see if they could pinpoint women at higher risk of venous thrombosis with hormones. They did a nested case-control study that measured baseline levels of these factors in 215 participants of the WHI who developed venous thrombosis, and 867 age-matched controls.

The women were all participants of two placebo-controlled double-blind randomized WHI trials evaluating the following regimens: conjugated equine estrogens alone, or estrogen plus medroxyprogesterone acetate. The mean age of the women in the analysis was 66 and ranged from 50 to 79 years.

Women who had low levels of protein C, free protein S, and antithrombin, and who had high levels of D-dimer, prostatic acid phosphatase, and prothrombin fragment 1–2 had an elevated risk of venous thrombo-embolism. The highest risk was associated with women who had D-dimer in the top quartile and who were taking hormone therapy.

In an interview, Dr. Cushman cautioned that testing for D-dimer is not yet ready for prime time because there are currently no standardized tests specifically designed to gauge venous thrombosis risk.

“There are various D-dimer assays commercially available, but choosing a proper threshold and so forth among all the different commercially available assays is a challenge,” she said. “We used a particular assay in our analysis, and studies would be needed assessing other assays before using this in clinical practice.”

The take home is about the additive nature of these coagulation factor abnormalities. The potential for clinical applicability is potentially there.”

If your D-dimer was in the top quarter, your relative risk of DVT was increased sixfold. DR. CUSHMAN

ATLANTA — Women who opt for hormone therapy to ease their discomfort from hot flashes and other menopausal symptoms often do so without knowing their risk of developing adverse effects.

Now, data from the Women's Health Initiative trials of hormone therapy (HT) may help women make more informed decisions about their risk for venous thromboembolism, should they choose to resume or start hormones.

A nested case-control study from the WHI presented at the annual meeting of the American Society of Hematology has found that excessively high levels of the coagulation factor D-dimer, in the presence of HT, significantly increases a woman's risk of developing venous thrombosis.

“If your D-dimer was in the top quarter of population distribution and you were assigned to HT, your relative risk of deep vein thrombosis was increased sixfold, compared to women whose D-dimer was low and who were assigned placebo,” principal investigator Dr. Mary Cushman, professor of medicine at the University of Vermont, Burlington, said.

Dr. Cushman and her colleagues measured baseline levels of potential coagulation risk factors to see if they could pinpoint women at higher risk of venous thrombosis with hormones. They did a nested case-control study that measured baseline levels of these factors in 215 participants of the WHI who developed venous thrombosis, and 867 age-matched controls.

The women were all participants of two placebo-controlled double-blind randomized WHI trials evaluating the following regimens: conjugated equine estrogens alone, or estrogen plus medroxyprogesterone acetate. The mean age of the women in the analysis was 66 and ranged from 50 to 79 years.

Women who had low levels of protein C, free protein S, and antithrombin, and who had high levels of D-dimer, prostatic acid phosphatase, and prothrombin fragment 1–2 had an elevated risk of venous thrombo-embolism. The highest risk was associated with women who had D-dimer in the top quartile and who were taking hormone therapy.

In an interview, Dr. Cushman cautioned that testing for D-dimer is not yet ready for prime time because there are currently no standardized tests specifically designed to gauge venous thrombosis risk.

“There are various D-dimer assays commercially available, but choosing a proper threshold and so forth among all the different commercially available assays is a challenge,” she said. “We used a particular assay in our analysis, and studies would be needed assessing other assays before using this in clinical practice.”

The take home is about the additive nature of these coagulation factor abnormalities. The potential for clinical applicability is potentially there.”

If your D-dimer was in the top quarter, your relative risk of DVT was increased sixfold. DR. CUSHMAN

ATLANTA — Women who opt for hormone therapy to ease their discomfort from hot flashes and other menopausal symptoms often do so without knowing their risk of developing adverse effects.

Now, data from the Women's Health Initiative trials of hormone therapy (HT) may help women make more informed decisions about their risk for venous thromboembolism, should they choose to resume or start hormones.

A nested case-control study from the WHI presented at the annual meeting of the American Society of Hematology has found that excessively high levels of the coagulation factor D-dimer, in the presence of HT, significantly increases a woman's risk of developing venous thrombosis.

“If your D-dimer was in the top quarter of population distribution and you were assigned to HT, your relative risk of deep vein thrombosis was increased sixfold, compared to women whose D-dimer was low and who were assigned placebo,” principal investigator Dr. Mary Cushman, professor of medicine at the University of Vermont, Burlington, said.

Dr. Cushman and her colleagues measured baseline levels of potential coagulation risk factors to see if they could pinpoint women at higher risk of venous thrombosis with hormones. They did a nested case-control study that measured baseline levels of these factors in 215 participants of the WHI who developed venous thrombosis, and 867 age-matched controls.

The women were all participants of two placebo-controlled double-blind randomized WHI trials evaluating the following regimens: conjugated equine estrogens alone, or estrogen plus medroxyprogesterone acetate. The mean age of the women in the analysis was 66 and ranged from 50 to 79 years.

Women who had low levels of protein C, free protein S, and antithrombin, and who had high levels of D-dimer, prostatic acid phosphatase, and prothrombin fragment 1–2 had an elevated risk of venous thrombo-embolism. The highest risk was associated with women who had D-dimer in the top quartile and who were taking hormone therapy.

In an interview, Dr. Cushman cautioned that testing for D-dimer is not yet ready for prime time because there are currently no standardized tests specifically designed to gauge venous thrombosis risk.

“There are various D-dimer assays commercially available, but choosing a proper threshold and so forth among all the different commercially available assays is a challenge,” she said. “We used a particular assay in our analysis, and studies would be needed assessing other assays before using this in clinical practice.”

The take home is about the additive nature of these coagulation factor abnormalities. The potential for clinical applicability is potentially there.”

If your D-dimer was in the top quarter, your relative risk of DVT was increased sixfold. DR. CUSHMAN

ATLANTA — Vitamin D deficiency was strongly associated with high cardiac iron and increased ventricular dysfunction in a retrospective review of 24 young thal-assemia major patients.

A review of their medical records showed levels of vitamin D(25[OH]D), the predominant circulating form of vitamin D, were “markedly depressed” in 13 patients and borderline depressed in the remaining patients, said Dr. John C. Wood of Children's Hospital Los Angeles and Keck School of Medicine at the University of Southern California, Los Angeles. There were 11 girls and 13 boys; mean age was 15 years.

Vitamin D(25[OH]D) levels less than 20 ng/mL are considered deficient and D(25[OH]D) levels 20–30 ng/mL are borderline or insufficient, Dr. Wood said in a presentation at the annual meeting of the American Society of Hematology. In this study, the mean D(25[OH]D) was 17 ng/mL.

The vitamin D levels were then compared with cardiac R2*–a surrogate MRI measure of the amount of iron in the heart—and left ventricular ejection fraction (LVEF) from each patient's most recent cardiac MRI. As vitamin D levels decreased, cardiac R2* increased. Vitamin D(25[OH]D) levels below 13 ng/mL were associated with severe cardiac iron loading. LVEF also decreased as D25-OH decreased.

“In our MRI laboratory, an ejection fraction less than 56% is considered abnormal and indicates poor pump function. In these patients, there was a proportional association between vitamin D(25[OH]D) levels and cardiac function. The four patients with the lowest D(25[OH]D) had an LVEF between 50% and 54%,” he said.

The population also was moderately iron overloaded, with mean ferritin levels of 2,089 ng/mL, liver iron 14 mg/g dry weight, transferrin saturation 84%, and cardiac R2* 65 Hz. The normal R2* should not exceed 50 Hz. “Vitamin D deficiency … is extremely common in thalassemia. Twenty-three of the 24 patients in our study had levels that are considered inadequate to ensure optimal calcium absorption and bone mineralization,” he said in an interview. Low vitamin D is linked to decreased cardiac function, muscle weakness, glucose insensitivity, and refractory congestive heart failure.

Increased iron in the heart becomes evident in children with thalassemia major around the age of 9 years. Two-thirds of adults with thalassemia have cardiac iron deposition. Iron cardiomyopathy is the leading cause of death in thalassemia. “Our study describes an association between low vitamin D, high cardiac iron, and increased ventricular dysfunction. We cannot prove [cause and effect], but vitamin D might be worsening the cardiac iron overload and the cardiac dysfunction through its modulation of calcium signaling in these patients.”

“Vitamin D deficiency is extremely common in thalassemia, and since osteoporosis is ubiquitous in this disease, vitamin D screening and replacement are probably indicated regardless of the heart findings,” Dr. Wood said.

He added that low vitamin D produces secondary hyperparathyroidism, which exacerbates heart failure of any etiology. Because of this, thalassemia patients with ventricular dysfunction should have their vitamin D levels assessed, and replacement should be started if these levels are low.

The National Heart, Lung, and Blood Institute, the Centers for Disease Control and Prevention, and Novartis Pharma funded the study. Dr. Wood disclosed he receives research funding and honoraria from Novartis and Apotex, and is a consultant to Novartis.

Vitamin D might be worsening the cardiac iron overload and dysfunction by modulating calcium signaling. DR. WOOD

ATLANTA — Vitamin D deficiency was strongly associated with high cardiac iron and increased ventricular dysfunction in a retrospective review of 24 young thal-assemia major patients.

A review of their medical records showed levels of vitamin D(25[OH]D), the predominant circulating form of vitamin D, were “markedly depressed” in 13 patients and borderline depressed in the remaining patients, said Dr. John C. Wood of Children's Hospital Los Angeles and Keck School of Medicine at the University of Southern California, Los Angeles. There were 11 girls and 13 boys; mean age was 15 years.

Vitamin D(25[OH]D) levels less than 20 ng/mL are considered deficient and D(25[OH]D) levels 20–30 ng/mL are borderline or insufficient, Dr. Wood said in a presentation at the annual meeting of the American Society of Hematology. In this study, the mean D(25[OH]D) was 17 ng/mL.

The vitamin D levels were then compared with cardiac R2*–a surrogate MRI measure of the amount of iron in the heart—and left ventricular ejection fraction (LVEF) from each patient's most recent cardiac MRI. As vitamin D levels decreased, cardiac R2* increased. Vitamin D(25[OH]D) levels below 13 ng/mL were associated with severe cardiac iron loading. LVEF also decreased as D25-OH decreased.

“In our MRI laboratory, an ejection fraction less than 56% is considered abnormal and indicates poor pump function. In these patients, there was a proportional association between vitamin D(25[OH]D) levels and cardiac function. The four patients with the lowest D(25[OH]D) had an LVEF between 50% and 54%,” he said.

The population also was moderately iron overloaded, with mean ferritin levels of 2,089 ng/mL, liver iron 14 mg/g dry weight, transferrin saturation 84%, and cardiac R2* 65 Hz. The normal R2* should not exceed 50 Hz. “Vitamin D deficiency … is extremely common in thalassemia. Twenty-three of the 24 patients in our study had levels that are considered inadequate to ensure optimal calcium absorption and bone mineralization,” he said in an interview. Low vitamin D is linked to decreased cardiac function, muscle weakness, glucose insensitivity, and refractory congestive heart failure.

Increased iron in the heart becomes evident in children with thalassemia major around the age of 9 years. Two-thirds of adults with thalassemia have cardiac iron deposition. Iron cardiomyopathy is the leading cause of death in thalassemia. “Our study describes an association between low vitamin D, high cardiac iron, and increased ventricular dysfunction. We cannot prove [cause and effect], but vitamin D might be worsening the cardiac iron overload and the cardiac dysfunction through its modulation of calcium signaling in these patients.”

“Vitamin D deficiency is extremely common in thalassemia, and since osteoporosis is ubiquitous in this disease, vitamin D screening and replacement are probably indicated regardless of the heart findings,” Dr. Wood said.

He added that low vitamin D produces secondary hyperparathyroidism, which exacerbates heart failure of any etiology. Because of this, thalassemia patients with ventricular dysfunction should have their vitamin D levels assessed, and replacement should be started if these levels are low.

The National Heart, Lung, and Blood Institute, the Centers for Disease Control and Prevention, and Novartis Pharma funded the study. Dr. Wood disclosed he receives research funding and honoraria from Novartis and Apotex, and is a consultant to Novartis.

Vitamin D might be worsening the cardiac iron overload and dysfunction by modulating calcium signaling. DR. WOOD

ATLANTA — Vitamin D deficiency was strongly associated with high cardiac iron and increased ventricular dysfunction in a retrospective review of 24 young thal-assemia major patients.

A review of their medical records showed levels of vitamin D(25[OH]D), the predominant circulating form of vitamin D, were “markedly depressed” in 13 patients and borderline depressed in the remaining patients, said Dr. John C. Wood of Children's Hospital Los Angeles and Keck School of Medicine at the University of Southern California, Los Angeles. There were 11 girls and 13 boys; mean age was 15 years.

Vitamin D(25[OH]D) levels less than 20 ng/mL are considered deficient and D(25[OH]D) levels 20–30 ng/mL are borderline or insufficient, Dr. Wood said in a presentation at the annual meeting of the American Society of Hematology. In this study, the mean D(25[OH]D) was 17 ng/mL.

The vitamin D levels were then compared with cardiac R2*–a surrogate MRI measure of the amount of iron in the heart—and left ventricular ejection fraction (LVEF) from each patient's most recent cardiac MRI. As vitamin D levels decreased, cardiac R2* increased. Vitamin D(25[OH]D) levels below 13 ng/mL were associated with severe cardiac iron loading. LVEF also decreased as D25-OH decreased.

“In our MRI laboratory, an ejection fraction less than 56% is considered abnormal and indicates poor pump function. In these patients, there was a proportional association between vitamin D(25[OH]D) levels and cardiac function. The four patients with the lowest D(25[OH]D) had an LVEF between 50% and 54%,” he said.

The population also was moderately iron overloaded, with mean ferritin levels of 2,089 ng/mL, liver iron 14 mg/g dry weight, transferrin saturation 84%, and cardiac R2* 65 Hz. The normal R2* should not exceed 50 Hz. “Vitamin D deficiency … is extremely common in thalassemia. Twenty-three of the 24 patients in our study had levels that are considered inadequate to ensure optimal calcium absorption and bone mineralization,” he said in an interview. Low vitamin D is linked to decreased cardiac function, muscle weakness, glucose insensitivity, and refractory congestive heart failure.

Increased iron in the heart becomes evident in children with thalassemia major around the age of 9 years. Two-thirds of adults with thalassemia have cardiac iron deposition. Iron cardiomyopathy is the leading cause of death in thalassemia. “Our study describes an association between low vitamin D, high cardiac iron, and increased ventricular dysfunction. We cannot prove [cause and effect], but vitamin D might be worsening the cardiac iron overload and the cardiac dysfunction through its modulation of calcium signaling in these patients.”

“Vitamin D deficiency is extremely common in thalassemia, and since osteoporosis is ubiquitous in this disease, vitamin D screening and replacement are probably indicated regardless of the heart findings,” Dr. Wood said.

He added that low vitamin D produces secondary hyperparathyroidism, which exacerbates heart failure of any etiology. Because of this, thalassemia patients with ventricular dysfunction should have their vitamin D levels assessed, and replacement should be started if these levels are low.

The National Heart, Lung, and Blood Institute, the Centers for Disease Control and Prevention, and Novartis Pharma funded the study. Dr. Wood disclosed he receives research funding and honoraria from Novartis and Apotex, and is a consultant to Novartis.

Vitamin D might be worsening the cardiac iron overload and dysfunction by modulating calcium signaling. DR. WOOD

ORLANDO — Early findings from the Aspirin Esomeprazole Chemoprevention Trial indicate that therapy with aspirin and esomeprazole is safe and well tolerated for preventing the progression of Barrett's esophagus to adenocarcinoma.

Since the start of the randomized Aspirin Esomeprazole Chemoprevention Trial (AspECT) in September 2005, 1,192 (83%) of the 1,436 patients have remained on their medication, and just 33 adverse events have been reported, said lead investigator Dr. Janusz Jankowski, professor of medicine, Oxford University (England), at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

AspECT is an ambitious, 10-year clinical trial being conducted in the United Kingdom. The trial's primary aim is to determine whether treatment with the proton pump inhibitor esomeprazole (Nexium, AstraZeneca) and aspirin can stop Barrett's metaplasia from progressing to adenocarcinoma. The investigators are also trying to determine whether this therapy will prevent or reduce myocardial infarction.

The United Kingdom is fertile ground for such a study, Dr. Jankowski said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

“The U.K. has the highest incidence of esophageal adenocarcinoma in the world—up to four times greater than that of other countries in Europe,” he said in an interview.

Being able to show that aspirin “is incredibly well tolerated” is very gratifying, Dr. Jankowski said, because many people were skeptical that it could be done. “People thought we were mad and dangerous, and that we would kill patients with low-dose aspirin.”

The first planned efficacy analysis is scheduled for 2010, and the final analysis is due in 2016. The trial is funded by Cancer Research UK, Oxford University, and AstraZeneca. Dr. Jankowski disclosed that he is a consultant to and receives research funding from AstraZeneca.

ORLANDO — Early findings from the Aspirin Esomeprazole Chemoprevention Trial indicate that therapy with aspirin and esomeprazole is safe and well tolerated for preventing the progression of Barrett's esophagus to adenocarcinoma.

Since the start of the randomized Aspirin Esomeprazole Chemoprevention Trial (AspECT) in September 2005, 1,192 (83%) of the 1,436 patients have remained on their medication, and just 33 adverse events have been reported, said lead investigator Dr. Janusz Jankowski, professor of medicine, Oxford University (England), at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

AspECT is an ambitious, 10-year clinical trial being conducted in the United Kingdom. The trial's primary aim is to determine whether treatment with the proton pump inhibitor esomeprazole (Nexium, AstraZeneca) and aspirin can stop Barrett's metaplasia from progressing to adenocarcinoma. The investigators are also trying to determine whether this therapy will prevent or reduce myocardial infarction.

The United Kingdom is fertile ground for such a study, Dr. Jankowski said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

“The U.K. has the highest incidence of esophageal adenocarcinoma in the world—up to four times greater than that of other countries in Europe,” he said in an interview.

Being able to show that aspirin “is incredibly well tolerated” is very gratifying, Dr. Jankowski said, because many people were skeptical that it could be done. “People thought we were mad and dangerous, and that we would kill patients with low-dose aspirin.”

The first planned efficacy analysis is scheduled for 2010, and the final analysis is due in 2016. The trial is funded by Cancer Research UK, Oxford University, and AstraZeneca. Dr. Jankowski disclosed that he is a consultant to and receives research funding from AstraZeneca.

ORLANDO — Early findings from the Aspirin Esomeprazole Chemoprevention Trial indicate that therapy with aspirin and esomeprazole is safe and well tolerated for preventing the progression of Barrett's esophagus to adenocarcinoma.

Since the start of the randomized Aspirin Esomeprazole Chemoprevention Trial (AspECT) in September 2005, 1,192 (83%) of the 1,436 patients have remained on their medication, and just 33 adverse events have been reported, said lead investigator Dr. Janusz Jankowski, professor of medicine, Oxford University (England), at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

AspECT is an ambitious, 10-year clinical trial being conducted in the United Kingdom. The trial's primary aim is to determine whether treatment with the proton pump inhibitor esomeprazole (Nexium, AstraZeneca) and aspirin can stop Barrett's metaplasia from progressing to adenocarcinoma. The investigators are also trying to determine whether this therapy will prevent or reduce myocardial infarction.

The United Kingdom is fertile ground for such a study, Dr. Jankowski said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

“The U.K. has the highest incidence of esophageal adenocarcinoma in the world—up to four times greater than that of other countries in Europe,” he said in an interview.

Being able to show that aspirin “is incredibly well tolerated” is very gratifying, Dr. Jankowski said, because many people were skeptical that it could be done. “People thought we were mad and dangerous, and that we would kill patients with low-dose aspirin.”

The first planned efficacy analysis is scheduled for 2010, and the final analysis is due in 2016. The trial is funded by Cancer Research UK, Oxford University, and AstraZeneca. Dr. Jankowski disclosed that he is a consultant to and receives research funding from AstraZeneca.