Jane Salodof MacNeil

ATLANTA — An annual dose of zoledronic acid can prevent bone loss in men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, Dr. M. Dror Michaelson reported at the annual meeting of the American Society of Clinical Oncology.

Investigators randomized 40 men who were being treated with gonadotropin-releasing hormone (GnRH) agonists to a single 4-mg intravenous dose of zoledronic acid (Zometa) or placebo.

Twelve months later, the men treated with zoledronic acid had average bone mineral density (BMD) increases of 4% in the lumbar spine and 0.7% in the total hip. The placebo group lost 3.1% of BMD in the lumbar spine and 1.9% in the total hip.

Two bone turnover markers, serum N-telopeptide and bone alkaline phosphatase, decreased during this same period in the men given zoledronic acid and increased in the placebo group. The differences were statistically significant.

“Annual zoledronic acid should be considered in GnRH-agonist treated men who may be at risk for osteoporosis,” Dr. Michaelson, of Massachusetts General Hospital Cancer Center, said on behalf of coinvestigators from his institution and the Dana-Farber Cancer Institute, both in Boston.

Dr. Michaelson said concern about side effects drew the group to explore annual dosing as an alternative to more frequent bisphosphonate use in these patients.

GnRH agonists are known to decrease bone mineral density while increasing bone turnover and fracture risk. Studies have shown that pamidronate as well as zoledronic acid can increase BMD in prostate cancer patients receiving hormonal therapy. Frequent bisphosphonate use can cause serious side effects, however, particularly renal insufficiency and osteonecrosis of the jaw. An annual dose of zoledronic acid had been shown to prevent bone loss in postmenopausal women, but Dr. Michaelson said the strategy had not been tested in men.

The trial excluded prostate cancer patients with metastatic bone disease, prostate-specific antigen evidence of progression, or osteoporosis. The men enrolled had an average age in the mid-60s. All patients in both arms of the study were encouraged to take daily supplements of calcium and vitamin D, Dr. Michaelson said.

In a discussion of the trial, Dr. Ian F. Tannock said the biomarkers were a reasonable surrogate end point for fracture risk. Although small, the trial probably was large enough to produce significant findings, he said, noting that the results are consistent with those of other studies. “I think those conclusions are reasonable,” said Dr. Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and the University of Toronto.

Estimating the cost of 4 mg of zoledronic acid to be about $600, he asked whether less-frequent dosing also could be effective in men with metastatic prostate cancer. “I think we should consider using that very expensive medication less often in that group of men, also,” he said.

Novartis Oncology and the Prostate Cancer Foundation supported the study.

ATLANTA — An annual dose of zoledronic acid can prevent bone loss in men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, Dr. M. Dror Michaelson reported at the annual meeting of the American Society of Clinical Oncology.

Investigators randomized 40 men who were being treated with gonadotropin-releasing hormone (GnRH) agonists to a single 4-mg intravenous dose of zoledronic acid (Zometa) or placebo.

Twelve months later, the men treated with zoledronic acid had average bone mineral density (BMD) increases of 4% in the lumbar spine and 0.7% in the total hip. The placebo group lost 3.1% of BMD in the lumbar spine and 1.9% in the total hip.

Two bone turnover markers, serum N-telopeptide and bone alkaline phosphatase, decreased during this same period in the men given zoledronic acid and increased in the placebo group. The differences were statistically significant.

“Annual zoledronic acid should be considered in GnRH-agonist treated men who may be at risk for osteoporosis,” Dr. Michaelson, of Massachusetts General Hospital Cancer Center, said on behalf of coinvestigators from his institution and the Dana-Farber Cancer Institute, both in Boston.

Dr. Michaelson said concern about side effects drew the group to explore annual dosing as an alternative to more frequent bisphosphonate use in these patients.

GnRH agonists are known to decrease bone mineral density while increasing bone turnover and fracture risk. Studies have shown that pamidronate as well as zoledronic acid can increase BMD in prostate cancer patients receiving hormonal therapy. Frequent bisphosphonate use can cause serious side effects, however, particularly renal insufficiency and osteonecrosis of the jaw. An annual dose of zoledronic acid had been shown to prevent bone loss in postmenopausal women, but Dr. Michaelson said the strategy had not been tested in men.

The trial excluded prostate cancer patients with metastatic bone disease, prostate-specific antigen evidence of progression, or osteoporosis. The men enrolled had an average age in the mid-60s. All patients in both arms of the study were encouraged to take daily supplements of calcium and vitamin D, Dr. Michaelson said.

In a discussion of the trial, Dr. Ian F. Tannock said the biomarkers were a reasonable surrogate end point for fracture risk. Although small, the trial probably was large enough to produce significant findings, he said, noting that the results are consistent with those of other studies. “I think those conclusions are reasonable,” said Dr. Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and the University of Toronto.

Estimating the cost of 4 mg of zoledronic acid to be about $600, he asked whether less-frequent dosing also could be effective in men with metastatic prostate cancer. “I think we should consider using that very expensive medication less often in that group of men, also,” he said.

Novartis Oncology and the Prostate Cancer Foundation supported the study.

ATLANTA — An annual dose of zoledronic acid can prevent bone loss in men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer, Dr. M. Dror Michaelson reported at the annual meeting of the American Society of Clinical Oncology.

Investigators randomized 40 men who were being treated with gonadotropin-releasing hormone (GnRH) agonists to a single 4-mg intravenous dose of zoledronic acid (Zometa) or placebo.

Twelve months later, the men treated with zoledronic acid had average bone mineral density (BMD) increases of 4% in the lumbar spine and 0.7% in the total hip. The placebo group lost 3.1% of BMD in the lumbar spine and 1.9% in the total hip.

Two bone turnover markers, serum N-telopeptide and bone alkaline phosphatase, decreased during this same period in the men given zoledronic acid and increased in the placebo group. The differences were statistically significant.

“Annual zoledronic acid should be considered in GnRH-agonist treated men who may be at risk for osteoporosis,” Dr. Michaelson, of Massachusetts General Hospital Cancer Center, said on behalf of coinvestigators from his institution and the Dana-Farber Cancer Institute, both in Boston.

Dr. Michaelson said concern about side effects drew the group to explore annual dosing as an alternative to more frequent bisphosphonate use in these patients.

GnRH agonists are known to decrease bone mineral density while increasing bone turnover and fracture risk. Studies have shown that pamidronate as well as zoledronic acid can increase BMD in prostate cancer patients receiving hormonal therapy. Frequent bisphosphonate use can cause serious side effects, however, particularly renal insufficiency and osteonecrosis of the jaw. An annual dose of zoledronic acid had been shown to prevent bone loss in postmenopausal women, but Dr. Michaelson said the strategy had not been tested in men.

The trial excluded prostate cancer patients with metastatic bone disease, prostate-specific antigen evidence of progression, or osteoporosis. The men enrolled had an average age in the mid-60s. All patients in both arms of the study were encouraged to take daily supplements of calcium and vitamin D, Dr. Michaelson said.

In a discussion of the trial, Dr. Ian F. Tannock said the biomarkers were a reasonable surrogate end point for fracture risk. Although small, the trial probably was large enough to produce significant findings, he said, noting that the results are consistent with those of other studies. “I think those conclusions are reasonable,” said Dr. Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and the University of Toronto.

Estimating the cost of 4 mg of zoledronic acid to be about $600, he asked whether less-frequent dosing also could be effective in men with metastatic prostate cancer. “I think we should consider using that very expensive medication less often in that group of men, also,” he said.

Novartis Oncology and the Prostate Cancer Foundation supported the study.

ATLANTA — Updated results from a clinical trial that helped establish adjuvant chemotherapy with paclitaxel and carboplatin as the standard of care for stage IB non-small cell lung cancer no longer show a significant improvement in overall survival.

At a median follow-up of 57 months, 5-year overall survival was 59% for adjuvant chemotherapy patients and 57% for those randomized to observation in the Cancer and Leukemia Group B (CALGB) trial known as CALGB 9633. The 2% difference was not statistically significant.

Patients given adjuvant chemotherapy did benefit from significantly improved 2- and 3-year survival in the new analysis. They also had a significantly longer failure-free survival duration, with a hazard ratio of 0.74. Dr. Gary M. Strauss reported the new data on behalf of CALGB at the annual meeting of the American Society of Clinical Oncology (ASCO). Despite some positive effects, CALGB 9633 “can be interpreted as a negative study and, perhaps I should say, should be interpreted as a negative study,” he said.

In a shift from his presentation 2 years ago at the same meeting, Dr. Strauss of Brown University, Providence, R.I., said that “the results of CALGB 9633 do not mandate adjuvant chemotherapy as the standard of care in all stage IB patients.” The results do, however, support continued consideration of adjuvant paclitaxel and carboplatin for stage IB patients, in particular, those with tumors 4 cm or more in diameter.

CALGB 9633 had been the only trial among three influential adjuvant therapy studies to report a survival advantage in NSCLC patients with stage IB tumors. At the ASCO meeting 2 years ago, Dr. Strauss reported an 8% improvement in survival with adjuvant chemotherapy (hazard ratio 0.62). A data safety monitoring board closed the trial early because its primary outcome had been reached.

The early stopping was justified but “potentially problematic,” Dr. Strauss said. It did not negate the earlier results, but it left the study without sufficient statistical power to detect “smaller differences that are nonetheless clinically significant,” he added.

Investigators had already revamped CALGB 9633 from an initial goal of 500 patients to a target of 384 patients because of slow accrual.

After complete resection of their tumors, 171 patients were randomized to observation and 173 patients to four cycles during each of which they received 200 mg/m

As of April 19, 2006, the latest data cutoff, median overall survival was 95 months for patients who had received adjuvant chemotherapy and 78 months with observation. Though the hazard ratio was 0.80, the difference was not statistically significant. Overall survival was significantly better for the adjuvant chemotherapy arm at 2 years (90% vs. 84% for the control arm) and at 3 years (79% vs. 71%), but not thereafter.

Failure-free survival favored adjuvant chemotherapy, with a median of 89 months vs. 52 months in the observation arm. The difference was significant at 3 years, when 66% of the adjuvant arm but only 57% of the observation arm had no recurrence.

In an unplanned subset analysis reported by Dr. Strauss, the investigators did find a significant survival benefit for patients whose tumors were 4 cm or larger in diameter (hazard ratio 0.66), but not for those with smaller tumors.

As only 137 of 155 deaths required for final analysis have so far been observed, Dr. Strauss emphasized that the new report is still only a preliminary analysis. In conclusion, he said the significant advantages in 3-year and in disease-free survival suggest that the regimen is effective and may delay recurrence, even if it does not enhance the likelihood of a cure.

ATLANTA — Updated results from a clinical trial that helped establish adjuvant chemotherapy with paclitaxel and carboplatin as the standard of care for stage IB non-small cell lung cancer no longer show a significant improvement in overall survival.

At a median follow-up of 57 months, 5-year overall survival was 59% for adjuvant chemotherapy patients and 57% for those randomized to observation in the Cancer and Leukemia Group B (CALGB) trial known as CALGB 9633. The 2% difference was not statistically significant.

Patients given adjuvant chemotherapy did benefit from significantly improved 2- and 3-year survival in the new analysis. They also had a significantly longer failure-free survival duration, with a hazard ratio of 0.74. Dr. Gary M. Strauss reported the new data on behalf of CALGB at the annual meeting of the American Society of Clinical Oncology (ASCO). Despite some positive effects, CALGB 9633 “can be interpreted as a negative study and, perhaps I should say, should be interpreted as a negative study,” he said.

In a shift from his presentation 2 years ago at the same meeting, Dr. Strauss of Brown University, Providence, R.I., said that “the results of CALGB 9633 do not mandate adjuvant chemotherapy as the standard of care in all stage IB patients.” The results do, however, support continued consideration of adjuvant paclitaxel and carboplatin for stage IB patients, in particular, those with tumors 4 cm or more in diameter.

CALGB 9633 had been the only trial among three influential adjuvant therapy studies to report a survival advantage in NSCLC patients with stage IB tumors. At the ASCO meeting 2 years ago, Dr. Strauss reported an 8% improvement in survival with adjuvant chemotherapy (hazard ratio 0.62). A data safety monitoring board closed the trial early because its primary outcome had been reached.

The early stopping was justified but “potentially problematic,” Dr. Strauss said. It did not negate the earlier results, but it left the study without sufficient statistical power to detect “smaller differences that are nonetheless clinically significant,” he added.

Investigators had already revamped CALGB 9633 from an initial goal of 500 patients to a target of 384 patients because of slow accrual.

After complete resection of their tumors, 171 patients were randomized to observation and 173 patients to four cycles during each of which they received 200 mg/m

As of April 19, 2006, the latest data cutoff, median overall survival was 95 months for patients who had received adjuvant chemotherapy and 78 months with observation. Though the hazard ratio was 0.80, the difference was not statistically significant. Overall survival was significantly better for the adjuvant chemotherapy arm at 2 years (90% vs. 84% for the control arm) and at 3 years (79% vs. 71%), but not thereafter.

Failure-free survival favored adjuvant chemotherapy, with a median of 89 months vs. 52 months in the observation arm. The difference was significant at 3 years, when 66% of the adjuvant arm but only 57% of the observation arm had no recurrence.

In an unplanned subset analysis reported by Dr. Strauss, the investigators did find a significant survival benefit for patients whose tumors were 4 cm or larger in diameter (hazard ratio 0.66), but not for those with smaller tumors.

As only 137 of 155 deaths required for final analysis have so far been observed, Dr. Strauss emphasized that the new report is still only a preliminary analysis. In conclusion, he said the significant advantages in 3-year and in disease-free survival suggest that the regimen is effective and may delay recurrence, even if it does not enhance the likelihood of a cure.

ATLANTA — Updated results from a clinical trial that helped establish adjuvant chemotherapy with paclitaxel and carboplatin as the standard of care for stage IB non-small cell lung cancer no longer show a significant improvement in overall survival.

At a median follow-up of 57 months, 5-year overall survival was 59% for adjuvant chemotherapy patients and 57% for those randomized to observation in the Cancer and Leukemia Group B (CALGB) trial known as CALGB 9633. The 2% difference was not statistically significant.

Patients given adjuvant chemotherapy did benefit from significantly improved 2- and 3-year survival in the new analysis. They also had a significantly longer failure-free survival duration, with a hazard ratio of 0.74. Dr. Gary M. Strauss reported the new data on behalf of CALGB at the annual meeting of the American Society of Clinical Oncology (ASCO). Despite some positive effects, CALGB 9633 “can be interpreted as a negative study and, perhaps I should say, should be interpreted as a negative study,” he said.

In a shift from his presentation 2 years ago at the same meeting, Dr. Strauss of Brown University, Providence, R.I., said that “the results of CALGB 9633 do not mandate adjuvant chemotherapy as the standard of care in all stage IB patients.” The results do, however, support continued consideration of adjuvant paclitaxel and carboplatin for stage IB patients, in particular, those with tumors 4 cm or more in diameter.

CALGB 9633 had been the only trial among three influential adjuvant therapy studies to report a survival advantage in NSCLC patients with stage IB tumors. At the ASCO meeting 2 years ago, Dr. Strauss reported an 8% improvement in survival with adjuvant chemotherapy (hazard ratio 0.62). A data safety monitoring board closed the trial early because its primary outcome had been reached.

The early stopping was justified but “potentially problematic,” Dr. Strauss said. It did not negate the earlier results, but it left the study without sufficient statistical power to detect “smaller differences that are nonetheless clinically significant,” he added.

Investigators had already revamped CALGB 9633 from an initial goal of 500 patients to a target of 384 patients because of slow accrual.

After complete resection of their tumors, 171 patients were randomized to observation and 173 patients to four cycles during each of which they received 200 mg/m

As of April 19, 2006, the latest data cutoff, median overall survival was 95 months for patients who had received adjuvant chemotherapy and 78 months with observation. Though the hazard ratio was 0.80, the difference was not statistically significant. Overall survival was significantly better for the adjuvant chemotherapy arm at 2 years (90% vs. 84% for the control arm) and at 3 years (79% vs. 71%), but not thereafter.

Failure-free survival favored adjuvant chemotherapy, with a median of 89 months vs. 52 months in the observation arm. The difference was significant at 3 years, when 66% of the adjuvant arm but only 57% of the observation arm had no recurrence.

In an unplanned subset analysis reported by Dr. Strauss, the investigators did find a significant survival benefit for patients whose tumors were 4 cm or larger in diameter (hazard ratio 0.66), but not for those with smaller tumors.

As only 137 of 155 deaths required for final analysis have so far been observed, Dr. Strauss emphasized that the new report is still only a preliminary analysis. In conclusion, he said the significant advantages in 3-year and in disease-free survival suggest that the regimen is effective and may delay recurrence, even if it does not enhance the likelihood of a cure.

ATLANTA — Bevacizumab (Avastin) in combination with erlotinib (Tarceva) was associated with promising preliminary results in the treatment of refractory non-small cell lung cancer in data presented at the annual meeting of the American Society of Clinical Oncology.

The 17.9% response rate with the bevacizumab-erlotinib combination was better than the 12.5% rate seen in patients treated with bevacizumab and chemotherapy and the 12.2% rate seen in those treated with chemotherapy alone.

Dr. Louis Fehrenbacher reported that 31 of 39 patients treated with bevacizumab and erlotinib were alive at 6 months. With bevacizumab and chemotherapy, 29 of 40 were still alive at 6 months.

The two bevacizumab arms also had similar progression-free survival: 4.8 months when the angiogenesis inhibitor was combined with chemotherapy and 4.4 months when it was used with erlotinib.

A control arm of 41 patients treated only with chemotherapy (either pemetrexed or docetaxel) had the worst outcomes. Only 26 of those patients were alive at 6 months. The median length of progression-free survival was just 3 months.

Dr. Fehrenbacher of Kaiser Permanente Vallejo (Calif.) Medical Center and his coinvestigators reported that about one-third of both bevacizumab arms and about one-fifth of the chemotherapy-only patients were progression-free at 6 months. The investigators calculated adjusted hazard ratios of 0.66 for bevacizumab with chemotherapy and 0.72 for bevacizumab with erlotinib, compared with the chemotherapy arm.

“Overall I think this is a very encouraging finding that the [bevacizumab-erlotinib] combination may actually work in a refractory situation,” Dr. Tony Mok said in a discussion of the poster. Dr. Mok of the Chinese University of Hong Kong said the results challenge the belief that combining agents is not worthwhile for second-line treatment of non-small cell lung cancer.

The findings also raise questions, he said, about how bevacizumab works and how bevacizumab and chemotherapy work together. Instead of treating chemotherapies as interchangeable with bevacizumab, he said, clinicians need to find the best combination.

One-year data are not yet available for the trial, which enrolled patients with locally advanced or metastatic (stages IIb-IV), nonsquamous, non-small cell lung cancer. The study excluded patients with brain metastases.

Bevacizumab, a monoclonal antibody marketed by Genentech in the United States and by Roche worldwide, helps to cut off blood supply to tumors by inhibiting vascular endothelial growth factor.

Erlotinib, produced by OSI Pharmaceuticals, targets the human epidermal growth factor receptor pathway, which also plays a role in promoting tumor growth. It is approved for use as monotherapy in patients with locally advanced or metastatic non-small cell lung cancer that has progressed on chemotherapy.

Beyond the juggling of similar benefits in the two bevacizumab arms, the much-anticipated phase II trial showed less toxicity overall when patients were treated with two targeted therapies instead of chemotherapy alone or in combination.

Only four patients (10%) in the bevacizumab-erlotinib arm stopped treatment due to adverse events, compared with 10 patients in each of the chemotherapy arms. The trial reported serious events in 13 bevacizumab-erlotinib patients (33%), 16 bevacizumab-chemotherapy patients (40%), and 22 chemotherapy-only patients (54%).

One chemotherapy-only patient died of cardiopulmonary arrest. No chemotherapy-only patients had pulmonary hemorrhage, a growing concern for patients treated with angiogenic inhibitors. Two fatal pulmonary hemorrhages and a fatal gastrointestinal bleed occurred in patients treated with bevacizumab and chemotherapy. One patient in the bevacizumab-erlotinib arm died of a pulmonary hemorrhage.

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — Bevacizumab (Avastin) in combination with erlotinib (Tarceva) was associated with promising preliminary results in the treatment of refractory non-small cell lung cancer in data presented at the annual meeting of the American Society of Clinical Oncology.

The 17.9% response rate with the bevacizumab-erlotinib combination was better than the 12.5% rate seen in patients treated with bevacizumab and chemotherapy and the 12.2% rate seen in those treated with chemotherapy alone.

Dr. Louis Fehrenbacher reported that 31 of 39 patients treated with bevacizumab and erlotinib were alive at 6 months. With bevacizumab and chemotherapy, 29 of 40 were still alive at 6 months.

The two bevacizumab arms also had similar progression-free survival: 4.8 months when the angiogenesis inhibitor was combined with chemotherapy and 4.4 months when it was used with erlotinib.

A control arm of 41 patients treated only with chemotherapy (either pemetrexed or docetaxel) had the worst outcomes. Only 26 of those patients were alive at 6 months. The median length of progression-free survival was just 3 months.

Dr. Fehrenbacher of Kaiser Permanente Vallejo (Calif.) Medical Center and his coinvestigators reported that about one-third of both bevacizumab arms and about one-fifth of the chemotherapy-only patients were progression-free at 6 months. The investigators calculated adjusted hazard ratios of 0.66 for bevacizumab with chemotherapy and 0.72 for bevacizumab with erlotinib, compared with the chemotherapy arm.

“Overall I think this is a very encouraging finding that the [bevacizumab-erlotinib] combination may actually work in a refractory situation,” Dr. Tony Mok said in a discussion of the poster. Dr. Mok of the Chinese University of Hong Kong said the results challenge the belief that combining agents is not worthwhile for second-line treatment of non-small cell lung cancer.

The findings also raise questions, he said, about how bevacizumab works and how bevacizumab and chemotherapy work together. Instead of treating chemotherapies as interchangeable with bevacizumab, he said, clinicians need to find the best combination.

One-year data are not yet available for the trial, which enrolled patients with locally advanced or metastatic (stages IIb-IV), nonsquamous, non-small cell lung cancer. The study excluded patients with brain metastases.

Bevacizumab, a monoclonal antibody marketed by Genentech in the United States and by Roche worldwide, helps to cut off blood supply to tumors by inhibiting vascular endothelial growth factor.

Erlotinib, produced by OSI Pharmaceuticals, targets the human epidermal growth factor receptor pathway, which also plays a role in promoting tumor growth. It is approved for use as monotherapy in patients with locally advanced or metastatic non-small cell lung cancer that has progressed on chemotherapy.

Beyond the juggling of similar benefits in the two bevacizumab arms, the much-anticipated phase II trial showed less toxicity overall when patients were treated with two targeted therapies instead of chemotherapy alone or in combination.

Only four patients (10%) in the bevacizumab-erlotinib arm stopped treatment due to adverse events, compared with 10 patients in each of the chemotherapy arms. The trial reported serious events in 13 bevacizumab-erlotinib patients (33%), 16 bevacizumab-chemotherapy patients (40%), and 22 chemotherapy-only patients (54%).

One chemotherapy-only patient died of cardiopulmonary arrest. No chemotherapy-only patients had pulmonary hemorrhage, a growing concern for patients treated with angiogenic inhibitors. Two fatal pulmonary hemorrhages and a fatal gastrointestinal bleed occurred in patients treated with bevacizumab and chemotherapy. One patient in the bevacizumab-erlotinib arm died of a pulmonary hemorrhage.

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — Bevacizumab (Avastin) in combination with erlotinib (Tarceva) was associated with promising preliminary results in the treatment of refractory non-small cell lung cancer in data presented at the annual meeting of the American Society of Clinical Oncology.

The 17.9% response rate with the bevacizumab-erlotinib combination was better than the 12.5% rate seen in patients treated with bevacizumab and chemotherapy and the 12.2% rate seen in those treated with chemotherapy alone.

Dr. Louis Fehrenbacher reported that 31 of 39 patients treated with bevacizumab and erlotinib were alive at 6 months. With bevacizumab and chemotherapy, 29 of 40 were still alive at 6 months.

The two bevacizumab arms also had similar progression-free survival: 4.8 months when the angiogenesis inhibitor was combined with chemotherapy and 4.4 months when it was used with erlotinib.

A control arm of 41 patients treated only with chemotherapy (either pemetrexed or docetaxel) had the worst outcomes. Only 26 of those patients were alive at 6 months. The median length of progression-free survival was just 3 months.

Dr. Fehrenbacher of Kaiser Permanente Vallejo (Calif.) Medical Center and his coinvestigators reported that about one-third of both bevacizumab arms and about one-fifth of the chemotherapy-only patients were progression-free at 6 months. The investigators calculated adjusted hazard ratios of 0.66 for bevacizumab with chemotherapy and 0.72 for bevacizumab with erlotinib, compared with the chemotherapy arm.

“Overall I think this is a very encouraging finding that the [bevacizumab-erlotinib] combination may actually work in a refractory situation,” Dr. Tony Mok said in a discussion of the poster. Dr. Mok of the Chinese University of Hong Kong said the results challenge the belief that combining agents is not worthwhile for second-line treatment of non-small cell lung cancer.

The findings also raise questions, he said, about how bevacizumab works and how bevacizumab and chemotherapy work together. Instead of treating chemotherapies as interchangeable with bevacizumab, he said, clinicians need to find the best combination.

One-year data are not yet available for the trial, which enrolled patients with locally advanced or metastatic (stages IIb-IV), nonsquamous, non-small cell lung cancer. The study excluded patients with brain metastases.

Bevacizumab, a monoclonal antibody marketed by Genentech in the United States and by Roche worldwide, helps to cut off blood supply to tumors by inhibiting vascular endothelial growth factor.

Erlotinib, produced by OSI Pharmaceuticals, targets the human epidermal growth factor receptor pathway, which also plays a role in promoting tumor growth. It is approved for use as monotherapy in patients with locally advanced or metastatic non-small cell lung cancer that has progressed on chemotherapy.

Beyond the juggling of similar benefits in the two bevacizumab arms, the much-anticipated phase II trial showed less toxicity overall when patients were treated with two targeted therapies instead of chemotherapy alone or in combination.

Only four patients (10%) in the bevacizumab-erlotinib arm stopped treatment due to adverse events, compared with 10 patients in each of the chemotherapy arms. The trial reported serious events in 13 bevacizumab-erlotinib patients (33%), 16 bevacizumab-chemotherapy patients (40%), and 22 chemotherapy-only patients (54%).

One chemotherapy-only patient died of cardiopulmonary arrest. No chemotherapy-only patients had pulmonary hemorrhage, a growing concern for patients treated with angiogenic inhibitors. Two fatal pulmonary hemorrhages and a fatal gastrointestinal bleed occurred in patients treated with bevacizumab and chemotherapy. One patient in the bevacizumab-erlotinib arm died of a pulmonary hemorrhage.

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — A year after research on bevacizumab proved that angiogenesis inhibition can help patients with non-small cell lung cancer live longer, a second generation of antiangiogenesis agents is showing activity against advanced, metastatic lung cancer.

Phase II trials of sunitinib (Sutent), sorafenib (Nexavar), and an experimental drug called ZD6474 (Zactima) all reported progression-free survival rates of 11% or more at the annual meeting of the American Society of Clinical Oncology.

Because each drug hits more cellular targets than does bevacizumab (Avastin), investigators voiced hope that the new agents will be more effective. Two of the drugs—sunitinib and sorafenib—have already been approved for renal cell carcinoma. Sunitinib also has an indication for gastrointestinal stromal tumors that are refractory to imatinib (Gleevec).

Along with the possibility of better therapies, however, the three trials renewed concerns about the toxicity of antiangiogenic agents. Investigators reported cavitation and hemorrhage leading to treatment-related deaths. Rash, hand-foot syndrome, and controllable hypertension also were seen.

“More than ever, we need pulmonologists to look at the risk of bleeding and to look at cavitation,” Dr. Roy S. Herbst said in an interview after presenting a review of the new drugs and the state of antiangiogenic therapy against lung cancer.

“We need to find some sort of risk factors to stratify these patients,” said Dr. Herbst, of the department of thoracic/head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston and the senior investigator of a series of lung cancer trials testing the combination of bevacizumab and erlotinib (Tarceva).

Dr. Herbst cited the survival advantages reported last year in a phase III trial combining bevacizumab with chemotherapy, as well as early results from his study. “Despite these advances, few, if any, metastatic patients are cured,” he cautioned.

He called the three new agents “quite comparable” and noted that “signs of early activity are seen,” but said that whether the new multitargeted tyrosine kinase inhibitors are more effective than single-targeted bevacizumab is “not clear yet” in non-small cell lung cancer.

Among the potential advantages of multitargeted agents, Dr. Herbst cited convenience, single-agent activity, the ability to act on both tumor and blood vessels, and the potential to lower the cost of treatment. Whether these agents can be used alone or should be combined with chemotherapy or other targeted agents still has to be worked out in clinical trials, he said.

“Angiogenesis inhibition has become a mainstay in cancer therapy, and it will be very interesting in the next few years as we figure out how to optimize its use and use it safely,” Dr. Herbst said. “It is a perfect therapy to add to our existing methods.”

Sunitinib

Dr. Mark A. Socinski reported that sunitinib controlled tumor growth in more than half of 63 patients who had failed previous regimens for advanced non-small cell lung cancer. Six patients (9.5%) had partial responses, and 27 patients (42.9%) had stable disease in the study. Median progression-free survival reached 11.3 weeks, and overall survival was 23.9 weeks.

Three patients died of hemorrhages, however: Two were pulmonary—only one of which was attributed to treatment—and one was cerebral. Fatigue led the list of grades III and IV toxicity. Other adverse events included myalgia, neutropenia, stomatitis, headaches, and hypertension.

Patients received 50 mg of sunitinib daily for 4 weeks followed by 2 weeks off therapy before starting another cycle in the trial. Dr. Socinski, director of the multidisciplinary thoracic oncology program at the University of North Carolina at Chapel Hill, announced that the study has been extended with a revised dosing schedule of 37.5 mg daily.

Sorafenib

Dr. Ulrich Gatzemeier reported that 30 (59%) of 51 patients with advanced non-small cell lung cancer had stable disease while they were treated with 400 mg twice a day of sorafenib. No partial responses were recorded in the study.

Another 18 patients (35%) progressed, and 3 patients died before they could be evaluated. Median progression-free survival reached 11.3 months, and median survival 29.5 weeks. Two patients have been on therapy for 2 years, according to Dr. Gatzemeier, head of thoracic oncology at Grosshansdorf Hospital in Hamburg, Germany.

Four patients, all with squamous cell carcinoma, had tumor cavitation, and four patients had bleeding events. Three hemorrhages were described as minor, but a fatal hemorrhage occurred in a cavitary lesion while the patient was receiving radiation therapy 30 days after stopping sorafenib. Other adverse events included diarrhea, hand-foot syndrome, fatigue, and hypertension.

Dr. Gatzemeier said that a phase III trial has already started. It is to randomize 900 patients to a carboplatin/paclitaxel regimen with sorafenib or a placebo.

ZD6474

Dr. Ronald B. Natale reported that 83 patients achieved a median progression-free survival of 11 weeks on 300 mg per day of ZD6474. In comparison, only 8.1 weeks was reached by a control arm of 85 patients treated with 250 mg of gefitinib (Iressa) daily. The response rates were 8% and 1%, respectively.

The trial allowed patients who had progressed to cross over to the other agent. There were no additional responses, but 16 of 37 patients who switched from gefitinib to ZD6474 achieved more than 8 weeks' disease control vs. 7 of 29 patients who switched to gefitinib from ZD6474.

Overall survival, however, showed a trend in favor of starting on gefitinib: The median was 7.4 months vs. 6.1 months for those who began on ZD6474.

Adverse events included diarrhea, rash, asymptomatic QTc prolongation, and hypertension, but not hemoptysis.

Dr. Natale, a medical oncologist at the Cedars-Sinai Comprehensive Cancer Center in Los Angeles, concluded that the data support further investigation of ZD6474 as monotherapy.

ATLANTA — A year after research on bevacizumab proved that angiogenesis inhibition can help patients with non-small cell lung cancer live longer, a second generation of antiangiogenesis agents is showing activity against advanced, metastatic lung cancer.

Phase II trials of sunitinib (Sutent), sorafenib (Nexavar), and an experimental drug called ZD6474 (Zactima) all reported progression-free survival rates of 11% or more at the annual meeting of the American Society of Clinical Oncology.

Because each drug hits more cellular targets than does bevacizumab (Avastin), investigators voiced hope that the new agents will be more effective. Two of the drugs—sunitinib and sorafenib—have already been approved for renal cell carcinoma. Sunitinib also has an indication for gastrointestinal stromal tumors that are refractory to imatinib (Gleevec).

Along with the possibility of better therapies, however, the three trials renewed concerns about the toxicity of antiangiogenic agents. Investigators reported cavitation and hemorrhage leading to treatment-related deaths. Rash, hand-foot syndrome, and controllable hypertension also were seen.

“More than ever, we need pulmonologists to look at the risk of bleeding and to look at cavitation,” Dr. Roy S. Herbst said in an interview after presenting a review of the new drugs and the state of antiangiogenic therapy against lung cancer.

“We need to find some sort of risk factors to stratify these patients,” said Dr. Herbst, of the department of thoracic/head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston and the senior investigator of a series of lung cancer trials testing the combination of bevacizumab and erlotinib (Tarceva).

Dr. Herbst cited the survival advantages reported last year in a phase III trial combining bevacizumab with chemotherapy, as well as early results from his study. “Despite these advances, few, if any, metastatic patients are cured,” he cautioned.

He called the three new agents “quite comparable” and noted that “signs of early activity are seen,” but said that whether the new multitargeted tyrosine kinase inhibitors are more effective than single-targeted bevacizumab is “not clear yet” in non-small cell lung cancer.

Among the potential advantages of multitargeted agents, Dr. Herbst cited convenience, single-agent activity, the ability to act on both tumor and blood vessels, and the potential to lower the cost of treatment. Whether these agents can be used alone or should be combined with chemotherapy or other targeted agents still has to be worked out in clinical trials, he said.

“Angiogenesis inhibition has become a mainstay in cancer therapy, and it will be very interesting in the next few years as we figure out how to optimize its use and use it safely,” Dr. Herbst said. “It is a perfect therapy to add to our existing methods.”

Sunitinib

Dr. Mark A. Socinski reported that sunitinib controlled tumor growth in more than half of 63 patients who had failed previous regimens for advanced non-small cell lung cancer. Six patients (9.5%) had partial responses, and 27 patients (42.9%) had stable disease in the study. Median progression-free survival reached 11.3 weeks, and overall survival was 23.9 weeks.

Three patients died of hemorrhages, however: Two were pulmonary—only one of which was attributed to treatment—and one was cerebral. Fatigue led the list of grades III and IV toxicity. Other adverse events included myalgia, neutropenia, stomatitis, headaches, and hypertension.

Patients received 50 mg of sunitinib daily for 4 weeks followed by 2 weeks off therapy before starting another cycle in the trial. Dr. Socinski, director of the multidisciplinary thoracic oncology program at the University of North Carolina at Chapel Hill, announced that the study has been extended with a revised dosing schedule of 37.5 mg daily.

Sorafenib

Dr. Ulrich Gatzemeier reported that 30 (59%) of 51 patients with advanced non-small cell lung cancer had stable disease while they were treated with 400 mg twice a day of sorafenib. No partial responses were recorded in the study.

Another 18 patients (35%) progressed, and 3 patients died before they could be evaluated. Median progression-free survival reached 11.3 months, and median survival 29.5 weeks. Two patients have been on therapy for 2 years, according to Dr. Gatzemeier, head of thoracic oncology at Grosshansdorf Hospital in Hamburg, Germany.

Four patients, all with squamous cell carcinoma, had tumor cavitation, and four patients had bleeding events. Three hemorrhages were described as minor, but a fatal hemorrhage occurred in a cavitary lesion while the patient was receiving radiation therapy 30 days after stopping sorafenib. Other adverse events included diarrhea, hand-foot syndrome, fatigue, and hypertension.

Dr. Gatzemeier said that a phase III trial has already started. It is to randomize 900 patients to a carboplatin/paclitaxel regimen with sorafenib or a placebo.

ZD6474

Dr. Ronald B. Natale reported that 83 patients achieved a median progression-free survival of 11 weeks on 300 mg per day of ZD6474. In comparison, only 8.1 weeks was reached by a control arm of 85 patients treated with 250 mg of gefitinib (Iressa) daily. The response rates were 8% and 1%, respectively.

The trial allowed patients who had progressed to cross over to the other agent. There were no additional responses, but 16 of 37 patients who switched from gefitinib to ZD6474 achieved more than 8 weeks' disease control vs. 7 of 29 patients who switched to gefitinib from ZD6474.

Overall survival, however, showed a trend in favor of starting on gefitinib: The median was 7.4 months vs. 6.1 months for those who began on ZD6474.

Adverse events included diarrhea, rash, asymptomatic QTc prolongation, and hypertension, but not hemoptysis.

Dr. Natale, a medical oncologist at the Cedars-Sinai Comprehensive Cancer Center in Los Angeles, concluded that the data support further investigation of ZD6474 as monotherapy.

ATLANTA — A year after research on bevacizumab proved that angiogenesis inhibition can help patients with non-small cell lung cancer live longer, a second generation of antiangiogenesis agents is showing activity against advanced, metastatic lung cancer.

Phase II trials of sunitinib (Sutent), sorafenib (Nexavar), and an experimental drug called ZD6474 (Zactima) all reported progression-free survival rates of 11% or more at the annual meeting of the American Society of Clinical Oncology.

Because each drug hits more cellular targets than does bevacizumab (Avastin), investigators voiced hope that the new agents will be more effective. Two of the drugs—sunitinib and sorafenib—have already been approved for renal cell carcinoma. Sunitinib also has an indication for gastrointestinal stromal tumors that are refractory to imatinib (Gleevec).

Along with the possibility of better therapies, however, the three trials renewed concerns about the toxicity of antiangiogenic agents. Investigators reported cavitation and hemorrhage leading to treatment-related deaths. Rash, hand-foot syndrome, and controllable hypertension also were seen.

“More than ever, we need pulmonologists to look at the risk of bleeding and to look at cavitation,” Dr. Roy S. Herbst said in an interview after presenting a review of the new drugs and the state of antiangiogenic therapy against lung cancer.

“We need to find some sort of risk factors to stratify these patients,” said Dr. Herbst, of the department of thoracic/head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston and the senior investigator of a series of lung cancer trials testing the combination of bevacizumab and erlotinib (Tarceva).

Dr. Herbst cited the survival advantages reported last year in a phase III trial combining bevacizumab with chemotherapy, as well as early results from his study. “Despite these advances, few, if any, metastatic patients are cured,” he cautioned.

He called the three new agents “quite comparable” and noted that “signs of early activity are seen,” but said that whether the new multitargeted tyrosine kinase inhibitors are more effective than single-targeted bevacizumab is “not clear yet” in non-small cell lung cancer.

Among the potential advantages of multitargeted agents, Dr. Herbst cited convenience, single-agent activity, the ability to act on both tumor and blood vessels, and the potential to lower the cost of treatment. Whether these agents can be used alone or should be combined with chemotherapy or other targeted agents still has to be worked out in clinical trials, he said.

“Angiogenesis inhibition has become a mainstay in cancer therapy, and it will be very interesting in the next few years as we figure out how to optimize its use and use it safely,” Dr. Herbst said. “It is a perfect therapy to add to our existing methods.”

Sunitinib

Dr. Mark A. Socinski reported that sunitinib controlled tumor growth in more than half of 63 patients who had failed previous regimens for advanced non-small cell lung cancer. Six patients (9.5%) had partial responses, and 27 patients (42.9%) had stable disease in the study. Median progression-free survival reached 11.3 weeks, and overall survival was 23.9 weeks.

Three patients died of hemorrhages, however: Two were pulmonary—only one of which was attributed to treatment—and one was cerebral. Fatigue led the list of grades III and IV toxicity. Other adverse events included myalgia, neutropenia, stomatitis, headaches, and hypertension.

Patients received 50 mg of sunitinib daily for 4 weeks followed by 2 weeks off therapy before starting another cycle in the trial. Dr. Socinski, director of the multidisciplinary thoracic oncology program at the University of North Carolina at Chapel Hill, announced that the study has been extended with a revised dosing schedule of 37.5 mg daily.

Sorafenib

Dr. Ulrich Gatzemeier reported that 30 (59%) of 51 patients with advanced non-small cell lung cancer had stable disease while they were treated with 400 mg twice a day of sorafenib. No partial responses were recorded in the study.

Another 18 patients (35%) progressed, and 3 patients died before they could be evaluated. Median progression-free survival reached 11.3 months, and median survival 29.5 weeks. Two patients have been on therapy for 2 years, according to Dr. Gatzemeier, head of thoracic oncology at Grosshansdorf Hospital in Hamburg, Germany.

Four patients, all with squamous cell carcinoma, had tumor cavitation, and four patients had bleeding events. Three hemorrhages were described as minor, but a fatal hemorrhage occurred in a cavitary lesion while the patient was receiving radiation therapy 30 days after stopping sorafenib. Other adverse events included diarrhea, hand-foot syndrome, fatigue, and hypertension.

Dr. Gatzemeier said that a phase III trial has already started. It is to randomize 900 patients to a carboplatin/paclitaxel regimen with sorafenib or a placebo.

ZD6474

Dr. Ronald B. Natale reported that 83 patients achieved a median progression-free survival of 11 weeks on 300 mg per day of ZD6474. In comparison, only 8.1 weeks was reached by a control arm of 85 patients treated with 250 mg of gefitinib (Iressa) daily. The response rates were 8% and 1%, respectively.

The trial allowed patients who had progressed to cross over to the other agent. There were no additional responses, but 16 of 37 patients who switched from gefitinib to ZD6474 achieved more than 8 weeks' disease control vs. 7 of 29 patients who switched to gefitinib from ZD6474.

Overall survival, however, showed a trend in favor of starting on gefitinib: The median was 7.4 months vs. 6.1 months for those who began on ZD6474.

Adverse events included diarrhea, rash, asymptomatic QTc prolongation, and hypertension, but not hemoptysis.

Dr. Natale, a medical oncologist at the Cedars-Sinai Comprehensive Cancer Center in Los Angeles, concluded that the data support further investigation of ZD6474 as monotherapy.

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinic+al Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo. “Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

“When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinic+al Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo. “Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

“When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinic+al Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo. “Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

“When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

SAN DIEGO — Once-a-day step-down therapy can be an option for patients with mild, persistent asthma that has been stabilized by an inhaled corticosteroid, according to preliminary results from a 500-patient clinical trial presented at the international conference of the American Thoracic Society.

Dr. Stephen P. Peters said one puff a day of a fluticasone (100 mcg) and salmeterol (50 mcg) combination was as effective as 100 mcg of low-dose fluticasone twice a day. Only 20% of patients on either therapy failed treatment in the 15-week study.

A third group of patients did not fare as well on a pill containing 5 mg or 10 mg of montelukast each day. About 30% of patients failed treatment. Investigators calculated the relative risk of treatment failure as 60% higher than with fluticasone alone or fluticasone/salmeterol. Even so, the patients on montelukast fared well enough that all three regimens are viable, said Dr. Peters, director of research in pulmonary and critical care medicine at Wake Forest University, Winston-Salem, N.C.

“Although twice-a-day inhaled corticosteroid remains the treatment of choice for persistent asthma, alternatives could be considered on a case-by-case basis,” he said, citing the fluticasone/salmeterol combination. “There are still a lot of folks … who also did well, even on montelukast.”

The study, known as the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial, was sponsored by the American Lung Association's Asthma Clinical Research Centers. An unrestricted grant from GlaxoSmithKline provided financial support.

The trial randomized 168 patients to fluticasone, 162 patients to fluticasone/salmeterol, and 165 patients to montelukast after a phase-in period during which mild asthma was stabilized on an inhaled corticosteroid. Dr. Peters said all patients took a pill and used inhalers without knowing which one of their treatments had an active ingredient and which two were placebo.

The population was evenly divided between men and women and had an average age of 31 years. About 18% of patients were children, and more than a third were African American or Hispanic. As a group, they were longtime asthma patients with an average of 16 years since diagnosis. Dr. Peters characterized the participants as “the group we are used to seeing.”

The trial's primary outcome was time to treatment failure, which the investigators defined in seven ways, including physician judgment. Patients who had treatment failures could have more than one reason for a treatment failure.

There were 50 treatment failures with montelukast, 34 with fluticasone, and 33 with fluticasone/salmeterol. The most common reason was a 20% or greater drop in forced expiratory volume in 1 second (FEV₁), which 48% of patients with treatment failures experienced: 26 patients on montelukast, 16 on the combination, and 14 on single-agent fluticasone.

Three components of asthma exacerbation accounted for a total of 48% of treatment failures: systemic steroids, inhaled corticosteroid use (not counting exercise medication), and urgent care. The proportion of patients with asthma exacerbation was similar: 13% with montelukast, 11% with fluticasone/salmeterol, and 10% with fluticasone alone. The only significant difference was in inhaler use when montelukast was compared with fluticasone/salmeterol (23% vs. 17%).

In other measures, Dr. Peters said montelukast was “slightly inferior” for nocturnal awakenings, prebronchodilator FEV₁, and responses on the Asthma Control Questionnaire. Fluticasone/salmeterol was “slightly superior” for morning peak expiratory flow. He reported no difference in the Asthma Symptom Utility Index, Adult Asthma Quality of Life, serious adverse events, or percentage of symptom-free days (79% vs. 86%). For all three groups, most days were symptom free and rescue inhaler use was infrequent. Adherence is an underlying issue, he said in an interview.

SAN DIEGO — Once-a-day step-down therapy can be an option for patients with mild, persistent asthma that has been stabilized by an inhaled corticosteroid, according to preliminary results from a 500-patient clinical trial presented at the international conference of the American Thoracic Society.

Dr. Stephen P. Peters said one puff a day of a fluticasone (100 mcg) and salmeterol (50 mcg) combination was as effective as 100 mcg of low-dose fluticasone twice a day. Only 20% of patients on either therapy failed treatment in the 15-week study.

A third group of patients did not fare as well on a pill containing 5 mg or 10 mg of montelukast each day. About 30% of patients failed treatment. Investigators calculated the relative risk of treatment failure as 60% higher than with fluticasone alone or fluticasone/salmeterol. Even so, the patients on montelukast fared well enough that all three regimens are viable, said Dr. Peters, director of research in pulmonary and critical care medicine at Wake Forest University, Winston-Salem, N.C.

“Although twice-a-day inhaled corticosteroid remains the treatment of choice for persistent asthma, alternatives could be considered on a case-by-case basis,” he said, citing the fluticasone/salmeterol combination. “There are still a lot of folks … who also did well, even on montelukast.”

The study, known as the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial, was sponsored by the American Lung Association's Asthma Clinical Research Centers. An unrestricted grant from GlaxoSmithKline provided financial support.

The trial randomized 168 patients to fluticasone, 162 patients to fluticasone/salmeterol, and 165 patients to montelukast after a phase-in period during which mild asthma was stabilized on an inhaled corticosteroid. Dr. Peters said all patients took a pill and used inhalers without knowing which one of their treatments had an active ingredient and which two were placebo.

The population was evenly divided between men and women and had an average age of 31 years. About 18% of patients were children, and more than a third were African American or Hispanic. As a group, they were longtime asthma patients with an average of 16 years since diagnosis. Dr. Peters characterized the participants as “the group we are used to seeing.”

The trial's primary outcome was time to treatment failure, which the investigators defined in seven ways, including physician judgment. Patients who had treatment failures could have more than one reason for a treatment failure.

There were 50 treatment failures with montelukast, 34 with fluticasone, and 33 with fluticasone/salmeterol. The most common reason was a 20% or greater drop in forced expiratory volume in 1 second (FEV₁), which 48% of patients with treatment failures experienced: 26 patients on montelukast, 16 on the combination, and 14 on single-agent fluticasone.

Three components of asthma exacerbation accounted for a total of 48% of treatment failures: systemic steroids, inhaled corticosteroid use (not counting exercise medication), and urgent care. The proportion of patients with asthma exacerbation was similar: 13% with montelukast, 11% with fluticasone/salmeterol, and 10% with fluticasone alone. The only significant difference was in inhaler use when montelukast was compared with fluticasone/salmeterol (23% vs. 17%).

In other measures, Dr. Peters said montelukast was “slightly inferior” for nocturnal awakenings, prebronchodilator FEV₁, and responses on the Asthma Control Questionnaire. Fluticasone/salmeterol was “slightly superior” for morning peak expiratory flow. He reported no difference in the Asthma Symptom Utility Index, Adult Asthma Quality of Life, serious adverse events, or percentage of symptom-free days (79% vs. 86%). For all three groups, most days were symptom free and rescue inhaler use was infrequent. Adherence is an underlying issue, he said in an interview.

SAN DIEGO — Once-a-day step-down therapy can be an option for patients with mild, persistent asthma that has been stabilized by an inhaled corticosteroid, according to preliminary results from a 500-patient clinical trial presented at the international conference of the American Thoracic Society.

Dr. Stephen P. Peters said one puff a day of a fluticasone (100 mcg) and salmeterol (50 mcg) combination was as effective as 100 mcg of low-dose fluticasone twice a day. Only 20% of patients on either therapy failed treatment in the 15-week study.

A third group of patients did not fare as well on a pill containing 5 mg or 10 mg of montelukast each day. About 30% of patients failed treatment. Investigators calculated the relative risk of treatment failure as 60% higher than with fluticasone alone or fluticasone/salmeterol. Even so, the patients on montelukast fared well enough that all three regimens are viable, said Dr. Peters, director of research in pulmonary and critical care medicine at Wake Forest University, Winston-Salem, N.C.

“Although twice-a-day inhaled corticosteroid remains the treatment of choice for persistent asthma, alternatives could be considered on a case-by-case basis,” he said, citing the fluticasone/salmeterol combination. “There are still a lot of folks … who also did well, even on montelukast.”

The study, known as the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial, was sponsored by the American Lung Association's Asthma Clinical Research Centers. An unrestricted grant from GlaxoSmithKline provided financial support.

The trial randomized 168 patients to fluticasone, 162 patients to fluticasone/salmeterol, and 165 patients to montelukast after a phase-in period during which mild asthma was stabilized on an inhaled corticosteroid. Dr. Peters said all patients took a pill and used inhalers without knowing which one of their treatments had an active ingredient and which two were placebo.

The population was evenly divided between men and women and had an average age of 31 years. About 18% of patients were children, and more than a third were African American or Hispanic. As a group, they were longtime asthma patients with an average of 16 years since diagnosis. Dr. Peters characterized the participants as “the group we are used to seeing.”

The trial's primary outcome was time to treatment failure, which the investigators defined in seven ways, including physician judgment. Patients who had treatment failures could have more than one reason for a treatment failure.

There were 50 treatment failures with montelukast, 34 with fluticasone, and 33 with fluticasone/salmeterol. The most common reason was a 20% or greater drop in forced expiratory volume in 1 second (FEV₁), which 48% of patients with treatment failures experienced: 26 patients on montelukast, 16 on the combination, and 14 on single-agent fluticasone.

Three components of asthma exacerbation accounted for a total of 48% of treatment failures: systemic steroids, inhaled corticosteroid use (not counting exercise medication), and urgent care. The proportion of patients with asthma exacerbation was similar: 13% with montelukast, 11% with fluticasone/salmeterol, and 10% with fluticasone alone. The only significant difference was in inhaler use when montelukast was compared with fluticasone/salmeterol (23% vs. 17%).

In other measures, Dr. Peters said montelukast was “slightly inferior” for nocturnal awakenings, prebronchodilator FEV₁, and responses on the Asthma Control Questionnaire. Fluticasone/salmeterol was “slightly superior” for morning peak expiratory flow. He reported no difference in the Asthma Symptom Utility Index, Adult Asthma Quality of Life, serious adverse events, or percentage of symptom-free days (79% vs. 86%). For all three groups, most days were symptom free and rescue inhaler use was infrequent. Adherence is an underlying issue, he said in an interview.

ATLANTA — Only about half the people who screen positive for blood in the stool during routine physical examinations are thoroughly checked for colorectal cancer, according to a Centers for Disease Control and Prevention study presented at the annual meeting of the American Society of Clinical Oncology.

Complete colon examinations were reported by just 71 (53.1%) of 136 participants who said they had an abnormal fecal occult blood test (FOBT) that was not done because of a specific problem or as a follow-up to an earlier test.

Twenty-two people said they had no colon evaluation at all. Another 16 people reported that their doctors ordered a repeat of the FOBT. Eight had sigmoidoscopy, and three had a barium enema. Twelve patients went on to surgery, and four patients did not know what, if anything, was done as a result of their abnormal FOBT.

“The follow-up to screening seems to be a black box,” Dr. Lisa C. Richardson said in an interview at the poster session where she presented the data. Dr. Richardson, a medical officer in the CDC's Division of Cancer Prevention and Control, reviewed the responses of 4,908 people who participated in the 2000 National Health Interview Survey Cancer Control Supplement, a nationally representative sample of households. Eighty percent said they had the FOBT screen for colorectal cancer.

She and CDC coinvestigator Zahava Berkowitz determined that 287 respondents said they had an abnormal FOBT result. Of these, 151 were excluded from the sample because their tests were prompted by a specific problem or were done to follow-up on an earlier exam. The remaining 136 patients screened positive during routine FOBT. Analysis of demographic factors showed that people were more likely to receive a complete colon examination if they were older than 65, reported excellent or very good health status, or had a college education.

“Some doctors don't trust the fecal occult blood test results. They don't think a whole colon examination is necessary,” she said, calling for greater efforts to educate physicians and patients about the importance of total colon examination after an abnormal FOBT.

ATLANTA — Only about half the people who screen positive for blood in the stool during routine physical examinations are thoroughly checked for colorectal cancer, according to a Centers for Disease Control and Prevention study presented at the annual meeting of the American Society of Clinical Oncology.

Complete colon examinations were reported by just 71 (53.1%) of 136 participants who said they had an abnormal fecal occult blood test (FOBT) that was not done because of a specific problem or as a follow-up to an earlier test.

Twenty-two people said they had no colon evaluation at all. Another 16 people reported that their doctors ordered a repeat of the FOBT. Eight had sigmoidoscopy, and three had a barium enema. Twelve patients went on to surgery, and four patients did not know what, if anything, was done as a result of their abnormal FOBT.

“The follow-up to screening seems to be a black box,” Dr. Lisa C. Richardson said in an interview at the poster session where she presented the data. Dr. Richardson, a medical officer in the CDC's Division of Cancer Prevention and Control, reviewed the responses of 4,908 people who participated in the 2000 National Health Interview Survey Cancer Control Supplement, a nationally representative sample of households. Eighty percent said they had the FOBT screen for colorectal cancer.

She and CDC coinvestigator Zahava Berkowitz determined that 287 respondents said they had an abnormal FOBT result. Of these, 151 were excluded from the sample because their tests were prompted by a specific problem or were done to follow-up on an earlier exam. The remaining 136 patients screened positive during routine FOBT. Analysis of demographic factors showed that people were more likely to receive a complete colon examination if they were older than 65, reported excellent or very good health status, or had a college education.

“Some doctors don't trust the fecal occult blood test results. They don't think a whole colon examination is necessary,” she said, calling for greater efforts to educate physicians and patients about the importance of total colon examination after an abnormal FOBT.

ATLANTA — Only about half the people who screen positive for blood in the stool during routine physical examinations are thoroughly checked for colorectal cancer, according to a Centers for Disease Control and Prevention study presented at the annual meeting of the American Society of Clinical Oncology.

Complete colon examinations were reported by just 71 (53.1%) of 136 participants who said they had an abnormal fecal occult blood test (FOBT) that was not done because of a specific problem or as a follow-up to an earlier test.

Twenty-two people said they had no colon evaluation at all. Another 16 people reported that their doctors ordered a repeat of the FOBT. Eight had sigmoidoscopy, and three had a barium enema. Twelve patients went on to surgery, and four patients did not know what, if anything, was done as a result of their abnormal FOBT.

“The follow-up to screening seems to be a black box,” Dr. Lisa C. Richardson said in an interview at the poster session where she presented the data. Dr. Richardson, a medical officer in the CDC's Division of Cancer Prevention and Control, reviewed the responses of 4,908 people who participated in the 2000 National Health Interview Survey Cancer Control Supplement, a nationally representative sample of households. Eighty percent said they had the FOBT screen for colorectal cancer.

She and CDC coinvestigator Zahava Berkowitz determined that 287 respondents said they had an abnormal FOBT result. Of these, 151 were excluded from the sample because their tests were prompted by a specific problem or were done to follow-up on an earlier exam. The remaining 136 patients screened positive during routine FOBT. Analysis of demographic factors showed that people were more likely to receive a complete colon examination if they were older than 65, reported excellent or very good health status, or had a college education.

“Some doctors don't trust the fecal occult blood test results. They don't think a whole colon examination is necessary,” she said, calling for greater efforts to educate physicians and patients about the importance of total colon examination after an abnormal FOBT.

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was 3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of 3.7% and 3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population,” he added.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to affect lumbar spine BMD as much. The reductions were 3.4% for 52 women deficient in vitamin D who completed the study on exemestane and 2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was 3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of 3.7% and 3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population,” he added.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to affect lumbar spine BMD as much. The reductions were 3.4% for 52 women deficient in vitamin D who completed the study on exemestane and 2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was 3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of 3.7% and 3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population,” he added.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to affect lumbar spine BMD as much. The reductions were 3.4% for 52 women deficient in vitamin D who completed the study on exemestane and 2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said.

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said. “When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

'Low vitamin D status could be one of the factors predisposing patients to breast cancer.' DR. LØNNING

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said. “When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

'Low vitamin D status could be one of the factors predisposing patients to breast cancer.' DR. LØNNING

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said. “When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

'Low vitamin D status could be one of the factors predisposing patients to breast cancer.' DR. LØNNING

SAN FRANCISCO — Physicians can administer the live attenuated influenza vaccine marketed as FluMist during the same healthy infant visit in which they administer the measles-mumps-rubella and varicella vaccines, without diminishing the safety or effectiveness of any of the vaccines, according to the results of a phase III trial reported at the annual meeting of the Pediatric Academic Societies.

“There's no interference with the antibody response to the other vaccines given at the same time,” Dr. Terry Nolan said in an interview alongside a poster describing outcomes for 1,245 infants aged 12–15 months in the prospective, placebo-controlled trial.

The study randomized healthy infants at 44 sites in the United States during the months from May to October in 2001 and 2002. Infants also were randomized from November to May in 2001 and 2002 at three additional sites in Australia, where Dr. Nolan is the head of the school of population health at the University of Melbourne.

Investigators used the formulation of FluMist that is currently approved for healthy children and adults aged 5–49 years in the United States. MedImmune Vaccines Inc. of Gaithersburg, Md., manufacturer of FluMist, has announced that it will seek approval of a newer formulation in children as young as 6 months.

The principal change in the new product is that it can be refrigerated—the current formulation must be stored in a freezer—and delivered in a lower dose. MedImmune sponsored Dr. Nolan's trial.

Both FluMist formulations are delivered as an intranasal spray. This gives FluMist an advantage over the trivalent inactivated influenza (TIV) vaccine that is already approved for inoculation of healthy infants, according to Dr. Nolan.

“The vaccine [FluMist] is easier to give to babies because it is not an injection. They don't cry. They love it,” he said. “And it appears to be as effective, if not more effective, than the injected vaccine. So it's a very promising vaccine for the future.”

Dr. Nolan's study randomized infants into three groups:

▸ In Group 1, 411 infants received the measles-mumps-rubella (MMR II) and varicella (Varivax) vaccines and a placebo on the first visit. They were given FluMist on the second and third visits.

▸ In Group 2, 422 infants received MMR-II, Varivax, and FluMist on their first visit. They were given FluMist on the second visit, and a placebo on the third visit.

▸ In Group 3, the remaining 412 infants received FluMist alone during the first and second visits. They were given MMR II and Varivax on the third visit.

Investigators collected serum samples during office visits on days 0, 42, and 72 of the study. They reported that concurrent administration of FluMist with the other vaccines did not alter seroresponse rates or geometric mean titers to MMR II and Varivax vaccines. Similarly, there was no change in the strain-specific seroconversion rates or geometric mean titers for each of the three vaccine strains in the FluMist vaccine.

A comparison of the first and second groups showed that children in Group 2 who were given concurrent vaccinations had significantly more rhinorrhea and nasal congestion during the following 42 days than did those in Group 1 (84% vs. 78%, respectively). Differences in other reactogenicity events were not statistically significant at 42 days.

During the 10 days after the first dose of FluMist, however, children in Group 2 who were given concomitant vaccinations had significantly more irritability (60% vs. 52%), fever over 101° F (29% vs. 14%), and vomiting (14% vs. 9%) than did children in Group 3 who received FluMist alone.

The most frequently reported adverse events after concurrent vaccination (Group 2) were diarrhea (17%) and otitis media (8%). Nine serious adverse events (including pneumonia, bronchiolitis, croup, viral chest infection and/or bronchospasm) may have been related to the study vaccine.

The investigators concluded that concurrent administration was safe and well tolerated.

The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

SAN FRANCISCO — Physicians can administer the live attenuated influenza vaccine marketed as FluMist during the same healthy infant visit in which they administer the measles-mumps-rubella and varicella vaccines, without diminishing the safety or effectiveness of any of the vaccines, according to the results of a phase III trial reported at the annual meeting of the Pediatric Academic Societies.

“There's no interference with the antibody response to the other vaccines given at the same time,” Dr. Terry Nolan said in an interview alongside a poster describing outcomes for 1,245 infants aged 12–15 months in the prospective, placebo-controlled trial.

The study randomized healthy infants at 44 sites in the United States during the months from May to October in 2001 and 2002. Infants also were randomized from November to May in 2001 and 2002 at three additional sites in Australia, where Dr. Nolan is the head of the school of population health at the University of Melbourne.

Investigators used the formulation of FluMist that is currently approved for healthy children and adults aged 5–49 years in the United States. MedImmune Vaccines Inc. of Gaithersburg, Md., manufacturer of FluMist, has announced that it will seek approval of a newer formulation in children as young as 6 months.

The principal change in the new product is that it can be refrigerated—the current formulation must be stored in a freezer—and delivered in a lower dose. MedImmune sponsored Dr. Nolan's trial.

Both FluMist formulations are delivered as an intranasal spray. This gives FluMist an advantage over the trivalent inactivated influenza (TIV) vaccine that is already approved for inoculation of healthy infants, according to Dr. Nolan.

“The vaccine [FluMist] is easier to give to babies because it is not an injection. They don't cry. They love it,” he said. “And it appears to be as effective, if not more effective, than the injected vaccine. So it's a very promising vaccine for the future.”

Dr. Nolan's study randomized infants into three groups:

▸ In Group 1, 411 infants received the measles-mumps-rubella (MMR II) and varicella (Varivax) vaccines and a placebo on the first visit. They were given FluMist on the second and third visits.

▸ In Group 2, 422 infants received MMR-II, Varivax, and FluMist on their first visit. They were given FluMist on the second visit, and a placebo on the third visit.

▸ In Group 3, the remaining 412 infants received FluMist alone during the first and second visits. They were given MMR II and Varivax on the third visit.

Investigators collected serum samples during office visits on days 0, 42, and 72 of the study. They reported that concurrent administration of FluMist with the other vaccines did not alter seroresponse rates or geometric mean titers to MMR II and Varivax vaccines. Similarly, there was no change in the strain-specific seroconversion rates or geometric mean titers for each of the three vaccine strains in the FluMist vaccine.

A comparison of the first and second groups showed that children in Group 2 who were given concurrent vaccinations had significantly more rhinorrhea and nasal congestion during the following 42 days than did those in Group 1 (84% vs. 78%, respectively). Differences in other reactogenicity events were not statistically significant at 42 days.

During the 10 days after the first dose of FluMist, however, children in Group 2 who were given concomitant vaccinations had significantly more irritability (60% vs. 52%), fever over 101° F (29% vs. 14%), and vomiting (14% vs. 9%) than did children in Group 3 who received FluMist alone.

The most frequently reported adverse events after concurrent vaccination (Group 2) were diarrhea (17%) and otitis media (8%). Nine serious adverse events (including pneumonia, bronchiolitis, croup, viral chest infection and/or bronchospasm) may have been related to the study vaccine.

The investigators concluded that concurrent administration was safe and well tolerated.

The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

SAN FRANCISCO — Physicians can administer the live attenuated influenza vaccine marketed as FluMist during the same healthy infant visit in which they administer the measles-mumps-rubella and varicella vaccines, without diminishing the safety or effectiveness of any of the vaccines, according to the results of a phase III trial reported at the annual meeting of the Pediatric Academic Societies.

“There's no interference with the antibody response to the other vaccines given at the same time,” Dr. Terry Nolan said in an interview alongside a poster describing outcomes for 1,245 infants aged 12–15 months in the prospective, placebo-controlled trial.

The study randomized healthy infants at 44 sites in the United States during the months from May to October in 2001 and 2002. Infants also were randomized from November to May in 2001 and 2002 at three additional sites in Australia, where Dr. Nolan is the head of the school of population health at the University of Melbourne.

Investigators used the formulation of FluMist that is currently approved for healthy children and adults aged 5–49 years in the United States. MedImmune Vaccines Inc. of Gaithersburg, Md., manufacturer of FluMist, has announced that it will seek approval of a newer formulation in children as young as 6 months.

The principal change in the new product is that it can be refrigerated—the current formulation must be stored in a freezer—and delivered in a lower dose. MedImmune sponsored Dr. Nolan's trial.

Both FluMist formulations are delivered as an intranasal spray. This gives FluMist an advantage over the trivalent inactivated influenza (TIV) vaccine that is already approved for inoculation of healthy infants, according to Dr. Nolan.

“The vaccine [FluMist] is easier to give to babies because it is not an injection. They don't cry. They love it,” he said. “And it appears to be as effective, if not more effective, than the injected vaccine. So it's a very promising vaccine for the future.”

Dr. Nolan's study randomized infants into three groups:

▸ In Group 1, 411 infants received the measles-mumps-rubella (MMR II) and varicella (Varivax) vaccines and a placebo on the first visit. They were given FluMist on the second and third visits.

▸ In Group 2, 422 infants received MMR-II, Varivax, and FluMist on their first visit. They were given FluMist on the second visit, and a placebo on the third visit.

▸ In Group 3, the remaining 412 infants received FluMist alone during the first and second visits. They were given MMR II and Varivax on the third visit.

Investigators collected serum samples during office visits on days 0, 42, and 72 of the study. They reported that concurrent administration of FluMist with the other vaccines did not alter seroresponse rates or geometric mean titers to MMR II and Varivax vaccines. Similarly, there was no change in the strain-specific seroconversion rates or geometric mean titers for each of the three vaccine strains in the FluMist vaccine.

A comparison of the first and second groups showed that children in Group 2 who were given concurrent vaccinations had significantly more rhinorrhea and nasal congestion during the following 42 days than did those in Group 1 (84% vs. 78%, respectively). Differences in other reactogenicity events were not statistically significant at 42 days.

During the 10 days after the first dose of FluMist, however, children in Group 2 who were given concomitant vaccinations had significantly more irritability (60% vs. 52%), fever over 101° F (29% vs. 14%), and vomiting (14% vs. 9%) than did children in Group 3 who received FluMist alone.

The most frequently reported adverse events after concurrent vaccination (Group 2) were diarrhea (17%) and otitis media (8%). Nine serious adverse events (including pneumonia, bronchiolitis, croup, viral chest infection and/or bronchospasm) may have been related to the study vaccine.

The investigators concluded that concurrent administration was safe and well tolerated.

The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.