Nephrology

Everolimus, a kinase inhibitor already approved for treating kidney cancer, has been approved as a treatment for slowly growing, benign tumors in patients with tuberous sclerosis, the Food and Drug Administration announced on Nov. 1.

Everolimus, marketed as Afinitor for kidney cancer, was approved for treating subependymal giant cell astrocytoma (SEGA) associated with the rare genetic disorder, in cases in which these tumors cannot be treated surgically. (Everolimus is also approved for prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant and is marketed as Zortress for this indication.) It will be marketed as Afinitor for the SEGA indication and will be available in a tablet formulation.

"Patients with this disease currently have limited treatment options beyond surgical intervention," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the Center for Drug Evaluation and Research, said in an FDA statement announcing the approval. "It is important for research to continue in rare diseases where patients have few or no existing drug treatment options." About 6%-9% of patients with tuberous sclerosis have SEGAs, which are potentially fatal, slow-growing tumors.

The accelerated approval was based on a study of 28 patients with SEGAs, which found that after 6 months of treatment, 9 patients (32%) had more than a 50% reduction in the volume of their largest SEGA tumor, which included several patients whose tumors had recurred after surgery. The duration of response in these patients ranged from about 3 months to 2½ years (median 266 days). Of the nine patients, seven still had a 50% reduction in tumor volume at the last follow-up, according to the FDA.

In addition, none of the patients in the study developed any new tumors, although none of the tumors completely resolved.

The most common adverse events reported by patients in patients treated for SEGA included upper respiratory tract infections, sinus and ear infections, mouth sores, and fever. Laboratory test abnormalities associated with treatment included liver enzyme elevations, hyperlipidemia, high blood sugar, and decreases in white blood cells, red blood cells, and platelets.

Everolimus was approved in 2009 for the kidney cancer indication, in patients who failed treatment with sunitinib (Sutent) or sorafenib (Nexavar).

Everolimus, a kinase inhibitor already approved for treating kidney cancer, has been approved as a treatment for slowly growing, benign tumors in patients with tuberous sclerosis, the Food and Drug Administration announced on Nov. 1.

Everolimus, marketed as Afinitor for kidney cancer, was approved for treating subependymal giant cell astrocytoma (SEGA) associated with the rare genetic disorder, in cases in which these tumors cannot be treated surgically. (Everolimus is also approved for prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant and is marketed as Zortress for this indication.) It will be marketed as Afinitor for the SEGA indication and will be available in a tablet formulation.

"Patients with this disease currently have limited treatment options beyond surgical intervention," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the Center for Drug Evaluation and Research, said in an FDA statement announcing the approval. "It is important for research to continue in rare diseases where patients have few or no existing drug treatment options." About 6%-9% of patients with tuberous sclerosis have SEGAs, which are potentially fatal, slow-growing tumors.

The accelerated approval was based on a study of 28 patients with SEGAs, which found that after 6 months of treatment, 9 patients (32%) had more than a 50% reduction in the volume of their largest SEGA tumor, which included several patients whose tumors had recurred after surgery. The duration of response in these patients ranged from about 3 months to 2½ years (median 266 days). Of the nine patients, seven still had a 50% reduction in tumor volume at the last follow-up, according to the FDA.

In addition, none of the patients in the study developed any new tumors, although none of the tumors completely resolved.

The most common adverse events reported by patients in patients treated for SEGA included upper respiratory tract infections, sinus and ear infections, mouth sores, and fever. Laboratory test abnormalities associated with treatment included liver enzyme elevations, hyperlipidemia, high blood sugar, and decreases in white blood cells, red blood cells, and platelets.

Everolimus was approved in 2009 for the kidney cancer indication, in patients who failed treatment with sunitinib (Sutent) or sorafenib (Nexavar).

Everolimus, a kinase inhibitor already approved for treating kidney cancer, has been approved as a treatment for slowly growing, benign tumors in patients with tuberous sclerosis, the Food and Drug Administration announced on Nov. 1.

Everolimus, marketed as Afinitor for kidney cancer, was approved for treating subependymal giant cell astrocytoma (SEGA) associated with the rare genetic disorder, in cases in which these tumors cannot be treated surgically. (Everolimus is also approved for prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant and is marketed as Zortress for this indication.) It will be marketed as Afinitor for the SEGA indication and will be available in a tablet formulation.

"Patients with this disease currently have limited treatment options beyond surgical intervention," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the Center for Drug Evaluation and Research, said in an FDA statement announcing the approval. "It is important for research to continue in rare diseases where patients have few or no existing drug treatment options." About 6%-9% of patients with tuberous sclerosis have SEGAs, which are potentially fatal, slow-growing tumors.

The accelerated approval was based on a study of 28 patients with SEGAs, which found that after 6 months of treatment, 9 patients (32%) had more than a 50% reduction in the volume of their largest SEGA tumor, which included several patients whose tumors had recurred after surgery. The duration of response in these patients ranged from about 3 months to 2½ years (median 266 days). Of the nine patients, seven still had a 50% reduction in tumor volume at the last follow-up, according to the FDA.

In addition, none of the patients in the study developed any new tumors, although none of the tumors completely resolved.

The most common adverse events reported by patients in patients treated for SEGA included upper respiratory tract infections, sinus and ear infections, mouth sores, and fever. Laboratory test abnormalities associated with treatment included liver enzyme elevations, hyperlipidemia, high blood sugar, and decreases in white blood cells, red blood cells, and platelets.

Everolimus was approved in 2009 for the kidney cancer indication, in patients who failed treatment with sunitinib (Sutent) or sorafenib (Nexavar).

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

Aspirin could cut the risk of dying of prostate cancer by almost 50% for men diagnosed with localized disease, a study has shown.

The investigators also found that other anticoagulants decreased the risk of prostate cancer–specific death in these men, but aspirin seemed to have the biggest positive effect, Dr. Kevin Choe said at a press briefing, held in advance of the annual meeting of the American Society for Radiation Oncology.

“Evidence has shown that anticoagulants may interfere with cancer growth and spread,” said Dr. Choe, a radiation oncologist at the University of Texas at Dallas. “If the major effect of anticoagulants is preventing metastasis, this may be why previous clinical trials with anticoagulation medications produced mixed results, since most patients in these trials already had metastasis. If the cancer had already metastasized, then anticoagulants may not be as beneficial.”

Dr. Choe and his colleagues based their retrospective study on data extracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). They used the database to investigate the effect of anticoagulation medications, including aspirin, warfarin, clopidogrel, and enoxaparin, on the risk of dying of prostate cancer that has not spread.

The study group comprised 5,295 men with localized adenocarcinoma of the prostate. Patients were treated with radical prostatectomy (3,523) or radiotherapy (1,772). Of the entire group, 1,932 men (37%) were using at least one anticoagulant at the time of their diagnosis or during follow-up (warfarin 428, clopidogrel 287, enoxaparin 26, aspirin 1,649). Almost a third of the men (28%) were taking androgen deprivation therapy.

The patients’ mean age was 65 years, and the mean prostate-specific antigen, 6 ng/mL. Based on the National Comprehensive Cancer Network risk stratification, 41% of the patients had low-risk disease, 37% intermediate risk, and 22% high risk.

Men who were not taking any anticoagulants were significantly younger than those taking the drugs (64 vs. 66 years), and more likely to have undergone radiotherapy (69% vs. 62%). The PSA was slightly, but not significantly, lower in the anticoagulant group, but the Gleason score and T stages were similar.

The median follow-up time was 59 months. At 7 and 10 years, prostate cancer–specific mortality was significantly lower in the anticoagulant group (1% vs. 4% and 4% vs. 10%, respectively; P less than .01).

The investigators also performed a subgroup analysis to determine the survival advantage associated with each risk category and with each type of anticoagulant. The survival benefit was greatest in patients with high-risk disease (2% vs. 8% mortality at 7 years and 4% vs. 22% at 10 years; P = less than .01). The benefit was seen whether the men had received radiation or hormone therapy.

A multivariate analysis found that the use of any anticoagulant was an independent predictor of prostate cancer–specific survival, reducing the risk of death by 47% (hazard ratio, 0.53; P less than .01). A medication analysis suggested that aspirin conferred most of the survival benefit.

Because the database didn’t contain much information on the duration of anticoagulant treatment, Dr. Choe couldn’t draw any conclusion about an association between length of treatment and risk of metastasis and death. Nor, he said, could he recommend that men without prostate cancer take aspirin as a prostate cancer preventative, or that men with newly diagnosed prostate cancer begin taking it.

“There are risks associated with anticoagulants, and in fact they can increase the risk of bleeding from the rectal wall during prostate cancer treatment,” he said. “Further studies are necessary before the addition of aspirin to prostate cancer therapy could become a standard treatment.”

However, he added, “for those who are already taking an anticoagulant for some other reason, we might expect to see an additional benefit in prostate cancer.”

The mechanistic relationship between metastatic disease and anticoagulants remains unclear, Dr. Choe said. However, in vitro and in vivo experiments suggest that normal platelet aggregation may protect circulating tumor cells. “Once the cells break away from the original site into the bloodstream, they are coated by platelets that prevent immune cells from attacking and seem to aid the tumor cells in sticking somewhere and beginning to grow,” Dr. Choe said. “Any interference with this clotting function might decrease the protective effect of platelets.”

Neither Dr. Choe nor his coinvestigators reported any relevant financial conflicts.

LONG BEACH, Calif. – Among women who underwent midurethral sling surgery for stress incontinence, failure at 12 months was twice as likely if they also had urge incontinence symptoms at baseline, a study has shown.

In a multivariate analysis of 12-month outcomes of the Trial of Mid-Urethral Slings (TOMUS), Dr. Holly E. Richter determined that the risk of treatment failure increased by 94% for every 10-point increase in the MESA (Medical, Epidemiologic, and Social Aspects of Aging) urge score.

Three other baseline factors also emerged as significant independent predictors of treatment failure. Women who had prior urinary incontinence surgery were 96% more likely to experience treatment failure. Those with decreased urethral motility, as judged by a maximum Q-tip excursion angle of less than 30 degrees were 89% more likely to fail. And every 10-g increase in pad weight increased the risk of treatment failure by 6%. The results were adjusted for treatment site and treatment group.

At the annual meeting of the American Urogynecologic Society, Dr. Richter of the University of Alabama at Birmingham pointed out that TOMUS and the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) yielded similar results in predicting treatment failure.

“There is one covariate to me that really stands out,” she said at the meeting. “We’ve spent millions of dollars, two big trials, almost 1,200 patients, and I think if we learned one thing, [it’s that] urge incontinence symptoms are problematic. I think that in studies we do in the future regarding women [who] undergo stress incontinence surgery, we need to take a more robust look at this.”

In the TOMUS study, investigators randomized 597 women to receive a transobturator or retropubic midurethral sling. All patients suffered from stress-predominant urinary incontinence.

Twelve months following the surgery, investigators were able to evaluate 563 of the women for objective and subjective cure. Objective cure consisted of a negative stress test, a negative 24-hour pad test, and no behavioral, pharmacologic, or surgical retreatment for stress urinary incontinence (SUI). Subjective cure consisted of no self-reported symptoms of SUI, no self-reported leakage on a 3-day voiding diary, and no retreatment for SUI.

Of the 563 women examined at 12 months, 54% met all the criteria for objective and subjective cure. Of the remaining 46% of women, 42% had both objective and subjective failure, 50% had subjective failure only, and 6% had objective failure only. (No objective failure data were available for the remaining 2% of women in that group).

There were no significant differences between the retropubic and midurethral sling groups in the relationships between each covariate and treatment failure.

Several factors emerged as significant independent predictors of objective versus subjective failure. They included no concomitant surgery (odds ratio, 2.22); increased age (OR, 1.46 per 10 years); increased bother (OR, 1.10 for every 10 points in Urinary Distress Inventory scores); and pad weight (OR, 1.08 for every 10 g).

“This information may assist in counseling women regarding efficacy and setting appropriate expectations for women at increased risk for failure,” Dr. Richter said.

He disclosed receiving research support from Pfizer Inc. and serving as a consultant for Astellas Pharma Inc., Xanodyne Pharmaceuticals Inc., and IDEO. The TOMUS study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

LONG BEACH, Calif. – Among women who underwent midurethral sling surgery for stress incontinence, failure at 12 months was twice as likely if they also had urge incontinence symptoms at baseline, a study has shown.

In a multivariate analysis of 12-month outcomes of the Trial of Mid-Urethral Slings (TOMUS), Dr. Holly E. Richter determined that the risk of treatment failure increased by 94% for every 10-point increase in the MESA (Medical, Epidemiologic, and Social Aspects of Aging) urge score.

Three other baseline factors also emerged as significant independent predictors of treatment failure. Women who had prior urinary incontinence surgery were 96% more likely to experience treatment failure. Those with decreased urethral motility, as judged by a maximum Q-tip excursion angle of less than 30 degrees were 89% more likely to fail. And every 10-g increase in pad weight increased the risk of treatment failure by 6%. The results were adjusted for treatment site and treatment group.

At the annual meeting of the American Urogynecologic Society, Dr. Richter of the University of Alabama at Birmingham pointed out that TOMUS and the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) yielded similar results in predicting treatment failure.

“There is one covariate to me that really stands out,” she said at the meeting. “We’ve spent millions of dollars, two big trials, almost 1,200 patients, and I think if we learned one thing, [it’s that] urge incontinence symptoms are problematic. I think that in studies we do in the future regarding women [who] undergo stress incontinence surgery, we need to take a more robust look at this.”

In the TOMUS study, investigators randomized 597 women to receive a transobturator or retropubic midurethral sling. All patients suffered from stress-predominant urinary incontinence.

Twelve months following the surgery, investigators were able to evaluate 563 of the women for objective and subjective cure. Objective cure consisted of a negative stress test, a negative 24-hour pad test, and no behavioral, pharmacologic, or surgical retreatment for stress urinary incontinence (SUI). Subjective cure consisted of no self-reported symptoms of SUI, no self-reported leakage on a 3-day voiding diary, and no retreatment for SUI.

Of the 563 women examined at 12 months, 54% met all the criteria for objective and subjective cure. Of the remaining 46% of women, 42% had both objective and subjective failure, 50% had subjective failure only, and 6% had objective failure only. (No objective failure data were available for the remaining 2% of women in that group).

There were no significant differences between the retropubic and midurethral sling groups in the relationships between each covariate and treatment failure.

Several factors emerged as significant independent predictors of objective versus subjective failure. They included no concomitant surgery (odds ratio, 2.22); increased age (OR, 1.46 per 10 years); increased bother (OR, 1.10 for every 10 points in Urinary Distress Inventory scores); and pad weight (OR, 1.08 for every 10 g).

“This information may assist in counseling women regarding efficacy and setting appropriate expectations for women at increased risk for failure,” Dr. Richter said.

He disclosed receiving research support from Pfizer Inc. and serving as a consultant for Astellas Pharma Inc., Xanodyne Pharmaceuticals Inc., and IDEO. The TOMUS study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

LONG BEACH, Calif. – Among women who underwent midurethral sling surgery for stress incontinence, failure at 12 months was twice as likely if they also had urge incontinence symptoms at baseline, a study has shown.

In a multivariate analysis of 12-month outcomes of the Trial of Mid-Urethral Slings (TOMUS), Dr. Holly E. Richter determined that the risk of treatment failure increased by 94% for every 10-point increase in the MESA (Medical, Epidemiologic, and Social Aspects of Aging) urge score.

Three other baseline factors also emerged as significant independent predictors of treatment failure. Women who had prior urinary incontinence surgery were 96% more likely to experience treatment failure. Those with decreased urethral motility, as judged by a maximum Q-tip excursion angle of less than 30 degrees were 89% more likely to fail. And every 10-g increase in pad weight increased the risk of treatment failure by 6%. The results were adjusted for treatment site and treatment group.

At the annual meeting of the American Urogynecologic Society, Dr. Richter of the University of Alabama at Birmingham pointed out that TOMUS and the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) yielded similar results in predicting treatment failure.

“There is one covariate to me that really stands out,” she said at the meeting. “We’ve spent millions of dollars, two big trials, almost 1,200 patients, and I think if we learned one thing, [it’s that] urge incontinence symptoms are problematic. I think that in studies we do in the future regarding women [who] undergo stress incontinence surgery, we need to take a more robust look at this.”

In the TOMUS study, investigators randomized 597 women to receive a transobturator or retropubic midurethral sling. All patients suffered from stress-predominant urinary incontinence.

Twelve months following the surgery, investigators were able to evaluate 563 of the women for objective and subjective cure. Objective cure consisted of a negative stress test, a negative 24-hour pad test, and no behavioral, pharmacologic, or surgical retreatment for stress urinary incontinence (SUI). Subjective cure consisted of no self-reported symptoms of SUI, no self-reported leakage on a 3-day voiding diary, and no retreatment for SUI.

Of the 563 women examined at 12 months, 54% met all the criteria for objective and subjective cure. Of the remaining 46% of women, 42% had both objective and subjective failure, 50% had subjective failure only, and 6% had objective failure only. (No objective failure data were available for the remaining 2% of women in that group).

There were no significant differences between the retropubic and midurethral sling groups in the relationships between each covariate and treatment failure.

Several factors emerged as significant independent predictors of objective versus subjective failure. They included no concomitant surgery (odds ratio, 2.22); increased age (OR, 1.46 per 10 years); increased bother (OR, 1.10 for every 10 points in Urinary Distress Inventory scores); and pad weight (OR, 1.08 for every 10 g).

“This information may assist in counseling women regarding efficacy and setting appropriate expectations for women at increased risk for failure,” Dr. Richter said.

He disclosed receiving research support from Pfizer Inc. and serving as a consultant for Astellas Pharma Inc., Xanodyne Pharmaceuticals Inc., and IDEO. The TOMUS study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases.

MILAN – Tivozanib, an investigational agent, is not only active in the treatment of renal cell carcinoma, but is also associated with minimal “off target” toxicity, according to phase II study findings.

The tyrosine kinase inhibitor (TKI), which targets all three vascular epithelial growth factor (VEGF) receptors, was associated with an overall median progression-free survival of 11.8 months in a difficult-to-treat patient population; 17% of 272 patients had nonclear cell histology, 27% did not have prior nephrectomy, and 46% had received at least one prior treatment.

Median progression-free survival was slightly longer, at 14.8 months, in patients with clear cell histology who had also undergone nephrectomy, which is the population of patients that is most commonly studied to gain drug approval in renal cell carcinoma.

“Patients randomized to continue tivozanib had a significantly higher disease control rate and median progression-free survival compared with those randomized to placebo,” said Dr. Dimitry Nosov of the N.N. Blokhin Russian Cancer Research Center in Moscow, who presented preliminary results of the randomized discontinuation trial at the annual congress of the European Society for Medical Oncology.

The trial involved a 16-week, open-label phase during which all patients received treatment with tivozanib, at a dosage of 1.5 mg/day for 3 weeks of a 4-week cycle. In all, 76 patients with progressive disease then stopped treatment, 78 of those with partial or complete responses continued open-label treatment, and 111 patients with stable disease were randomized to receive tivozanib or placebo for a further 12 weeks.

Dr. Nosov noted that the percentage of patients who remained progression free at 12 weeks following randomization to either tivozanib or placebo doubled with the active treatment (48% vs. 21%; P = .003).

The drug is reported to have greater potency for VEGF receptors 1, 2, and 3 than do other available agents, including Pfizer Inc.’s investigational agent axitinib, which may account for its low rate of “off-target” adverse events such as mucositis, stomatitis, fatigue, neutropenia, and hand-foot syndrome as seen in the trial. The most common side effects (all grades) reported for at least 10% of patients were hypertension (50%), dysphonia (22%), asthenia (approximately 13%), and diarrhea (12%).

“What’s extremely encouraging is the very good tolerability of this agent,” Dr. Tim Eisen, a professor at the University of Cambridge (England).

Dr. Eisen noted that although the number of patients who discontinued treatment was high at the end of the open-label treatment phase, it was also encouraging that progression-free survival was almost as good in patients who had stable disease and continued treatment with tivozanib as it was in those who had achieved a partial or complete response and received continued open-label treatment. “This might influence how we use the agent,” in clinical practice, he suggested.

The study was sponsored by AVEO Pharmaceuticals Inc. Dr. Nosov had no potential conflicts of interest, but several of his coauthors were employees of AVEO. The discussant, Dr. Eisen, has acted in advisory capacity for AVEO and GlaxoSmithKline, and has received research support and acted as an advisor to Bayer, Pfizer, and Roche.

MILAN – Tivozanib, an investigational agent, is not only active in the treatment of renal cell carcinoma, but is also associated with minimal “off target” toxicity, according to phase II study findings.

The tyrosine kinase inhibitor (TKI), which targets all three vascular epithelial growth factor (VEGF) receptors, was associated with an overall median progression-free survival of 11.8 months in a difficult-to-treat patient population; 17% of 272 patients had nonclear cell histology, 27% did not have prior nephrectomy, and 46% had received at least one prior treatment.

Median progression-free survival was slightly longer, at 14.8 months, in patients with clear cell histology who had also undergone nephrectomy, which is the population of patients that is most commonly studied to gain drug approval in renal cell carcinoma.

“Patients randomized to continue tivozanib had a significantly higher disease control rate and median progression-free survival compared with those randomized to placebo,” said Dr. Dimitry Nosov of the N.N. Blokhin Russian Cancer Research Center in Moscow, who presented preliminary results of the randomized discontinuation trial at the annual congress of the European Society for Medical Oncology.

The trial involved a 16-week, open-label phase during which all patients received treatment with tivozanib, at a dosage of 1.5 mg/day for 3 weeks of a 4-week cycle. In all, 76 patients with progressive disease then stopped treatment, 78 of those with partial or complete responses continued open-label treatment, and 111 patients with stable disease were randomized to receive tivozanib or placebo for a further 12 weeks.

Dr. Nosov noted that the percentage of patients who remained progression free at 12 weeks following randomization to either tivozanib or placebo doubled with the active treatment (48% vs. 21%; P = .003).

The drug is reported to have greater potency for VEGF receptors 1, 2, and 3 than do other available agents, including Pfizer Inc.’s investigational agent axitinib, which may account for its low rate of “off-target” adverse events such as mucositis, stomatitis, fatigue, neutropenia, and hand-foot syndrome as seen in the trial. The most common side effects (all grades) reported for at least 10% of patients were hypertension (50%), dysphonia (22%), asthenia (approximately 13%), and diarrhea (12%).

“What’s extremely encouraging is the very good tolerability of this agent,” Dr. Tim Eisen, a professor at the University of Cambridge (England).

Dr. Eisen noted that although the number of patients who discontinued treatment was high at the end of the open-label treatment phase, it was also encouraging that progression-free survival was almost as good in patients who had stable disease and continued treatment with tivozanib as it was in those who had achieved a partial or complete response and received continued open-label treatment. “This might influence how we use the agent,” in clinical practice, he suggested.

The study was sponsored by AVEO Pharmaceuticals Inc. Dr. Nosov had no potential conflicts of interest, but several of his coauthors were employees of AVEO. The discussant, Dr. Eisen, has acted in advisory capacity for AVEO and GlaxoSmithKline, and has received research support and acted as an advisor to Bayer, Pfizer, and Roche.

MILAN – Tivozanib, an investigational agent, is not only active in the treatment of renal cell carcinoma, but is also associated with minimal “off target” toxicity, according to phase II study findings.

The tyrosine kinase inhibitor (TKI), which targets all three vascular epithelial growth factor (VEGF) receptors, was associated with an overall median progression-free survival of 11.8 months in a difficult-to-treat patient population; 17% of 272 patients had nonclear cell histology, 27% did not have prior nephrectomy, and 46% had received at least one prior treatment.

Median progression-free survival was slightly longer, at 14.8 months, in patients with clear cell histology who had also undergone nephrectomy, which is the population of patients that is most commonly studied to gain drug approval in renal cell carcinoma.

“Patients randomized to continue tivozanib had a significantly higher disease control rate and median progression-free survival compared with those randomized to placebo,” said Dr. Dimitry Nosov of the N.N. Blokhin Russian Cancer Research Center in Moscow, who presented preliminary results of the randomized discontinuation trial at the annual congress of the European Society for Medical Oncology.

The trial involved a 16-week, open-label phase during which all patients received treatment with tivozanib, at a dosage of 1.5 mg/day for 3 weeks of a 4-week cycle. In all, 76 patients with progressive disease then stopped treatment, 78 of those with partial or complete responses continued open-label treatment, and 111 patients with stable disease were randomized to receive tivozanib or placebo for a further 12 weeks.

Dr. Nosov noted that the percentage of patients who remained progression free at 12 weeks following randomization to either tivozanib or placebo doubled with the active treatment (48% vs. 21%; P = .003).

The drug is reported to have greater potency for VEGF receptors 1, 2, and 3 than do other available agents, including Pfizer Inc.’s investigational agent axitinib, which may account for its low rate of “off-target” adverse events such as mucositis, stomatitis, fatigue, neutropenia, and hand-foot syndrome as seen in the trial. The most common side effects (all grades) reported for at least 10% of patients were hypertension (50%), dysphonia (22%), asthenia (approximately 13%), and diarrhea (12%).

“What’s extremely encouraging is the very good tolerability of this agent,” Dr. Tim Eisen, a professor at the University of Cambridge (England).

Dr. Eisen noted that although the number of patients who discontinued treatment was high at the end of the open-label treatment phase, it was also encouraging that progression-free survival was almost as good in patients who had stable disease and continued treatment with tivozanib as it was in those who had achieved a partial or complete response and received continued open-label treatment. “This might influence how we use the agent,” in clinical practice, he suggested.

The study was sponsored by AVEO Pharmaceuticals Inc. Dr. Nosov had no potential conflicts of interest, but several of his coauthors were employees of AVEO. The discussant, Dr. Eisen, has acted in advisory capacity for AVEO and GlaxoSmithKline, and has received research support and acted as an advisor to Bayer, Pfizer, and Roche.

MILAN – Tivozanib, an investigational agent, is not only active in the treatment of renal cell carcinoma, but is also associated with minimal “off target” toxicity, according to phase II study findings.

The tyrosine kinase inhibitor (TKI), which targets all three vascular epithelial growth factor (VEGF) receptors, was associated with an overall median progression-free survival of 11.8 months in a difficult-to-treat patient population; 17% of 272 patients had nonclear cell histology, 27% did not have prior nephrectomy, and 46% had received at least one prior treatment.

Median progression-free survival was slightly longer, at 14.8 months, in patients with clear cell histology who had also undergone nephrectomy, which is the population of patients that is most commonly studied to gain drug approval in renal cell carcinoma.

“Patients randomized to continue tivozanib had a significantly higher disease control rate and median progression-free survival compared with those randomized to placebo,” said Dr. Dimitry Nosov of the N.N. Blokhin Russian Cancer Research Center in Moscow, who presented preliminary results of the randomized discontinuation trial at the annual congress of the European Society for Medical Oncology.

The trial involved a 16-week, open-label phase during which all patients received treatment with tivozanib, at a dosage of 1.5 mg/day for 3 weeks of a 4-week cycle. In all, 76 patients with progressive disease then stopped treatment, 78 of those with partial or complete responses continued open-label treatment, and 111 patients with stable disease were randomized to receive tivozanib or placebo for a further 12 weeks.

Dr. Nosov noted that the percentage of patients who remained progression free at 12 weeks following randomization to either tivozanib or placebo doubled with the active treatment (48% vs. 21%; P = .003).

The drug is reported to have greater potency for VEGF receptors 1, 2, and 3 than do other available agents, including Pfizer Inc.’s investigational agent axitinib, which may account for its low rate of “off-target” adverse events such as mucositis, stomatitis, fatigue, neutropenia, and hand-foot syndrome as seen in the trial. The most common side effects (all grades) reported for at least 10% of patients were hypertension (50%), dysphonia (22%), asthenia (approximately 13%), and diarrhea (12%).

“What’s extremely encouraging is the very good tolerability of this agent,” Dr. Tim Eisen, a professor at the University of Cambridge (England).

Dr. Eisen noted that although the number of patients who discontinued treatment was high at the end of the open-label treatment phase, it was also encouraging that progression-free survival was almost as good in patients who had stable disease and continued treatment with tivozanib as it was in those who had achieved a partial or complete response and received continued open-label treatment. “This might influence how we use the agent,” in clinical practice, he suggested.

The study was sponsored by AVEO Pharmaceuticals Inc. Dr. Nosov had no potential conflicts of interest, but several of his coauthors were employees of AVEO. The discussant, Dr. Eisen, has acted in advisory capacity for AVEO and GlaxoSmithKline, and has received research support and acted as an advisor to Bayer, Pfizer, and Roche.

MILAN – Tivozanib, an investigational agent, is not only active in the treatment of renal cell carcinoma, but is also associated with minimal “off target” toxicity, according to phase II study findings.

The tyrosine kinase inhibitor (TKI), which targets all three vascular epithelial growth factor (VEGF) receptors, was associated with an overall median progression-free survival of 11.8 months in a difficult-to-treat patient population; 17% of 272 patients had nonclear cell histology, 27% did not have prior nephrectomy, and 46% had received at least one prior treatment.

Median progression-free survival was slightly longer, at 14.8 months, in patients with clear cell histology who had also undergone nephrectomy, which is the population of patients that is most commonly studied to gain drug approval in renal cell carcinoma.

“Patients randomized to continue tivozanib had a significantly higher disease control rate and median progression-free survival compared with those randomized to placebo,” said Dr. Dimitry Nosov of the N.N. Blokhin Russian Cancer Research Center in Moscow, who presented preliminary results of the randomized discontinuation trial at the annual congress of the European Society for Medical Oncology.

The trial involved a 16-week, open-label phase during which all patients received treatment with tivozanib, at a dosage of 1.5 mg/day for 3 weeks of a 4-week cycle. In all, 76 patients with progressive disease then stopped treatment, 78 of those with partial or complete responses continued open-label treatment, and 111 patients with stable disease were randomized to receive tivozanib or placebo for a further 12 weeks.

Dr. Nosov noted that the percentage of patients who remained progression free at 12 weeks following randomization to either tivozanib or placebo doubled with the active treatment (48% vs. 21%; P = .003).

The drug is reported to have greater potency for VEGF receptors 1, 2, and 3 than do other available agents, including Pfizer Inc.’s investigational agent axitinib, which may account for its low rate of “off-target” adverse events such as mucositis, stomatitis, fatigue, neutropenia, and hand-foot syndrome as seen in the trial. The most common side effects (all grades) reported for at least 10% of patients were hypertension (50%), dysphonia (22%), asthenia (approximately 13%), and diarrhea (12%).

“What’s extremely encouraging is the very good tolerability of this agent,” Dr. Tim Eisen, a professor at the University of Cambridge (England).

Dr. Eisen noted that although the number of patients who discontinued treatment was high at the end of the open-label treatment phase, it was also encouraging that progression-free survival was almost as good in patients who had stable disease and continued treatment with tivozanib as it was in those who had achieved a partial or complete response and received continued open-label treatment. “This might influence how we use the agent,” in clinical practice, he suggested.

The study was sponsored by AVEO Pharmaceuticals Inc. Dr. Nosov had no potential conflicts of interest, but several of his coauthors were employees of AVEO. The discussant, Dr. Eisen, has acted in advisory capacity for AVEO and GlaxoSmithKline, and has received research support and acted as an advisor to Bayer, Pfizer, and Roche.

MILAN – Tivozanib, an investigational agent, is not only active in the treatment of renal cell carcinoma, but is also associated with minimal “off target” toxicity, according to phase II study findings.

The tyrosine kinase inhibitor (TKI), which targets all three vascular epithelial growth factor (VEGF) receptors, was associated with an overall median progression-free survival of 11.8 months in a difficult-to-treat patient population; 17% of 272 patients had nonclear cell histology, 27% did not have prior nephrectomy, and 46% had received at least one prior treatment.

Median progression-free survival was slightly longer, at 14.8 months, in patients with clear cell histology who had also undergone nephrectomy, which is the population of patients that is most commonly studied to gain drug approval in renal cell carcinoma.

“Patients randomized to continue tivozanib had a significantly higher disease control rate and median progression-free survival compared with those randomized to placebo,” said Dr. Dimitry Nosov of the N.N. Blokhin Russian Cancer Research Center in Moscow, who presented preliminary results of the randomized discontinuation trial at the annual congress of the European Society for Medical Oncology.

The trial involved a 16-week, open-label phase during which all patients received treatment with tivozanib, at a dosage of 1.5 mg/day for 3 weeks of a 4-week cycle. In all, 76 patients with progressive disease then stopped treatment, 78 of those with partial or complete responses continued open-label treatment, and 111 patients with stable disease were randomized to receive tivozanib or placebo for a further 12 weeks.

Dr. Nosov noted that the percentage of patients who remained progression free at 12 weeks following randomization to either tivozanib or placebo doubled with the active treatment (48% vs. 21%; P = .003).

The drug is reported to have greater potency for VEGF receptors 1, 2, and 3 than do other available agents, including Pfizer Inc.’s investigational agent axitinib, which may account for its low rate of “off-target” adverse events such as mucositis, stomatitis, fatigue, neutropenia, and hand-foot syndrome as seen in the trial. The most common side effects (all grades) reported for at least 10% of patients were hypertension (50%), dysphonia (22%), asthenia (approximately 13%), and diarrhea (12%).

“What’s extremely encouraging is the very good tolerability of this agent,” Dr. Tim Eisen, a professor at the University of Cambridge (England).

Dr. Eisen noted that although the number of patients who discontinued treatment was high at the end of the open-label treatment phase, it was also encouraging that progression-free survival was almost as good in patients who had stable disease and continued treatment with tivozanib as it was in those who had achieved a partial or complete response and received continued open-label treatment. “This might influence how we use the agent,” in clinical practice, he suggested.

The study was sponsored by AVEO Pharmaceuticals Inc. Dr. Nosov had no potential conflicts of interest, but several of his coauthors were employees of AVEO. The discussant, Dr. Eisen, has acted in advisory capacity for AVEO and GlaxoSmithKline, and has received research support and acted as an advisor to Bayer, Pfizer, and Roche.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.