Docetaxel prolongs life in men with hormone refractory prostate cancer
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《英国医生杂志》
Docetaxel (Taxotere) in combination with prednisolone helps men with advanced, hormone refractory prostate cancer live longer and enjoy more time free of pain, compared with mitoxantrone and prednisone, the current standard treatment for these patients, a US study shows.
Treatment with mitoxantrone and prednisone is known to reduce pain and improves the quality of life in men with advanced, hormone refractory prostate cancer, but it has never been shown to improve survival.
The study抯 researchers, led by Dr Ian Tannock from the Department of Medical Oncology and Hematology at Princess Margaret Hospital in Toronto, set out to determine whether docetaxel prolongs lives (New England Journal of Medicine 2004;354:1502-12).
The researchers followed 1006 men with metastatic, hormone refractory prostate cancer from March 2000 to June 2002. The randomised non-blinded study was conducted at 24 medical centres in the United States. The participants did not get to choose which regimen they received but knew which they would be getting.
To be eligible patients had to have confirmed adenocarcinoma of the prostate, with clinical or radiological evidence of metastatic disease. They also had to have experienced disease progression during hormonal treatment and to have been receiving primary androgen ablation treatment as maintenance treatment. At least four weeks had to have elapsed between the withdrawal of anti-androgens (or six weeks in the case of bicalutamide) and enrolment to avoid the possibility of confounding as a result of the response to withdrawal of the anti-androgen treatment.
The requirement of disease progression was shown by increasing serum concentrations of prostate specific antigen (PSA) on three consecutive measurements obtained at least one week apart or by findings on physical examination or imaging studies.
The men were each given 5 mg of prednisone twice daily and were randomly assigned to one of three regimens: 12 mg of mitoxantrone per square metre of body surface area every three weeks, 75 mg of docetaxel per square metre every three weeks, or 30 mg of docetaxel per square metre weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, PSA concentrations, and quality of life. The goal of the analysis was to compare the two docetaxel regimens with the mitoxantrone one.
The hazard ratio for death in the group of men who were given docetaxel every three weeks, compared with men in the mitoxantrone group, was 0.76 (95% confidence interval 0.62 to 0.94; P=0.009). The corresponding ratio for the men given weekly docetaxel was 0.91 (0.75 to 1.11; P=0.36). Median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every three weeks, and 17.4 months in the group given weekly docetaxel.
In the mitoxantrone group 32% of the men had at least a 50% drop in serum PSA concentration. The drop was 45% for the higher 75 mg dose of docetaxel and 48% for the more frequent 30 mg dose (P<0.001 for both comparisons with mitoxantrone). Adverse events, however, were more common in the two docetaxel groups, and these included fatigue, nausea or vomiting, hair loss, diarrhoea, anorexia, and neuropathy.
"Our findings provide evidence that cytotoxic chemotherapy can significantly prolong survival among men with hormone-refractory prostate cancer," the authors wrote. "Our data suggest that docetaxel plus prednisone is the preferred option for most patients with hormone-refractory prostate cancer."(New York Scott Gottlieb)
Treatment with mitoxantrone and prednisone is known to reduce pain and improves the quality of life in men with advanced, hormone refractory prostate cancer, but it has never been shown to improve survival.
The study抯 researchers, led by Dr Ian Tannock from the Department of Medical Oncology and Hematology at Princess Margaret Hospital in Toronto, set out to determine whether docetaxel prolongs lives (New England Journal of Medicine 2004;354:1502-12).
The researchers followed 1006 men with metastatic, hormone refractory prostate cancer from March 2000 to June 2002. The randomised non-blinded study was conducted at 24 medical centres in the United States. The participants did not get to choose which regimen they received but knew which they would be getting.
To be eligible patients had to have confirmed adenocarcinoma of the prostate, with clinical or radiological evidence of metastatic disease. They also had to have experienced disease progression during hormonal treatment and to have been receiving primary androgen ablation treatment as maintenance treatment. At least four weeks had to have elapsed between the withdrawal of anti-androgens (or six weeks in the case of bicalutamide) and enrolment to avoid the possibility of confounding as a result of the response to withdrawal of the anti-androgen treatment.
The requirement of disease progression was shown by increasing serum concentrations of prostate specific antigen (PSA) on three consecutive measurements obtained at least one week apart or by findings on physical examination or imaging studies.
The men were each given 5 mg of prednisone twice daily and were randomly assigned to one of three regimens: 12 mg of mitoxantrone per square metre of body surface area every three weeks, 75 mg of docetaxel per square metre every three weeks, or 30 mg of docetaxel per square metre weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, PSA concentrations, and quality of life. The goal of the analysis was to compare the two docetaxel regimens with the mitoxantrone one.
The hazard ratio for death in the group of men who were given docetaxel every three weeks, compared with men in the mitoxantrone group, was 0.76 (95% confidence interval 0.62 to 0.94; P=0.009). The corresponding ratio for the men given weekly docetaxel was 0.91 (0.75 to 1.11; P=0.36). Median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every three weeks, and 17.4 months in the group given weekly docetaxel.
In the mitoxantrone group 32% of the men had at least a 50% drop in serum PSA concentration. The drop was 45% for the higher 75 mg dose of docetaxel and 48% for the more frequent 30 mg dose (P<0.001 for both comparisons with mitoxantrone). Adverse events, however, were more common in the two docetaxel groups, and these included fatigue, nausea or vomiting, hair loss, diarrhoea, anorexia, and neuropathy.
"Our findings provide evidence that cytotoxic chemotherapy can significantly prolong survival among men with hormone-refractory prostate cancer," the authors wrote. "Our data suggest that docetaxel plus prednisone is the preferred option for most patients with hormone-refractory prostate cancer."(New York Scott Gottlieb)