Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.
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DOI：
10.1056/nejmoa1503747
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发表时间：
2015-08-20
期刊：
影响因子：
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通讯作者：
DiPaola RS
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作者：
Sweeney CJ;Chen YH;Carducci M;Liu G;Jarrard DF;Eisenberger M;Wong YN;Hahn N;Kohli M;Cooney MM;Dreicer R;Vogelzang NJ;Picus J;Shevrin D;Hussain M;Garcia JA;DiPaola RS
自20世纪40年代以来，雄激素剥夺疗法（ADT）一直是转移性前列腺癌治疗的支柱。我们评估了ADT联合多西他赛联合治疗是否会导致比ADT单药治疗更长的总生存期。我们将患有转移性、前列腺癌敏感性的男性患者分配接受ADT+多西他赛（剂量为75 mg/m2体表面积，每3周一次，共6个周期）或ADT单药治疗。主要目的是检验以下假设：在治疗早期接受多西他赛加用ADT的患者的中位总生存期比接受ADT单药治疗的患者长33.3%。共有790例患者（中位年龄63岁）接受了随机化。中位随访28.9个月后，ADT+多西他赛（联合治疗）的中位总生存期比ADT单药治疗长13.6个月（57.6个月vs. 44.0个月;联合治疗组死亡的风险比为0.61; 95%置信区间[CI]为0.47 - 0.80; P<0.001）。联合用药组至生化、症状或放射学进展的中位时间为20.2个月，而ADT单药组为11.7个月（风险比，0.61; 95%CI，0.51 - 0.72; P<0.001）。12个月时，联合治疗组前列腺特异性抗原水平低于0.2 ng/ml的比例为27.7%，而ADT单药组为16.8%（P<0.001）。在联合治疗组中，3级或4级发热性中性粒细胞减少的发生率为6.2%，3级或4级感染伴中性粒细胞减少的发生率为2.3%，3级感觉神经病变和3级运动神经病变的发生率为0.5%。在ADT治疗转移性前列腺癌开始时接受6个周期的多西他赛治疗，总生存期显著长于ADT单药治疗。（由国家癌症研究所和其他机构资助; ClinicalTrials.gov编号，NCT 00309985。
Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.)