Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer.
Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer.
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DOI：
10.1056/nejmoa1001294
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发表时间：
2010-07-29
影响因子：
158.5
通讯作者：
Young, J.
中科院分区：
文献类型：
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作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
背景：西普鲁切尔-T是一种自体主动细胞免疫疗法，已有证据表明它能有效降低男性去势耐受转移前列腺癌患者的死亡风险。方法：在这项双盲、安慰剂对照的多中心3期试验中，我们以2：1的比例随机分配512名患者接受西普鲁切尔-T(341名患者)或安慰剂(171名患者)的静脉注射，每两周一次，共三次输液。结果：与安慰剂组相比，治疗组的死亡风险相对降低22%(风险比0.78；95%可信区间0.61~0.98；P=0.03)。这一减少意味着中位生存期提高了4.1个月(siPuleucel-T组为25.8个月，而安慰剂组为21.7个月)。36个月存活率为31.7%，而安慰剂组为23.0%。用未调整的COX模型和对数等级检验(风险比，0.77；95%CI，0.61~0.97；P=0.02)和研究治疗后调整多西紫杉醇的使用(风险比，0.78；95%CI，0.62~0.98；P=0.03)来观察治疗效果。两个研究组达到目标疾病进展的时间相似。在接受西普鲁尔-T治疗的患者中观察了对免疫抗原的免疫应答。与安慰剂组相比，西普鲁切尔-T组更常见的不良事件包括寒战、发热和头痛。结论：西普鲁切尔-T的使用延长了转移性去势抵抗前列腺癌患者的总体生存时间。没有观察到对疾病进展时间的影响。(由Dendreon资助；ClinicalTrials.gov编号，NCT00065442。)N Engl J Med 2010；363：411-22。
Background: Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer.Methods: In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase.Results: In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache.Conclusions: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)N Engl J Med 2010;363:411-22.