Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.
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.
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.
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.
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.)
Sipuleucel-T 是一种自体活性细胞免疫疗法，已证明可降低转移性去势抵抗性前列腺癌患者的死亡风险。
在这项双盲、安慰剂对照、多中心 3 期临床试验中，我们以 2:1 的比例将 512 名患者随机分配接受 sipuleucel-T（341 名患者）或安慰剂（171 名患者）静脉输注，每 2 周一次，共输注 3 次。主要终点是总生存期，采用分层 Cox 回归模型分析，该模型根据基线前列腺特异性抗原（PSA）和乳酸脱氢酶水平进行调整。
与安慰剂组相比，Sipuleucel-T 组的死亡风险降低了 22%（风险比，0.78；95%置信区间 [CI]，0.61 至 0.98；P=0.03）。中位生存期延长了 4.1 个月（Sipuleucel-T 组为 25.8 个月，安慰剂组为 21.7 个月）。Sipuleucel-T 组的 36 个月生存率为 31.7%，安慰剂组为 23.0%。使用未调整的 Cox 模型和对数秩检验也观察到治疗效果（风险比，0.77；95%CI，0.61 至 0.97；P=0.02），并且在研究治疗后使用多西他赛进行调整后也是如此（风险比，0.78；95%CI，0.62 至 0.98；P=0.03）。两组患者的客观疾病进展时间相似。接受 sipuleucel-T 治疗的患者出现了针对免疫原的免疫反应。与安慰剂组相比，Sipuleucel-T 组更常报告的不良事件包括寒战、发热和头痛。
Sipuleucel-T 可延长转移性去势抵抗性前列腺癌患者的总生存期。未观察到对疾病进展时间的影响。（由 Dendreon 资助；ClinicalTrials.gov 编号，NCT00065442）
