Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer
Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer
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DOI：
10.1200/jco.2005.04.5252
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发表时间：
2006-07-01
影响因子：
45.3
通讯作者：
Hershberg, Robert M.
中科院分区：
文献类型：
--
作者：
Small, Eric J.;Schellhammer, Paul F.;Hershberg, Robert M.
ipuleucel- t （APC8015）是一种实验性免疫治疗产品，旨在刺激t细胞对前列腺酸的免疫。磷酸酶。在一项安慰剂对照研究中，进行了一项III期研究来评估sipuleucel-T的安全性和有效性。患者和方法127例无症状转移激素难治性前列腺癌（HRPC）患者按2:1的比例随机分配，每2周输注3次sipuleucil - t （n = 82）或安慰剂（n = 45）。在疾病进展方面，安慰剂患者可以接受APC8015F，这是一种用冷冻白细胞分离细胞制成的产品。结果127例患者中，115例患者在数据分析时病情进展，所有患者随访36个月。sipuleucel-T组到疾病进展的中位时间（TTP）为11.7周，而安慰剂组为10.0周（P = 0.052, log-rank；风险比[HR]， 1.45; 95%CI， 0.99至2.11）。安慰剂组的中位生存期为21.4个月，安慰剂组的中位生存期为25.9个月（P = 0.01, log-rank； HR, 1.70; 95%CI, 1.13 ~ 2.56）。在使用Cox多变量回归模型调整预后因素后，治疗仍然是总生存的一个强有力的独立预测因子（P = 0.002， Wald检验；HR, 2.12; 95%CI， 1.31至3.44）。8周时t细胞刺激与预处理的中位比例在单核t治疗患者中高出8倍(16.9 vs 1.99； P
PurposeSipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid. phosphatase. A phase III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study.Patients and MethodsA total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 'ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks. On disease progression, placebo patients could receive APC8015F, a product made with frozen leukapheresis cells.ResultsOf the 127 patients, 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 months. The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0 weeks for placebo (P =.052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to 2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo (P =.01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using a Cox multivariable regression model (P =.002, Wald test; HR, 2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99; P