Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure
Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure
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DOI：
10.1111/j.1464-410x.2012.11404.x
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发表时间：
2013-01-01
影响因子：
4.5
通讯作者：
de Wit, Ronald
中科院分区：
文献类型：
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作者：
Meulenbeld, Hielke J.;Bleuse, Jean P.;de Wit, Ronald
目的观察丹那替的疗效和毒性（以前的PHA-739358）在两种不同的给药方案中以等效的剂量强度静脉内给药，用于转移性去势抵抗性前列腺癌患者，在基于紫杉醇的治疗后疾病进展。（1：1比率），在第1、8和15天接受Danusertib 330 mg/m（2），静脉注射6小时（A组，n=43）或500 mg/m（2），静脉注射24小时，第1天和第15天（B组，n = 38），本探索性研究的主要终点是3个月时的PSA应答率。A组和B组分别有31/43和29/38例患者可用于主要终点的评估，两组的中位无进展生存期均为12周，两组各有1例患者出现PSA应答;最佳总体缓解为8例患者病情稳定，（18.6%）和13 A组和B组分别有11例（34.2%）患者（13.6%）接受治疗的患者病情稳定>= 6个月。最常见的3级和4级药物相关的不良事件是中性粒细胞减少，发生在37.2%（A组）和15.8%（B组）的patients.ConclusionDanusertib单药治疗去势抵抗性前列腺癌患者的疗效最低。需要进一步的研究来建立预测缓解或延长疾病稳定的特异性生物标志物。
ObjectiveTo determine the efficacy and toxicity of danusertib (formerly PHA-739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment.Patients and MethodsIn this open-label, multicentre phase II trial 88 patients were randomly assigned (1: 1 ratio) to receive either danusertib 330 mg/m(2) over 6 h i.v. on days 1, 8 and 15 (arm A, n=43) or 500 mg/m(2) over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks.The primary endpoint chosen for this exploratory study was PSA response rate at 3 months.ResultsSixty patients (31/43 in arm A and 29/38 in arm B) were evaluable for the primary endpoint.Median progression-free survival was 12 weeks in both arms.PSA response occurred in one patient in each arm; best overall response was stable disease in eight (18.6%) and 13 (34.2%) patients in arms A and B, respectively.Eleven out of 81 (13.6%) treated patients had stable disease for >= 6 months.Danusertib was generally well tolerated; the most common grade 3 and 4 drug-related adverse event was neutropenia which occurred in 37.2% (arm A) and 15.8% (arm B) of the patients.ConclusionDanusertib monotherapy shows minimal efficacy in patients with castration-resistant prostate cancer. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization.