Phase III, Randomized, Placebo-Controlled Study of Docetaxel in Combination With Zibotentan in Patients With Metastatic Castration-Resistant Prostate Cancer
Phase III, Randomized, Placebo-Controlled Study of Docetaxel in Combination With Zibotentan in Patients With Metastatic Castration-Resistant Prostate Cancer
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DOI：
10.1200/jco.2012.46.4149
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发表时间：
2013-05-10
影响因子：
45.3
通讯作者：
Moul, Judd W.
中科院分区：
文献类型：
--
作者：
Fizazi, Karim S.;Higano, Celestia S.;Moul, Judd W.
目的作为热情的一部分（Endothelin A Use）计划，研究了口服特异性内皮素A受体拮抗剂zibotentan（ZD 4054）与多西他赛联合治疗转移性去势抵抗性前列腺癌（CRPC）患者的疗效和安全性。患者在21天为一周期的第1天接受静脉多西他赛75 mg/m2+口服zibotentan 10 mg或安慰剂每日一次。主要终点是总生存期（OS）。次要终点包括疼痛和前列腺特异性抗原（PSA）进展的时间，疼痛和PSA反应，无进展生存期，健康相关的生活质量，和safety.ResultsA共1,052例患者接受研究治疗（紫杉醇-zibotentan，n = 524;紫杉醇-安慰剂，n = 528）。截至数据截止时，分别有277人和280人死亡。与接受紫杉醇-安慰剂的患者相比，接受紫杉醇-zibotentan的患者的OS无差异（风险比，1.00; 95% CI，0.84 - 1.18; P = 0.963）。在次要终点上没有观察到显著差异，包括疼痛进展时间（中位数分别为9.3和10.0个月）或疼痛缓解（比值比，0.84; 95%CI，0.61至1.16; P = 0.283）。齐博腾坦组和安慰剂组的中位死亡时间分别为20.0个月和19.2个月。最常见的不良事件在zibotentan治疗的患者外周水肿（52.7%），腹泻（35.4%），脱发（33.9%），恶心（33.3%.ConclusionDocetaxel加zibotentan 10 mg/d并没有导致一个显着改善OS相比，多西他赛加安慰剂转移性CRPC患者。(C)2013年美国临床肿瘤学会
PurposeAs part of the ENTHUSE (Endothelin A Use) program, the efficacy and safety of zibotentan (ZD4054), an oral specific endothelin A receptor antagonist, has been investigated in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (CRPC).Patients and MethodsIn this randomized, double-blind, placebo-controlled, phase III study, patients received intravenous docetaxel 75 mg/m(2) on day 1 of 21-day cycles plus oral zibotentan 10 mg or placebo once daily. The primary end point was overall survival (OS). Secondary end points included time to pain and prostate-specific antigen (PSA) progression, pain and PSA response, progression-free survival, health-related quality of life, and safety.ResultsA total of 1,052 patients received study treatment (docetaxel-zibotentan, n = 524; docetaxel-placebo, n = 528). At the time of data cutoff, there had been 277 and 280 deaths, respectively. There was no difference in OS for patients receiving docetaxel-zibotentan compared with those receiving docetaxel-placebo (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P = .963). No significant differences were observed on secondary end points, including time to pain progression (median 9.3 v 10.0 months, respectively) or pain response (odds ratio, 0.84; 95% CI, 0.61 to 1.16; P = .283). The median time to death was 20.0 and 19.2 months for the zibotentan and placebo groups, respectively. The most commonly reported adverse events in zibotentan-treated patients were peripheral edema (52.7%), diarrhea (35.4%), alopecia (33.9%), and nausea (33.3%).ConclusionDocetaxel plus zibotentan 10 mg/d did not result in a significant improvement in OS compared with docetaxel plus placebo in patients with metastatic CRPC. (C) 2013 by American Society of Clinical Oncology