Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer.
Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer.
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DOI：
10.1111/j.1464-410x.2008.08327.x
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发表时间：
2009-06
影响因子：
4.5
通讯作者：
Dahut WL
中科院分区：
文献类型：
--
作者：
Aragon-Ching JB;Jain L;Gulley JL;Arlen PM;Wright JJ;Steinberg SM;Draper D;Venitz J;Jones E;Chen CC;Figg WD;Dahut WL
在转移性去势抵抗性前列腺癌（CRPC）患者中，单独使用放射学和临床标准确定索拉非尼是否与4个月无进展生存率改善相关。次要终点包括药代动力学、毒性分析和总生存期。这是一项开放标签、II期、2阶段设计，重点关注第二阶段的结果，因为在第一阶段完成后修改了进展标准。索拉非尼以400 mg每日两次口服给药，28天为一个周期。每4周进行一次临床和实验室评估，每8周进行一次影像学扫描。24例患者进入第二阶段。患者特征包括中位（范围）年龄为66岁（49 - 85岁），研究期间PSA为68.45 ng/mL（5.8 - 995），Gleason评分为8分（6 - 9分），ECOG评分为1分（n=17）。21/24例既往接受过多西他赛化疗。所有患者均有骨转移，单独（n=11）或伴有软组织疾病（n=13）。1例患者部分缓解。10例患者病情稳定（中位持续时间：18周，范围：15 - 48周）。中位潜在随访时间为27.2个月，中位无进展生存期为3.7个月，中位总生存期为18.0个月。在整个46例患者的试验中，中位生存期为18.3个月。最常见的毒性包括手足皮肤反应（9例患者为2级，3例患者为3级）、皮疹、LFT异常和疲乏。索拉非尼作为转移性CRPC的二线治疗具有中等活性。
To determine if sorafenib is associated with an improved 4-month probability of progression-free survival using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer (CRPC). Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival. This was an open-label, phase II, 2 stage design, focusing on the results from the second stage since criteria for progression were modified after completion of the first stage. Sorafenib was given daily at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, radiographic scans were obtained every 8 weeks. Twenty-four patients were accrued in the second stage. Patient characteristics included a median (range) age of 66 (49 – 85), on-study PSA of 68.45 ng/mL (5.8 – 995), Gleason of 8 (6 – 9), and ECOG of 1 (n=17). 21/24 had prior chemotherapy with docetaxel. All patients had bony metastases, either alone (n=11) or with soft tissue disease (n=13). One patient had a partial response. Ten patients had stable disease (median duration: 18 weeks, range: 15 – 48 weeks). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients, median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (Grade 2 in 9 patients, Grade 3 in 3 patients), rash, LFT abnormalities, and fatigue. Sorafenib has moderate activity as 2nd line treatment in metastatic CRPC.