Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 study group
Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 study group
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DOI：
10.1200/jco.2007.14.8288
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发表时间：
2008-05-01
影响因子：
45.3
通讯作者：
Hersh, Evan
中科院分区：
文献类型：
--
作者：
McDermott, David F.;Sosman, Jeffrey A.;Hersh, Evan
Purpose本II期研究评估了索拉非尼加达卡巴嗪在晚期melanoma.Patients and MethodsThis随机、双盲、安慰剂对照、多中心研究中的疗效和安全性，该研究招募了未经化疗的III期（不可切除）或IV期黑色素瘤患者。共101例患者接受安慰剂+达卡巴嗪（n = 50）或索拉非尼+达卡巴嗪（n = 51）。在21天周期的第1天，患者接受达卡巴嗪1，000 mg/m2静脉给药，最多16个周期。口服索拉非尼400 mg或安慰剂，每天两次，连续给药。主要终点是独立评估的无进展生存期（PFS）。二级和三级终点包括疾病进展时间（TTP），反应率和总生存期（OS）。索拉非尼加达卡巴嗪组的中位PFS为21.1周，安慰剂加达卡巴嗪组为11.7周（风险比[HR]，0.665; P = 0.068）。索拉非尼+达卡巴嗪组在6个月和9个月时的PFS率和TTP（中位数，21.1 v11.7周; HR，0.619）有统计学显著性改善，OS无差异（安慰剂+达卡巴嗪组和索拉非尼+达卡巴嗪组的中位数分别为51.3 v45.6周; HR，1.022）。该方案耐受性良好，并有一个可管理的毒性profile.ConclusionSorafenib加达卡巴嗪是晚期黑色素瘤患者的耐受性良好，并取得了令人鼓舞的改善PFS。基于这些发现，需要在该患者人群中进行联合用药的额外研究。
Purpose This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma.Patients and MethodsThis randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naive patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine ( n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m(2) for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progression-free survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival ( OS).ResultsMedian PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm ( hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP ( median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed ( median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile.ConclusionSorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.