Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer
Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer
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DOI：
10.1200/jco.2007.10.8613
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发表时间：
2007-08-01
影响因子：
45.3
通讯作者：
Wright, John J.
中科院分区：
文献类型：
--
作者：
Gollob, Jared A.;Rathmell, W. Kimryn;Wright, John J.
我们开展了这项研究，以确定索拉非尼联合干扰素α-2b(干扰素-α-2b)作为转移性肾细胞癌(RCC)一线或二线治疗的活性和耐受性。治疗包括索拉非尼400 mg口服，2次/d加干扰素-α-2b 1000万U皮下注射，每周3次，然后休息2周，疗程8周。患者有资格接受额外的治疗周期，直到疾病进展。结果总有效率为33%(95%氯，19%~49%；40例患者中13例)，其中部分缓解(28%)11例，完全缓解(5%)2例。在治疗初治和白介素2(IL-2)治疗的患者中，在前两个周期内出现了反应。中位有效时间为12个月。中位随访时间为14个月，中位无进展生存期为10个月(95%CI，8~18个月)，中位总生存期尚未达到。疲劳、厌食、贫血、腹泻、低磷血症、皮疹、恶心和体重减轻是最常见的毒性反应。3级毒性很少见，但包括低磷血症、中性粒细胞减少、皮疹、疲劳和贫血。65%的患者需要减少剂量。结论索拉非尼联合干扰素-α-2b治疗初治和IL-2治疗的肾癌患者具有显著的疗效。毒性超过了这两种药物的单独使用，但剂量减少和周期间隔允许进行慢性治疗。一项更大规模的随机试验将确定该方案与单独使用索拉非尼相比是否有任何优势。
PurposeWe undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b ( IFN-alpha-2b) as first-or second-line therapy in metastatic renal cell cancer ( RCC).Patients and MethodsBetween November 2004 and October 2006, 40 patients at two sites were enrolled onto a phase II trial of sorafenib plus IFN-alpha-2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN-alpha-2b 10 million U subcutaneously three times a week followed by a 2-week break. Patients were eligible to receive additional cycles of therapy until disease progression. Dose reduction of both drugs by 50% was permitted once for toxicity.ResultsThe response rate was 33% ( 95% Cl, 19% to 49%; 13 of 40 patients), including 28% partial responses ( n = 11) and 5% complete responses ( n = 2). Responses were seen in treatment-nai ve and interleukin-2 ( IL-2) -treated patients within the first two cycles. The median duration of response was 12 months. With a median follow-up time of 14 months, median progression-free survival time was 10 months ( 95% Cl, 8 to 18 months), and median overall survival time has not yet been reached. Fatigue, anorexia, anemia, diarrhea, hypophosphatemia, rash, nausea, and weight loss were the most common toxicities. Grade 3 toxicities were uncommon but included hypophosphatemia, neutropenia, rash, fatigue, and anemia. Dose reductions were required in 65% of patients.ConclusionThe combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-nai r ve and IL-2 -treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone.