Gollob Jared A, Rathmell W Kimryn, Richmond Tina M, Marino Christine B, Miller Elizabeth K, Grigson Gayle, Watkins Catharine, Gu Lin, Peterson Bercedis L, Wright John J
Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J Clin Oncol. 2007 Aug 1;25(22):3288-95. doi: 10.1200/JCO.2007.10.8613.
We 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).
Between 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.
The response rate was 33% (95% CI, 19% to 49%; 13 of 40 patients), including 28% partial responses (n = 11) and 5% complete responses (n = 2). Responses were seen in treatment-naïve 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% CI, 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.
The combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-naïve 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.
我们开展这项研究，以确定索拉非尼联合干扰素α-2b（IFN-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。
2004年11月至2006年10月期间，两个研究地点的40例患者入组了索拉非尼联合IFN-α-2b的II期试验。治疗方案为：每8周为一个周期，索拉非尼400 mg口服，每日2次，IFN-α-2b 1000万U皮下注射，每周3次，随后休息2周。患者在疾病进展前可接受额外的治疗周期。因毒性反应，两种药物允许各减少剂量50%一次。
缓解率为33%（95%CI，19%至49%；40例患者中有13例），包括28%的部分缓解（n = 11）和5%的完全缓解（n = 2）。初治患者和接受过白细胞介素-2（IL-2）治疗的患者在前两个周期内均出现缓解。缓解持续时间的中位数为12个月。中位随访时间为14个月，无进展生存期的中位数为10个月（95%CI，8至18个月），总生存期的中位数尚未达到。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级毒性反应不常见，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。
索拉非尼和IFN-α-2b联合用药对初治和接受过IL-2治疗的RCC患者具有显著活性。毒性反应超过了单药治疗，但减少剂量和周期之间的休息允许进行长期治疗。一项更大规模的随机试验将确定该方案与单用索拉非尼相比是否具有任何优势。
