Ryan Christopher W, Goldman Bryan H, Lara Primo N, Mack Philip C, Beer Tomasz M, Tangen Catherine M, Lemmon Dianne, Pan Chong-Xian, Drabkin Harry A, Crawford E David
Oregon Health and Science University, Portland, OR, USA.
J Clin Oncol. 2007 Aug 1;25(22):3296-301. doi: 10.1200/JCO.2007.11.1047.
This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma.
Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 x 10(6) U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate.
Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens.
The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.
本II期研究评估了α-干扰素2b与索拉非尼（一种Raf和多种受体酪氨酸激酶抑制剂）联合治疗晚期肾癌患者的活性。
符合条件的患者患有伴有透明细胞成分的转移性或不可切除性肾癌，既往未接受过全身治疗，体能状态为0至1，且疾病可测量。治疗方案为：α-干扰素2b 10×10⁶U皮下注射，每周3次，索拉非尼400mg口服，每日2次。主要终点为根据实体瘤疗效评价标准确认的缓解率。
62例可评估患者中有12例（19%）获得了确认的客观缓解。另外31例（50%）患者的最佳疗效为未确认的部分缓解或疾病稳定。中位无进展生存期为7个月（95%CI，4至11个月）。最常见的不良事件为乏力、厌食、贫血、腹泻、恶心、寒战/发冷、白细胞减少、发热和转氨酶升高。在18份存档肿瘤标本中有4份（22%）检测到了VHL基因（即VHL综合征相关基因，Von Hippel-Lindau gene）突变。
索拉非尼与干扰素联合治疗晚期肾癌的确认缓解率高于单独使用干扰素或索拉非尼时的预期。该联合治疗的毒性主要由干扰素常见的不良事件主导，这限制了该治疗方案的进一步开展。
