索拉非尼联合白细胞介素-2 与索拉非尼单药治疗转移性肾细胞癌：ROSORC 试验。

Sorafenib with interleukin-2 vs sorafenib alone in metastatic renal cell carcinoma: the ROSORC trial.

机构信息

Department of Medical Oncology, Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy.

出版信息

Br J Cancer. 2011 Apr 12;104(8):1256-61. doi: 10.1038/bjc.2011.103. Epub 2011 Mar 29.

BACKGROUND

Preclinical investigations support combining sorafenib with IL-2 in the treatment of metastatic renal cell carcinoma (mRCC).

METHODS

In this open-label, phase II study, 128 patients with mRCC were randomised to receive oral sorafenib, 400 mg twice daily, plus subcutaneous IL-2, 4.5 million international units (MIU) five times per week for 6 in every 8 weeks, or sorafenib alone. After enrolment of the first 40 patients, IL-2 dose was reduced to improve the tolerability.

RESULTS

After a median follow-up of 27 months, median progression-free survival (PFS) was 33 weeks with sorafenib plus IL-2, and 30 weeks with sorafenib alone (P=0.109). For patients receiving the initial higher dose of IL-2, median PFS was 43 weeks vs 31 weeks for those receiving the lower dose. The most common adverse events were asthenia, hand-foot syndrome, hypertension, and diarrhoea. Grade 3-4 adverse events were reported for 38 and 25% of patients receiving combination and single-agent treatment, respectively.

CONCLUSION

The combination of sorafenib and IL-2 did not demonstrate improved efficacy vs sorafenib alone. Improvements in PFS appeared greater in patients receiving higher-dose IL-2.

背景

临床前研究支持将索拉非尼与白细胞介素 2（IL-2）联合用于治疗转移性肾细胞癌（mRCC）。

方法

在这项开放标签、II 期研究中，128 例 mRCC 患者被随机分配接受口服索拉非尼，每日两次，每次 400mg，联合每周 5 次皮下注射白细胞介素 2，每次 4.5 百万国际单位（MIU），每 8 周的 6 周内用药，或单独使用索拉非尼。在纳入前 40 例患者后，降低了白细胞介素 2 的剂量以提高耐受性。

结果

中位随访 27 个月后，索拉非尼联合白细胞介素 2组和索拉非尼单药组的中位无进展生存期（PFS）分别为 33 周和 30 周（P=0.109）。对于接受初始较高剂量白细胞介素 2 的患者，中位 PFS 为 43 周，而接受较低剂量白细胞介素 2 的患者为 31 周。最常见的不良反应是乏力、手足综合征、高血压和腹泻。联合和单药治疗组分别有 38%和 25%的患者报告了 3-4 级不良反应。