Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BJU Int. 2011 Dec;108(11):1813-9. doi: 10.1111/j.1464-410X.2011.10281.x. Epub 2011 Apr 11.
What's known on the subject? and What does the study add? Interim result of this study had shown promising efficacy, with response rate of 14.7% and median PFS of 7.4 months, and good tolerability of sorafenib in previously-treated Japanese patients with metastatic RCC. Final result of the study adds: (1) the median overall survival of 25.3 months, which is longer than that in the global phase III study TARGET; (2) the response rate which elevated to 19.4% because of 6 late responders achieved after 9.2 months or longer of SD period; (3) lack of either unknown adverse events nor cumulative toxicity in the long-term use of sorafenib.
• To explore the long-term efficacy and safety of sorafenib in Japanese patients with metastatic renal cell carcinoma (RCC) in a phase II trial.
• In all, 131 Japanese patients with metastatic RCC who had received nephrectomy and failed at least one cytokine-containing systemic therapy received continuous sorafenib 400 mg twice daily, and the efficacy and safety parameters were evaluated in these patients, including objective response rate, progression-free survival and overall survival.
• Of the total, 129 patients were valid for intention-to-treat analyses and 131 patients were valid for safety analyses. • Twenty-five patients (19.4%) had confirmed partial response and 87 patients (67.4%) had stable disease as best overall response. The 25 patients included six late-responders who achieved response after 9.2 months or longer of stable disease. The objective response rate and disease control rate were 19.4% and 73.6%, respectively. • The median overall survival and median progression-free survival were 25.3 and 7.9 months, respectively. • Safety profile was consistent with those previously reported, with hand-foot skin reaction (58.0%), lipase elevation (57.3%) and diarrhoea (42.7%) as the most frequently observed drug-related adverse events. Neither unknown adverse event nor cumulative toxicity was observed over the long-term use of sorafenib. • Despite the dose discontinuation/interruption/reduction, the mean and median relative dose intensities were 86.4% and 97.4%, respectively.
• The final results of this trial showed that long-term use of sorafenib after cytokine treatment was well tolerated and provided new efficacy data, including late-response events and favourable overall survival in Japanese patients with metastatic RCC.
• 在一项 II 期试验中探索索拉非尼在日本转移性肾细胞癌（RCC）患者中的长期疗效和安全性。
• 共有 131 名接受过肾切除术且至少接受过一种细胞因子治疗失败的转移性 RCC 日本患者接受了每日两次 400mg 索拉非尼的连续治疗，并对这些患者的疗效和安全性参数进行了评估，包括客观缓解率、无进展生存期和总生存期。
• 共有 129 名患者可进行意向治疗分析，131 名患者可进行安全性分析。
• 25 名患者（19.4%）有确认的部分缓解，87 名患者（67.4%）有最佳总体缓解的稳定疾病。25 名患者中包括 6 名晚反应者，他们在稳定疾病 9.2 个月或更长时间后才出现缓解。客观缓解率和疾病控制率分别为 19.4%和 73.6%。
• 中位总生存期和中位无进展生存期分别为 25.3 个月和 7.9 个月。
• 安全性特征与之前报道的一致，最常见的药物相关不良反应为手足皮肤反应（58.0%）、脂肪酶升高（57.3%）和腹泻（42.7%）。在长期使用索拉非尼期间，未观察到未知的不良反应或累积毒性。
• 尽管有剂量中断/中断/减少，但平均和中位相对剂量强度分别为 86.4%和 97.4%。
• 该试验的最终结果表明，在细胞因子治疗后长期使用索拉非尼耐受性良好，并提供了新的疗效数据，包括日本转移性 RCC 患者的晚反应事件和有利的总生存期。
