Overall survival and good tolerability of long-term use of sorafenib after cytokine treatment: final results of a phase II trial of sorafenib in Japanese patients with metastatic renal cell carcinoma
Overall survival and good tolerability of long-term use of sorafenib after cytokine treatment: final results of a phase II trial of sorafenib in Japanese patients with metastatic renal cell carcinoma
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DOI：
10.1111/j.1464-410x.2011.10281.x
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发表时间：
2011-12-01
影响因子：
4.5
通讯作者：
Akaza, Hideyuki
中科院分区：
文献类型：
--
作者：
Naito, Seiji;Tsukamoto, Taiji;Akaza, Hideyuki
目的探讨索拉非尼在日本转移性肾细胞癌(RCC)II期试验中的长期疗效和安全性。方法和方法131例接受过至少一种细胞因子系统治疗失败的日本转移性肾癌患者，接受索拉非尼400 mg的持续每日2次治疗，并对其疗效和安全性参数进行评估，包括客观有效率、无进展生存期和总生存期。129例患者有效用于意向治疗分析，131例患者有效用于安全性分析，25例(19.4%)患者确认部分缓解，87例(67.4%)患者病情稳定为最佳总体反应。这25名患者包括6名晚期应答者，他们在病情稳定9.2个月或更长时间后取得了反应。客观有效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，安全性与文献报道一致，最常见的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的过程中，没有观察到未知的不良事件和累积毒性。尽管剂量停止/中断/减少，但平均和中位相对剂量强度分别为86.4%和97.4%。结论本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具有良好的耐受性，并为日本转移性肾癌患者提供了新的疗效数据，包括晚期反应事件和有利的总体生存。
OBJECTIVETo explore the long-term efficacy and safety of sorafenib in Japanese patients with metastatic renal cell carcinoma (RCC) in a phase II trial.PATIENTS AND METHODSIn 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.RESULTSOf 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.CONCLUSIONThe 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.