*Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Jpn J Clin Oncol. 2014 Feb;44(2):122-6. doi: 10.1093/jjco/hyt185. Epub 2013 Dec 1.
A planned primary analysis of a Phase II study of S-1 demonstrated that the drug was active and tolerable in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. Furthermore, pharmacogenomic analysis suggested that low expression of thymidylate synthase mRNA may have been associated with clinical outcome in terms of overall response rate and progression-free survival. Here, we report the results of the final analysis assessing the efficacy and safety of S-1 including overall survival.
Patients with renal cell carcinoma were eligible if they had had at least one regimen of cytokine for metastatic disease. S-1 was orally administered on Days 1-28 of a 42-day cycle until disease progression. The primary endpoint was the overall response rate, and the secondary endpoint included progression-free survival, overall survival and safety.
A total of 45 patients were treated with S-1 and were fully assessable for efficacy and safety. At the final analysis, a response was seen in 11 patients (overall response rate, 24.4%; 95% confidence interval: 12.9-39.5%), including two patients who achieved a complete response. The final median progression-free and overall survival were 9.2 and 42.8 months, respectively. The safety profile of S-1 was favorable. It was suggested that there was no relation between overall survival and the expression level of thymidylate synthase.
This final analysis confirms that S-1 treatment is effective and safe in patients with cytokine-refractory renal cell carcinoma.
S-1 二期研究的计划主要分析表明，该药在接受细胞因子治疗后疾病进展的日本转移性肾细胞癌患者中具有活性和可耐受性。此外，药物基因组学分析表明，胸苷酸合成酶 mRNA 低表达可能与总缓解率和无进展生存期的临床结局相关。在此，我们报告了评估 S-1 疗效和安全性（包括总生存期）的最终分析结果。
患有肾细胞癌的患者如果至少有一种细胞因子用于转移性疾病的治疗方案，则符合条件。S-1 于每 42 天周期的第 1-28 天口服给药，直至疾病进展。主要终点是总缓解率，次要终点包括无进展生存期、总生存期和安全性。
共有 45 名患者接受了 S-1 治疗，疗效和安全性均完全可评估。在最终分析时，11 名患者（总缓解率为 24.4%；95%置信区间：12.9-39.5%）观察到缓解，包括 2 名完全缓解的患者。最终的中位无进展生存期和总生存期分别为 9.2 个月和 42.8 个月。S-1 的安全性特征良好。无证据表明总生存期与胸苷酸合成酶的表达水平之间存在关系。
该最终分析证实，S-1 治疗细胞因子难治性肾细胞癌患者是有效且安全的。
