Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Clin Oncol. 2010 Dec 1;28(34):5022-9. doi: 10.1200/JCO.2010.29.1203. Epub 2010 Oct 25.
This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU).
Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy.
A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006).
S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.
本Ⅱ期多中心试验旨在评估 S-1 治疗日本转移性肾细胞癌（mRCC）患者的疗效和安全性。我们还研究了肿瘤中参与氟尿嘧啶（FU）代谢的酶的 mRNA 表达水平与反应之间的关系。
对接受过肾切除术且细胞因子为基础的免疫治疗无效或禁忌的 mRCC 患者进行研究。S-1 按照体表面积口服给药，剂量为 80、100 或 120mg/天，每日 1 至 28 天，每 42 天为一个周期。主要终点是客观缓解率。采用逆转录-聚合酶链反应（RT-PCR）检测肿瘤组织中与 FU 相关的酶的 mRNA 表达水平，标本取自肾切除术时获得的福尔马林固定、石蜡包埋组织。
共纳入 45 例符合条件的患者。45 例患者中，11 例（24.4%）对 S-1 有部分缓解，28 例（62.2%）疾病稳定。中位无进展生存期为 9.2 个月。大多数不良事件的严重程度为轻度至中度。最常见的 3/4 级药物相关不良事件为中性粒细胞减少（8.9%）和厌食（8.9%）。治疗反应患者的胸苷酸合成酶（TS）mRNA 表达水平明显较低（t 检验，P =.048），且 TS mRNA 表达水平低于中位数的患者无进展生存期明显长于表达水平较高的患者（对数秩检验，P =.006）。
S-1 对细胞因子难治性 mRCC 有效。治疗前肿瘤中 TS mRNA 水平的定量分析可能有助于预测 mRCC 对 S-1 的反应。
