基于 SPIRITS 和 G-SOX 试验数据评估基于肾功能的 S-1 剂量公式的临床有效性。
Evaluation of clinical validity of an S-1 dosage formula based on renal function using data of the SPIRITS and the G-SOX trials.
机构信息
Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan.
出版信息
Gastric Cancer. 2022 Jul;25(4):770-782. doi: 10.1007/s10120-022-01291-z. Epub 2022 Mar 31.
BACKGROUND
The aim of this study was to evaluate clinical validity of the S-1 dosage formula based on body surface area (BSA) and creatinine clearance (CLcr) to achieve the target area under the concentration-time curve of 5-FU, which we had developed and refined in each prospective pharmacokinetic study.
METHODS
The recommended dose determined by the refined formula was assessed using data of the SPIRITS (S-1 vs. S-1 plus cisplatin [SP]) and the G-SOX (SP vs. S-1 plus oxaliplatin [SOX]) trials. Nine hundred and thirty-eight patients in these trials were classified into three groups according to their actual S-1 starting doses compared with the recommended doses (under-dosed, <recommended dose; equal-dosed, =recommended dose; over-dosed, >recommended dose).
RESULTS
The patients in the under-dosed group in both trials showed similar tendencies: male, younger, higher BSA, and higher CLcr. The incidence of any grade neutropenia was significantly greater in the over-dosed group compared with the equal-dosed group in the S-1 and the SOX arms. The hazard ratios (HR) of overall survival (OS) (under-dosed vs. equal-dosed) were 1.361 (S-1 arm), 1.259 (SP arm) in the SPIRITS trial, and 1.381 (SOX arm), 0.999 (SP arm) in the G-SOX trial. Multivariate analysis in all the patients demonstrated that OS of the over-dosed group was equivalent (HR 1.002, 95% confidence interval [CI] 0.850-1.182, p = 0.980) and that of the under-dosed group was inferior (HR 1.267, 95% CI 1.005-1.597, p = 0.045) to the equal-dosed group.
CONCLUSIONS
It is suggested that the refined S-1 dosage formula can recommend optimal dose in terms of safety and efficacy.
背景
本研究旨在评估基于体表面积（BSA）和肌酐清除率（CLcr）的 S-1 剂量公式的临床有效性，以达到我们在每个前瞻性药代动力学研究中开发和完善的 5-FU 浓度-时间曲线下面积的目标。
方法
使用 SPIRITS（S-1 与 S-1 联合顺铂[SP]）和 G-SOX（S-1 与 S-1 联合奥沙利铂[SOX]）试验的数据评估通过改良公式确定的推荐剂量。根据实际 S-1 起始剂量与推荐剂量的比较（剂量不足，<推荐剂量；剂量相等，=推荐剂量；剂量过量，>推荐剂量），将这两项试验中的 938 例患者分为三组。
结果
两项试验中剂量不足组的患者均表现出相似的趋势：男性、年龄较小、BSA 较高、CLcr 较高。与剂量相等组相比，S-1 和 SOX 臂中过量组的任何级别中性粒细胞减少症发生率显著更高。SPIRITS 试验中，总生存期（OS）的风险比（HR）（剂量不足组与剂量相等组）为 1.361（S-1 臂）、1.259（SP 臂），而 G-SOX 试验中为 1.381（SOX 臂）、0.999（SP 臂）。所有患者的多变量分析表明，过量组的 OS 相当（HR 1.002，95%置信区间[CI]0.850-1.182，p=0.980），而剂量不足组的 OS 较差（HR 1.267，95%CI 1.005-1.597，p=0.045）。
结论
建议改良后的 S-1 剂量公式可以根据安全性和疗效推荐最佳剂量。
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