Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan.
Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, 501-1196, Japan.
Cancer Chemother Pharmacol. 2019 Nov;84(5):987-992. doi: 10.1007/s00280-019-03935-x. Epub 2019 Sep 3.
BACKGROUND/AIM: Sunitinib is used for the treatment of metastatic renal cell carcinoma (mRCC). Asian patients, including Japanese, tend not to tolerate long-term sunitinib therapy of 50 mg p.o. once daily for 4 weeks, followed by 2 week off treatment due to severe adverse events at this dosage level. The aim of this retrospective study was to investigate the optimal dose of sunitinib for long-term continuation in Asian patients with mRCC.
The study cases were 50 patients with mRCC who were treated with sunitinib between June 2008 and December 2017. Risk analysis for "unacceptable" adverse events (depending on the physician, ranging from grade 2 to ≥ grade 3) leading to discontinuation of sunitinib was determined by time-dependent Cox proportional hazard regression analysis.
A total of 54 unacceptable adverse events leading to discontinuation occurred. Multivariable analysis indicated that a sunitinib dose of ≤ 37.5 mg/day significantly reduced the risk of discontinuation due to adverse events in comparison with 50 mg/day [hazard ratio (HR) 0.08, 95% confidence interval (CI) 0.03-0.21, p < 0.001). The progression-free survival (PFS) with a sunitinib dose ≤ 37.5 mg/day was longer than that associated with a dose of 50 mg/day, albeit not to a statistically significant degree (120 days for ≤ 37.5 mg/day vs 41 days for 50 mg/day, HR 0.39, 95% CI 0.10-1.44, p = 0.157).
Our findings suggest that the optimal dose of sunitinib for Asian, including Japanese, patients with mRCC is ≤ 37.5 mg/day.
背景/目的：舒尼替尼用于治疗转移性肾细胞癌（mRCC）。亚洲患者，包括日本人，由于在该剂量水平下严重不良反应，不能耐受舒尼替尼 50mg 口服，每天一次，持续 4 周，然后停药 2 周的长期治疗。本回顾性研究的目的是研究舒尼替尼在亚洲 mRCC 患者中的最佳剂量，以实现长期持续治疗。
本研究病例为 2008 年 6 月至 2017 年 12 月期间接受舒尼替尼治疗的 50 例 mRCC 患者。采用时间依赖性 Cox 比例风险回归分析确定导致舒尼替尼停药的“不可接受”不良事件（由医生决定，严重程度为 2 级至≥3 级）的风险分析。
共发生 54 例不可接受的不良事件导致停药。多变量分析表明，与 50mg/天相比，舒尼替尼剂量≤37.5mg/天显著降低了因不良反应而停药的风险[风险比（HR）0.08，95%置信区间（CI）0.03-0.21，p<0.001]。舒尼替尼剂量≤37.5mg/天的无进展生存期（PFS）长于 50mg/天，但差异无统计学意义（120 天≤37.5mg/天 vs 41 天 50mg/天，HR 0.39，95%CI 0.10-1.44，p=0.157）。
我们的研究结果表明，舒尼替尼治疗亚洲，包括日本，mRCC 患者的最佳剂量为≤37.5mg/天。
