Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik, Langenbeckstrasse 1, 55131 Mainz, Germany.
Universitätsklinikum Hamburg-Eppendorf, II. Medizinische Klinik und Poliklinik, Martinistr. 52, 20246 Hamburg, Germany.
Future Oncol. 2021 Sep;17(25):3309-3319. doi: 10.2217/fon-2021-0278. Epub 2021 May 17.
To determine a recommended Phase II dose of the oral fluoropyrimidine trifluridine/tipiracil (FTD/TPI) combined with the multi-kinase inhibitor regorafenib (REG) in refractory metastatic colorectal cancer patients. A conventional 3 + 3 dose finding design was used. FTD/TPI was administered on days 1-5 and 8-12 of a 28-day cycle, REG on days 2-22. Two dose levels were used: FTD/TPI 25 mg/m b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m b.i.d. + REG 120 mg/d. In total, 12 patients were treated at two dose levels. Three dose-limiting toxicities were observed; all were grade 3 hypertension causally attributed to REG. Recommended Phase II dose is FTD/TPI 25 mg/m b.i.d. + REG 120 mg/d. Median progression-free survival was 3.81 months (95% CI: 1.51-5.29), median OS 11.1 months (95% CI: 2.3-18.2). The combination of REG and FTD/TPI is feasible and safe. Efficacy signals exceed that of the single agents at acceptable toxicity levels and are clinically meaningful.
为了确定口服氟嘧啶三氟尿苷/替匹嘧啶（FTD/TPI）联合多激酶抑制剂瑞戈非尼（REG）在难治性转移性结直肠癌患者中的 II 期推荐剂量。采用常规的 3+3 剂量递增设计。FTD/TPI 在 28 天周期的第 1-5 天和第 8-12 天给药，REG 在第 2-22 天给药。使用了两个剂量水平：FTD/TPI 25mg/m 每日两次+REG 120mg/d，然后递增至 FTD/TPI 35mg/m 每日两次+REG 120mg/d。总共治疗了 12 名患者，在两个剂量水平上。观察到三例剂量限制性毒性；均为 3 级高血压，与 REG 因果相关。推荐的 II 期剂量为 FTD/TPI 25mg/m 每日两次+REG 120mg/d。中位无进展生存期为 3.81 个月（95%CI：1.51-5.29），中位总生存期为 11.1 个月（95%CI：2.3-18.2）。REG 和 FTD/TPI 的联合是可行和安全的。疗效信号超过了单药治疗，且毒性可接受，具有临床意义。
