Abstract
Aim: 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. Materials & methods: 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/m2 b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m2 b.i.d. + REG 120 mg/d. Results: 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/m2 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). Conclusion: 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.
| Original language | English |
|---|---|
| Journal | Future Oncology |
| Volume | 17 |
| Issue number | 25 |
| Pages (from-to) | 3309-3319 |
| Number of pages | 11 |
| ISSN | 1479-6694 |
| DOIs | |
| Publication status | Published - 09.2021 |
Funding
The study was supported by a grant from B Vital GmbH. M Michel was supported by the Clinician Scientist Fellowship ‘Else Kröner Research College: 2018 Kolleg.05’. M Moehler reports a scientific grant from Bayer for his institution personal fees, as well honoraria and travel support by Bayer, Taiho and Servier. A Stein received institutional research funding and honoraria for advisory boards or lectures from Servier. J Trojan received honoraria for talks and advisory board role from Bayer and Servier. J Marquardt received honoraria and/or travel expenses from Bayer. O Waidmann received honoraria for advisory boards from Servier and Bayer, and honoraria for lectures from Bayer. M-A Woerns received honoraria and/or travel expenses from Bayer. F Foerster collaborates with Bayer in scientific pursuits. M Michel, J Tintelnot, A Weinmann, H Schroeder and M Maenz declare no conflict of interest.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
