Open AccessA Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer
Author(s) -
Markus Moehler,
Maurice Stephan Michel,
Alexander Stein,
Joerg Trojan,
Jens U. Marquardt,
Joseph Tintelnot,
Oliver Waidmann,
Arndt Weinmann,
Marcus-Alexander Woerns,
H. Schroeder,
Martin Maenz,
Friedrich Foerster
Publication year - 2021
Publication title -
future oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.857
H-Index - 72
eISSN - 1744-8301
pISSN - 1479-6694
DOI - 10.2217/fon-2021-0278
Subject(s) - medicine , regorafenib , colorectal cancer , refractory (planetary science) , phases of clinical research , toxicity , gastroenterology , cancer , oncology , physics , astrobiology
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/m 2 b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m 2 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/m 2 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.