A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer

6533b858fe1ef96bd12b6d1b

RESEARCH PRODUCT

A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer

Alexander Stein Maurice Michel Jens U. Marquardt Helge Schroeder Oliver Waidmann Marcus-alexander Woerns Arndt Weinmann Markus Moehler Martin Maenz Joseph Tintelnot Friedrich Foerster Joerg Trojan

subject

Adult Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Pyrrolidines Maximum Tolerated Dose Pyridines Colorectal cancer Administration Oral Trifluridine Drug Administration Schedule Trifluridine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Refractory Regorafenib Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Dose escalation Humans Response Evaluation Criteria in Solid Tumors Aged Tipiracil Dose-Response Relationship Drug business.industry Phenylurea Compounds General Medicine Middle Aged medicine.disease Progression-Free Survival Drug Combinations 030104 developmental biology Oncology chemistry Third line Drug Resistance Neoplasm 030220 oncology & carcinogenesis Hypertension Toxicity Feasibility Studies Female Colorectal Neoplasms business Thymine medicine.drug

description

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.

year	journal	country	edition	language
2021-09-01	Future Oncology

https://doi.org/10.2217/fon-2021-0278