PURPOSE: Trifluridine/tipiracil (FTD/TPI) is approved for advanced colorectal and gastric/gastroesophageal cancer; however, data in patients with renal impairment (RI) are limited. This phase I study evaluated FTD/TPI in patients with advanced solid tumors and varying degrees of RI to develop dosing guidance. METHODS: Patients were enrolled into normal renal function (CrCl ≥ 90 mL/min), mild RI (CrCl 60-89 mL/min), or moderate RI (CrCl 30-59 mL/min) cohorts and administered the recommended FTD/TPI dose (35 mg/m2 twice daily, days 1-5 and 8-12; 28-day cycle). Based on interim pharmacokinetics/safety data, patients with severe RI (CrCl 15-29 mL/min) were enrolled and received FTD/TPI 20 mg/m2 twice daily. RESULTS: Forty-three patients (normal renal function [n = 12]; mild RI [n = 12]; moderate RI [n = 11]; severe RI [n = 8]) were enrolled and treated. At steady state, compared to values in patients with normal renal function, FTD area under the curve (AUC) was not significantly different in patients with RI, but TPI AUC was significantly higher and increased with RI severity. FTD/TPI safety profile was consistent with prior experience, but grade ≥ 3 adverse events (AEs) were more frequent in the RI cohorts (83.3% [mild], 90.9% [moderate], 75.0% [severe], and normal [50.0%]). Hematologic AEs (anemia and neutropenia) were more frequent with RI. Overall, seven patients discontinued because of unrelated, nonhematologic AEs. CONCLUSION: FTD/TPI is safe and tolerable at the recommended 35 mg/m2 dose in patients with mild/moderate RI and at the reduced 20 mg/m2 dose in patients with severe RI. TRIAL REGISTRATION: NCT02301117, registration date: November 21, 2014.

City of Hope Comprehensive Cancer Center Duarte CA USA

Cleveland Clinic Cleveland OH USA

Division of Hematology Oncology University of California Los Angeles CA USA

Division of Oncology University of Kansas Medical Center Kansas City KS USA

Fakultni Nemocnice u Sv Anny v Brně Anesteziologicko Resustitační Klinika Brno Czech Republic

Institute for Pulmonary Diseases of Vojvodina University of Novi Sad Novi Sad Serbia

Medical Oncology Northwell Health Cancer Institute 1111 Marcus Avenue Suite 216 Lake Success NY 11042 USA

Oncology Institute of Vojvodina University of Novi Sad Novi Sad Serbia

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD USA

Taiho Oncology Inc Princeton NJ USA

Texas Oncology Baylor University Medical Center Dallas TX USA

Thomayer Hospital Prague and Department of Biophysics and Informatics 1st Medical Faculty Prague Czech Republic

University of Florida Health Cancer Center Gainesville FL USA

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