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A phase I, open-label study evaluating the safety and pharmacokinetics of trifluridine/tipiracil in patients with advanced solid tumors and varying degrees of renal impairment
- Source :
- Cancer Chemotherapy and Pharmacology. 88:485-497
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- 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. 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. 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. 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. NCT02301117, registration date: November 21, 2014.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Anemia
Trifluridine
Neutropenia
Toxicology
Gastroenterology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pharmacokinetics
Internal medicine
parasitic diseases
medicine
Pharmacology (medical)
Dosing
Adverse effect
Tipiracil
Pharmacology
business.industry
Area under the curve
medicine.disease
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
business
medicine.drug
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi...........4248748f5db1a31dcf2ea0b45dc04d2c