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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
MW. Saif, CR. Becerra, MG. Fakih, W. Sun, L. Popovic, S. Krishnamurthi, TJ. George, MA. Rudek, DR. Shepard, J. Skopek, V. Sramek, B. Zaric, I. Yamamiya, KA. Benhadji, K. Hamada, Y. He, L. Rosen
Language English Country Germany
Document type Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 1997-02-01 to 1 year ago
Medline Complete (EBSCOhost)
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-02-01 to 1 year ago
Public Health Database (ProQuest)
from 1997-02-01 to 1 year ago
- MeSH
- Anemia chemically induced epidemiology MeSH
- Adult MeSH
- Drug Combinations MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasms drug therapy MeSH
- Kidney Diseases physiopathology MeSH
- Neutropenia chemically induced epidemiology MeSH
- Area Under Curve MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects pharmacokinetics MeSH
- Pyrrolidines administration & dosage adverse effects pharmacokinetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Severity of Illness Index MeSH
- Thymine administration & dosage adverse effects pharmacokinetics MeSH
- Trifluridine administration & dosage adverse effects pharmacokinetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Research Support, Non-U.S. Gov't MeSH
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
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
University of Florida Health Cancer Center Gainesville FL USA
References provided by Crossref.org
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- $a Saif, Muhammad Wasif $u Medical Oncology, Northwell Health Cancer Institute, 1111 Marcus Avenue, Suite 216, Lake Success, NY, 11042, USA. wsaif@northwell.edu
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