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
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F21%3AN0000050" target="_blank" >RIV/00064190:_____/21:N0000050 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/21:00074690
Result on the web
<a href="http://dx.doi.org/10.1007/s00280-021-04308-z" target="_blank" >http://dx.doi.org/10.1007/s00280-021-04308-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00280-021-04308-z" target="_blank" >10.1007/s00280-021-04308-z</a>
Alternative languages
Result language
angličtina
Original language name
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
Original language description
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/m(2) 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/m(2) 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/m(2) dose in patients with mild/moderate RI and at the reduced 20 mg/m(2) dose in patients with severe RI.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
CANCER CHEMOTHERAPY AND PHARMACOLOGY
ISSN
0344-5704
e-ISSN
1432-0843
Volume of the periodical
88
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
485-497
UT code for WoS article
000658699100001
EID of the result in the Scopus database
2-s2.0-85107544296