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01-02-2020 | Colon Cancer | SHORT REPORT

Pharmacological effects of the simultaneous and sequential combinations of trifluridine/tipiracil (TAS-102) and 5-fluorouracil in fluoropyrimidine-sensitive colon cancer cells

Authors: Paola Orlandi, Daniela Gentile, Marta Banchi, Federico Cucchiara, Teresa Di Desidero, Chiara Cremolini, Roberto Moretto, Alfredo Falcone, Guido Bocci

Published in: Investigational New Drugs | Issue 1/2020

Summary

The aim of this study was to investigate possible synergistic effects in vitro of trifluridine/tipiracil (TAS-102) and 5-fluoruracil (5-FU) on fluoropyrimidine-sensitive colon cancer cell lines of different mutational status in order to build a rational basis for the future use of this combination therapy in adjuvant settings or as a first-line treatment for metastatic disease. Proliferation assays were performed on HT-29 (B-raf mutated), SW-620 (ras mutated), and Caco-2 (wild type) colon cancer cell lines exposed to 120-h treatments of 5-FU, TAS-102 and their different combination schedules (simultaneous, sequential and reverse) at equimolar and non-equimolar ratios. The synergistic, additive and antagonistic effects of 5-FU and TAS-102 were determined by the combination index (CI) and dose reduction index (DRI). Our preclinical in vitro results may suggest an apparently counterintuitive but strongly synergistic combination of 5-FU and TAS-102 in fluoropyrimidine-sensitive colon cancer cells allowing a marked theoretical reduction in the administered doses of both drugs. In particular, this association seems to be highly effective in wild-type colon cancer cells, both in sequential and simultaneous schedules. Together, these data may build a rational basis for the future use of TAS-102 combined with 5-FU in adjuvant settings, or as a first-line treatment for metastatic disease.

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Title: Pharmacological effects of the simultaneous and sequential combinations of trifluridine/tipiracil (TAS-102) and 5-fluorouracil in fluoropyrimidine-sensitive colon cancer cells
Authors: Paola Orlandi
Daniela Gentile
Marta Banchi
Federico Cucchiara
Teresa Di Desidero
Chiara Cremolini
Roberto Moretto
Alfredo Falcone
Guido Bocci
Publication date: 01-02-2020
Publisher: Springer US
Keywords: Colon Cancer
Colon Cancer
Published in: Investigational New Drugs / Issue 1/2020
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00804-5

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