TAS-102 in gastric cancer: Development and perspectives of a new biochemically modulated fluroropyrimidine drug combination

Giandomenico Roviello; Sara Fancelli; Marta Rita Gatta Michelet; Giuseppe Aprile; Stefania Nobili; Franco Roviello; Fabio Cianchi; Enrico Mini; Daniele Lavacchi

doi:10.1016/j.critrevonc.2020.102987

TAS-102 in gastric cancer: Development and perspectives of a new biochemically modulated fluroropyrimidine drug combination

Crit Rev Oncol Hematol. 2020 Aug:152:102987. doi: 10.1016/j.critrevonc.2020.102987. Epub 2020 May 21.

Authors

Giandomenico Roviello¹, Sara Fancelli², Marta Rita Gatta Michelet², Giuseppe Aprile³, Stefania Nobili⁴, Franco Roviello⁵, Fabio Cianchi⁶, Enrico Mini⁴, Daniele Lavacchi²

Affiliations

¹ Department of Health Sciences, University of Florence, viale Pieraccini, 6, 50139, Florence, Italy. Electronic address: giandomenicoroviello@hotmail.it.
² School of Human Health Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.
³ Department of Oncology, San Bortolo General Hospital, Vicenza, Italy.
⁴ Department of Health Sciences, University of Florence, viale Pieraccini, 6, 50139, Florence, Italy.
⁵ Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Viale Bracci - Policlinico "Le Scotte", 53100, Siena, Italy.
⁶ Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

PMID: 32485527
DOI: 10.1016/j.critrevonc.2020.102987

Abstract

TAS-102 is a preconstituted drug combination comprising an oral fluoropyrimidine (trifluridine, TFT) and a potent inhibitor of thymidine phosphorylase (tipiracil hydrochloride, TPI). TFT/TPI has recently received Food and Drug Administration (FDA) approval also for the treatment of gastric cancer after at least two lines of chemotherapy. The approval was based on a large phase 3 trial (TAGS), in which TAS-102 showed a 31 % decrease in the risk of death compared with placebo. Here, we review the pharmacological properties, clinical development and potential future directions of TAS-102 in gastric cancer.

Keywords: Chemotherapy; Gastric cancer; TAS-102; Third line.

Publication types

Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Biochemical Phenomena
Drug Combinations
Humans
Pyrrolidines / therapeutic use*
Stomach Neoplasms* / drug therapy
Thymine
Trifluridine / therapeutic use*
Uracil / analogs & derivatives*
Uracil / therapeutic use

Substances

Drug Combinations
Pyrrolidines
trifluridine tipiracil drug combination
Uracil
Thymine
Trifluridine