title: TAS-102: a novel antimetabolite for the 21st century.
abstract: TAS-102, a novel antimetabolite combination chemotherapy agent, consists of a rediscovered antimetabolite agent, trifluorothymidine (trifluridine) combined with the metabolic inhibitor of thymidine phosphorylase, tipiracil, in a 1:0.5 molar ratio. Mechanism of action studies suggest that this agent works by incorporation into DNA. Both preclinical and clinical studies demonstrate that this agent is noncross-resistant with 5-fluorouracil. Tipiracil may also have antiangiogenic effects through inhibition of thymidine phosphorylase. Recent randomized Phase II and III trials demonstrate clinical activity (improved progression-free survival, time to decrease in performance status, prolonged overall survival) in metastatic colorectal cancer refractory to all standard agents. Monotherapy with TAS-102 has now been approved for this indication in Japan and in the USA.
authors.affiliation: University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Uboha
authors.affiliation: The Yale Cancer Center, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011759:Pyrrolidines; D013941:Thymine; D016896:Treatment Outcome; D014271:Trifluridine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine; D005472:Fluorouracil
keywords: TAS-102; antiangiogenesis; colorectal cancer; fluoropyrimidine resistance; fluoropyrimidines; trifluorothymidine