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.
Keywords:
TAS-102; antiangiogenesis; colorectal cancer; fluoropyrimidine resistance; fluoropyrimidines; trifluorothymidine.
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology
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Angiogenesis Inhibitors / therapeutic use
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Antimetabolites, Antineoplastic / chemistry
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Antimetabolites, Antineoplastic / pharmacology*
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Antimetabolites, Antineoplastic / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Cycle / drug effects
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Clinical Trials as Topic
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Colorectal Neoplasms / drug therapy
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Colorectal Neoplasms / pathology
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Drug Combinations
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Drug Resistance, Neoplasm
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Fluorouracil / pharmacology
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Fluorouracil / therapeutic use
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Humans
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Pyrrolidines
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Thymine
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Treatment Outcome
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Trifluridine / chemistry
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Trifluridine / pharmacology*
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Trifluridine / therapeutic use*
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Uracil / analogs & derivatives*
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Uracil / chemistry
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Uracil / pharmacology
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Uracil / therapeutic use
Substances
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Angiogenesis Inhibitors
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Antimetabolites, Antineoplastic
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Drug Combinations
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Pyrrolidines
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trifluridine tipiracil drug combination
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Uracil
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Thymine
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Trifluridine
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Fluorouracil