title: [Antitumor Molecular Mechanism of Trifluridine and Tipiracil Hydrochloride (TAS-102: TFTD)].
abstract: Treatment options for patients with metastatic colorectal cancer (mCRC), who are refractory to standard chemotherapy, are limited. In a global multicenter randomized double-blind phase III study (RECOURSE study), TAS-102 (TFTD) administration significantly improved overall survival rate with favorable safety profile in mCRC patients refractory to standard chemotherapy (HR=0.68, p<0.001). TFTD was approved initially in Japan in March 2014 and is currently under review by health authorities in the United States and Europe. TFTD is expected to play an important role in salvage-line treatment for patients with mCRC. In this review, we present the history of its clinical development and the experimental data that elucidate the underlying molecular mechanism of action of TFTD and its key component, trifluridine.
authors.affiliation: Dept. of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Iimori
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D004338:Drug Combinations; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D011759:Pyrrolidines; D013941:Thymine; D014271:Trifluridine / Q000378:metabolism / Q000627:therapeutic use*; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D004247:DNA; D013941:Thymine; D014271:Trifluridine