title: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors.
abstract: TAS-102 is a novel formulation of the fluorinated pyrimidine analogue trifluorothymidine (FTD) with an inhibitor of thymidine phosphorylase. The purpose of this study was to determine the MTD and DLT for TAS-102 administered three times a day on days 1-5 and 8-12 every 4 weeks. Fifteen patients were enrolled with two patients experiencing dose-limiting fatigue and granulocytopenia at the first dose level (80 mg/m2/day). Granulocytopenia was the primary toxicity: 7 patients experienced grade 3 or 4 granulocytopenia with the first course. No responses were noted, but nine patients demonstrated prolonged stable disease in this heavily pretreated 5-FU refractory population.
authors.affiliation: University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA. moverman@mdanderson.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.forename: Gauri
authors.initials: G
authors.lastname: Varadhachary
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukushima
authors.forename: Keizo
authors.initials: K
authors.lastname: Kuwata
authors.forename: Akira
authors.initials: A
authors.lastname: Mita
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: Paulo
authors.initials: P
authors.lastname: Hoff
authors.forename: Henry
authors.initials: H
authors.lastname: Xiong
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011759:Pyrrolidines; D013941:Thymine; D014271:Trifluridine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine