Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors.
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.
Overman
Michael J
MJ
University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA. moverman@mdanderson.org
Kopetz
Scott
S
Varadhachary
Gauri
G
Fukushima
Masakazu
M
Kuwata
Keizo
K
Mita
Akira
A
Wolff
Robert A
RA
Hoff
Paulo
P
Xiong
Henry
H
Abbruzzese
James L
JL
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
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine