[Phase I clinical study of TT-62. Research group of TT-62].
TT-62 is a new derivative of FdUMP, which is the active metabolite of 5-FU. A phase I clinical study of TT-62 was conducted by a cooperative study. The same patients received single and 2-week oral administration of TT-62. Starting from 60 mg/m2 (1n), the dose was escalated to 420 mg/m2 (7n). In the single administration, the maximum tolerated dose (MTD) could not be determined. In the 2-week administration, MTD was 420 mg/m2, and the dose limiting factor was gastro-intestinal disturbances such as anorexia, nausea, vomiting and diarrhea. Increases in GOT.GPT and a decrease in hemoglobin content were observed. After administration was stopped all side effects disappeared. TT-62 was detected mainly in the plasma, while trace amounts of 5-FU and FUdR were also detected. TT-62 was excreted mostly in the urine, as alpha-fluoro-beta-alanine (FBAL). The cumulative urinary excretion of FBAL was about 80% of the total dose, and the oral absorption of TT-62 was thus thought to be good.
Taguchi
T
T
Dept. of Surgery, Osaka University, Suita, Japan.
Furue
H
H
Niitani
H
H
Ohta
K
K
Tsukagoshi
S
S
Wakui
A
A
Hasegawa
K
K
Nakao
I
I
Ohashi
Y
Y
Tominaga
T
T
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005468:Fluorodeoxyuridylate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism
D000970:Antineoplastic Agents; D005468:Fluorodeoxyuridylate; C076837:tetradecyl 2'-deoxy-5-fluoro-5'-uridylate