Abstract
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.
Publication types
-
Clinical Trial
-
Clinical Trial, Phase I
-
English Abstract
-
Multicenter Study
MeSH terms
-
Administration, Oral
-
Adolescent
-
Adult
-
Aged
-
Anorexia / chemically induced
-
Antineoplastic Agents / administration & dosage*
-
Antineoplastic Agents / adverse effects
-
Antineoplastic Agents / pharmacokinetics
-
Breast Neoplasms / drug therapy
-
Breast Neoplasms / metabolism
-
Colonic Neoplasms / drug therapy
-
Colonic Neoplasms / metabolism
-
Drug Administration Schedule
-
Female
-
Fluorodeoxyuridylate / administration & dosage
-
Fluorodeoxyuridylate / adverse effects
-
Fluorodeoxyuridylate / analogs & derivatives*
-
Fluorodeoxyuridylate / pharmacokinetics
-
Humans
-
Lung Neoplasms / drug therapy
-
Lung Neoplasms / metabolism
-
Male
-
Middle Aged
-
Neoplasms / drug therapy*
-
Neoplasms / metabolism
-
Pancreatic Neoplasms / drug therapy
-
Pancreatic Neoplasms / metabolism
-
Stomach Neoplasms / drug therapy
-
Stomach Neoplasms / metabolism
Substances
-
Antineoplastic Agents
-
Fluorodeoxyuridylate
-
tetradecyl 2'-deoxy-5-fluoro-5'-uridylate