[High-dose Tegafur (FT) for primary lung cancer: a phase I trial].
A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.
Matsui
K
K
Dept. of Internal Medicine, Osaka Prefectural Habikino Hospital.
Fukuoka
M
M
Masuda
N
N
Kusunoki
Y
Y
Negoro
S
S
Takada
M
M
Ryu
S
S
Sakai
N
N
Takifuji
S
S
Kudoh
S
S
D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005472:Fluorouracil / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D005641:Tegafur; D005472:Fluorouracil