A phase I study of paclitaxel, cisplatin, and fluorouracil (TCF) for advanced gastric cancer.
OBJECTIVE
A phase I study of TCF therapy, which consists of paclitaxel (TXL: Taxol) + cisplatin (CDDP) + 5-fluorouracil (5-FU), in advanced gastric cancer patients was performed to determine the recommended dose (RD) for a phase II study by checking the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of 5-FU above the fixed dose of TXL and CDDP.


METHODS
The doses of TXL and CDDP were fixed at 80 and 25 mg/m(2), respectively, while that of 5-FU was increased by 100 mg/m(2 )in each cohort from 300 mg/m(2) (level 1) to a maximum of 600 mg/m(2) (level 4). One cycle consisted of administration of these agents once per week for 3 weeks, every 4 weeks.


RESULTS
A total of twelve eligible patients were included in this study. At level 1, two of three cases showed grade 3 leukopenia. At level 2, one of three cases showed grade 4 neutropenia (recovered within 3 days), and another one case showed grade 3 neutropenia. At level 3, one of three cases showed grade 3 neutropenia, and at level 4, one of three cases showed grade 4 neutropenia (recovered within 3 days), with grade 3 neutropenia in the other two cases. Even at the highest dose administered, none of the patients showed DLT. Moreover, no non-hematological toxicity judged to be DLT was observed through all levels. Six of the twelve patients had measurable disease, and the overall response rate was 83%.


CONCLUSIONS
Although the MTD level was not determined, based on the observed efficacy and the results of other clinical trials, the recommended doses of TXL, CDDP, and 5-FU for the TCF regimen were set as 80, 25, and 600 mg/m(2), respectively, and a phase II study to investigate the clinical effectiveness and safety of this regimen has now begun.
Hara
Takuo
T
Department of Surgery, Kouseiren Takaoka Hospital, Takaoka, Toyama 933-8555, Japan. 02026hara@kouseiren-ta.or.jp
Omura
Kenji
K
Hirano
Makoto
M
Asada
Yasuyuki
Y
Munemoto
Yoshinori
Y
Sakamoto
Junichi
J
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil