Phase I and pharmacokinetic study of S-1 combined with weekly paclitaxel in patients with advanced gastric cancer.
OBJECTIVE
A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer.


METHODS
Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m(2), depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD.


RESULTS
The MTD of paclitaxel was presumed to be 60 mg/m(2), because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m(2). Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m(2).


CONCLUSIONS
Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m(2). This regimen could represent a novel and low toxic combination for advanced gastric cancer.
Fujitani
Kazumasa
K
Department of Surgery, Osaka National Hospital, Japan. fujitani@onh.go.jp
Narahara
Hiroyuki
H
Takiuchi
Hiroya
H
Tsujinaka
Toshimasa
T
Satomi
Eriko
E
Gotoh
Masahiro
M
Hirao
Motohiro
M
Furukawa
Hiroshi
H
Taguchi
Tetsuo
T
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012306:Risk; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors; D016896:Treatment Outcome
D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel