A phase I study of S-1 administration and a 24-h infusion of cisplatin plus paclitaxel in patients with advanced gastric cancer.
OBJECTIVE
The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD) and the preliminary antitumor activity of S-1, oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimide, in combination with cisplatin and paclitaxel for advanced gastric cancer.


METHODS
Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1 and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160 and 180 mg/m2).


RESULTS
Twenty patients were enrolled. The toxicities were generally mild no grade 4 hematological toxicity or grade 3 non-hematological toxicity were observed. Level 4 was considered as the MTD because of a treatment delay of more than 2 weeks in 3 out of 6 patients. The RD of paclitaxcel was 160 mg/m2. The overall response rate was 75%.


CONCLUSIONS
A triple combination chemotherapy consisting of S-1, cisplatin and paclitaxel showed a tolerable level of adverse reactions and favorable antitumor activity.
Iwase
Hiroaki
H
Department of Gastroenterology, National Organization, Nagoya Medical Center, 4-1-1 Sannomaru Naka-ku, Nagoya 460-0001, Japan. iwaseh@nnh.hosp.go.jp
Shimada
Masaaki
M
Tsuzuki
Tomoyuki
T
Okeya
Masayuki
M
Kobayashi
Keiko
K
Hibino
Yuichi
Y
Watanabe
Hisanori
H
Goto
Hidemi
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel; D002945:Cisplatin