title: Phase I study of the sequential administration of S-1 and cisplatin for metastatic gastric cancer.
abstract: The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been reported to be active against metastatic gastric cancer (MGC) and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. The sequential combination of S-1 (tegafur, oxonic acid, 5-chloro-2,4-dihydroxypyridine) followed by CDDP for MGC was investigated. A phase I trial applying increasing doses of oral administration of S-1 (65-80 mg/m(2)) for 21 days and increasing doses of CDDP (60-80 mg/m(2)) on day 22 every 35 days was conducted in order to determine the maximum tolerated dose (MTD) and recommended phase II dose. Patients with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, ECOG performance status less than 3 and adequate organ functions were eligible for the study. Three patients were treated at each dose level with escalation based on toxicity. Fifteen patients were included and evaluated for dose-limiting toxicity (DLT) and MTD. DLT included NCICTC grade 3 anorexia and fatigue in patients treated at S-1 80 mg/m(2) and CDDP 80 mg/m(2) (dose level 5). The other toxicities, grade 3 or higher, included neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. Therefore, the recommended dose was a combination of S-1 at 80 mg/m(2) and CDDP at 70 mg/m(2). This sequential administration of S-1 and CDDP every 35 days is tolerable and warrants a phase II trial. A multicenter phase II study is currently under way.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan. e-baba@intmed1.med.kyushu-u.ac.jp
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Fujishima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusaba
authors.forename: Taito
authors.initials: T
authors.lastname: Esaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ariyama
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Risa
authors.initials: R
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Mitsugi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakano
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D010094:Oxonic Acid / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin