title: Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer.
abstract: A phase I study of S-1 and biweekly docetaxel (DOC) combination therapy was conducted to determine the maximum tolerated dose (MTD) and pharmacokinetic parameters. Fourteen patients with advanced or recurrent gastric cancer were analyzed. The treatment consisted of S-1 [body surface area (BSA) <1.25 m2:80 mg/day, 1.25<or= BSA <1.50 m2: 100 mg/day, 1.50 m2<or= BSA; 120 mg/day, orally, day 1-14) and DOC (30-40 mg/m2/day, intravenously, day 1 and 15], which were repeated as often as possible every four weeks. Pharmacokinetic analysis was done at DOC 40 mg/m2/day. Initially, patients were administered S-1 and 40 mg/m2/day of DOC, and DOC 40 mg/m2/day was considered as MTD. In detail, one patient developed neutropenia (grade 4, G4), and two other patients had no day 15 DOC administration because of neutropenia (grade 3, G3). When S-1 and 35 mg/m2/day of DOC were administered to three patients, no adverse reactions were noted. In six patients treated with S-1 and 30 mg/m2/day of DOC, one patient developed neutropenia (G4), and another patient developed diarrhea (G3) and anorexia (G3). The rest of this cohort showed no adverse reactions. Although 5-fluorouracil and gimeracil concentrations remained high under impaired renal function, no pharmacokinetic interactions appeared between S-1 and DOC under normal renal function. The dose limiting toxicity of a combination of S-1 and biweekly DOC was leukopenia and neutropenia. The recommended dose for this combination in phase II study is DOC 35 mg/m2/day.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. takahashii@matsuyama.jrc.or.jp
authors.forename: Ikuo
authors.initials: I
authors.lastname: Takahashi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Emi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Shin
authors.initials: S
authors.lastname: Ushiro
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004334:Drug Administration Schedule; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000139:chemically induced; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D011725:Pyridines; D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel