title: [Phase I study of S-1. S-1 Study Group].
abstract: We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).
authors.affiliation: Osaka University, Japan Society for Cancer Chemotherapy.
authors.forename: T
authors.initials: T
authors.lastname: Taguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Inuyama
authors.forename: R
authors.initials: R
authors.lastname: Kanamaru
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: S
authors.initials: S
authors.lastname: Akazawa
authors.forename: H
authors.initials: H
authors.lastname: Niitani
authors.forename: H
authors.initials: H
authors.lastname: Furue
authors.forename: M
authors.initials: M
authors.lastname: Kurihara
authors.forename: K
authors.initials: K
authors.lastname: Ota
authors.forename: S
authors.initials: S
authors.lastname: Suga
authors.forename: Y
authors.initials: Y
authors.lastname: Ariyoshi
authors.forename: S
authors.initials: S
authors.lastname: Takai
authors.forename: T
authors.initials: T
authors.lastname: Shimoyama
authors.forename: T
authors.initials: T
authors.lastname: Toge
authors.forename: S
authors.initials: S
authors.lastname: Takashima
authors.forename: K
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Tsukagoshi
authors.forename: I
authors.initials: I
authors.lastname: Nakao
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010094:Oxonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil