title: A phase I study of S-1 combined with weekly cisplatin for metastatic gastric cancer in an outpatient setting.
abstract: A dose-escalation study was conducted for patients with metastatic gastric cancer to determine the recommended dose of weekly intravenous (i.v.) cisplatin combined with a fixed dose of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, on an outpatient basis. Secondary endpoints were to define the toxicity profile and to determine tumour responses. S-1 was fixed at a dose of 70 mg/m(2)/day and was administered for 2 weeks followed by a 1-week rest. Three dose levels of cisplatin (10, 15 and 20 mg/m(2)) were studied. Cisplatin was infused over 30 min on days 1 and 8. 20 patients were enrolled. No dose-limiting toxicities (DLTs) were recorded during the administration of cisplatin up to 20 mg/m(2), except for grade 3 diarrhoea and stomatitis in one patient at dose level 3. No grade 4 adverse events occurred. However, grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in 7 of 13 patients at dose level 3 within the first two treatment cycles. This was determined to be the maximum acceptable level that would not negate the advantages observed with use of an oral drug such as S-1. An objective tumour response was seen at all dose levels, and the overall response rate in the 18 patients evaluated was 61%. A higher response rate of 78% was observed in 9 patients who had received no prior chemotherapy. Oral S-1 with weekly cisplatin is a feasible and promising combination regimen that is appropriate for an outpatient setting. A randomised phase II study comparing this combination with S-1 alone in chemo-nai;ve patients is warranted.
authors.affiliation: Department of Internal Medicine, National Shikoku Cancer Center, 13 Horinouchi, 790-0007, Matsuyama, Japan. ihyodo@shikoku-cc.go.jp
authors.forename: I
authors.initials: I
authors.lastname: Hyodo
authors.forename: T
authors.initials: T
authors.lastname: Nishina
authors.forename: T
authors.initials: T
authors.lastname: Moriwaki
authors.forename: S
authors.initials: S
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Terao
authors.forename: K
authors.initials: K
authors.lastname: Hirao
authors.forename: J
authors.initials: J
authors.lastname: Nasu
authors.forename: S
authors.initials: S
authors.lastname: Hirasaki
authors.forename: H
authors.initials: H
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Masumoto
authors.forename: H
authors.initials: H
authors.lastname: Tajiri
authors.forename: A
authors.initials: A
authors.lastname: Kurita
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin