title: [Combination chemotherapy of TS-1 +cisplatin for inoperable gastric cancer].
abstract: There is no chemotherapy considered to be standard treatment for advanced gastric cancer worldwide, and there is no consensus as to whether combination or single agent therapy is preferred. In the phase I portion, a dose-escalation study of cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40 mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2, because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients including 6 patients of the RD phase I portion were evaluated. The median administered courses was 4 (range: 1-8). The incidence of haematological and non-haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9 (90.6%), and the median survival days were 383. This regimen is considered to be active against AGC with acceptable toxicity. In addition, currently, a randomized phase III study (JCOG 9912) for AGC patients not treated previously with chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone and CPT-11 with CDDP therapy. We also initiated a randomized phase III study comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we may be able to evaluate the clinical benefit of TS-1 in combination with CDDP versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival benefits and improving the QOL for AGC patients.
authors.affiliation: Department of Internal Medicine I , Kitasato University, 2-1-1 Asamizodai, Sagamihara 228-8520, Japan.
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanabe
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Higuchi
authors.forename: Toru
authors.initials: T
authors.lastname: Sasaki
authors.forename: Norisuke
authors.initials: N
authors.lastname: Nakayama
authors.forename: Shizuka
authors.initials: S
authors.lastname: Nagaba
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimoda
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.forename: Kento
authors.initials: K
authors.lastname: Nakatani
authors.forename: Katsunori
authors.initials: K
authors.lastname: Saigenji
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D020714:Maximum Tolerated Dose; D010094:Oxonic Acid / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin