title: Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a west Japan oncology group study.
abstract: OBJECTIVE
  The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days.
  
  
  RESULTS
  At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm.
  
  
  CONCLUSIONS
  Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.
authors.affiliation: Kinki University Faculty of Medicine, Osaka City General Hospital, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan. chi-okamoto@dotd.med.kindai.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ando
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Saka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Asami
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirashima
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kurata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D016190:Carboplatin; D017239:Paclitaxel