title: Randomized Phase II Study of Adjuvant Chemotherapy with Long-term S-1 versus Cisplatin+S-1 in Completely Resected Stage II-IIIA Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non-small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome.
  
  
  METHODS
  A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m(2)) on day 1 plus oral S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity.
  
  
  RESULTS
  The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3-74.0%) in the S group and 58.1% (95% CI, 47.7-67.2%) in the CS group. The only gene with interaction of P < 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine.
  
  
  CONCLUSIONS
  Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy.
authors.affiliation: Department of Medical Oncology, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Thoracic Surgery, Kinki University Faculty of Medicine, Osakasayama, Japan. mitsudom@surg.med.kindai.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Biostatistics, Yokohama City University, Yokohama, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Department of General Thoracic Surgery, Osaka City General Hospital, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takahama
authors.affiliation: Department of Thoracic Surgery, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shuntougun, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Thoracic Surgery, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Department of Thoracic Oncology, Kinki-chuo Chest Medical Center, Sakai, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Atagi
authors.affiliation: Department of Surgical Oncology, Hiroshima University Graduate School of Medicine, Hiroshima, Japan.
authors.forename: Morihito
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Medical Oncology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saka
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin