title: A phase I study of S-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients.
abstract: BACKGROUND
  This phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment.
  
  
  METHODS
  Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m² (level 1), 80 mg/m² (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m², 100 mg/day for BSA 1.25-1.5 m², and 120 mg/day for BSA more than 1.5 m² on days 1-14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade ≥ 3 neutropenia with fever over 38°C, grade ≥ 3 thrombocytopenia, or grade ≥ 3 major nonhematological toxicities.
  
  
  RESULTS
  Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose.
  
  
  CONCLUSIONS
  The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m² combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients.
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoda
authors.forename: Kenzo
authors.initials: K
authors.lastname: Soejima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasuda
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawada
authors.forename: Hideo
authors.initials: H
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakachi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Satomi
authors.forename: Sohei
authors.initials: S
authors.lastname: Nakayama
authors.forename: Sinnosuke
authors.initials: S
authors.lastname: Ikemura
authors.forename: Hideki
authors.initials: H
authors.lastname: Terai
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Maiko
authors.initials: M
authors.lastname: Morosawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Asano
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin