title: A phase I dose escalation study of biweekly gemcitabine and carboplatin in completely resected stage IB-IIIA nonsmall cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I dose escalation study to determine the maximum tolerated dose, recommended dose, and safety profile of a biweekly gemcitabine and carboplatin combination regimen in the treatment of patients with completely resected nonsmall cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with completely resected pathologically documented stage IB, II, or IIIA NSCLC, performance status (ECOG) 0-1, with adequate bone marrow, renal, liver, and cardiac functions, were treated with gemcitabine and carboplatin. The starting dose was gemcitabine 800 mg/m2 on days 1 and 15 and carboplatin area under the time-concentration curve (AUC) 4 mg/mL/min on day 1. Gemcitabine was increased to 1000 mg/m2 (level 3). Carboplatin was increased to AUC 5 (level 2, 3). The regimen was performed every 4 weeks. The dose-limiting toxicity of the regimen was assessed during the first chemotherapy cycle.
  
  
  RESULTS
  Nine patients were enrolled in this study. All patients were assessed for safety. Grade 3 leukopenia occurred in 1 patient (11%) and grade 3/4 neutropenia occurred in 3 patients (33%). No other grade 3/4 toxicity was observed. No dose-limiting toxicity was experienced at dose levels 1, 2, and 3 of this schedule.
  
  
  CONCLUSIONS
  Maximum tolerated dose was not reached in this study. Considering treatment continuation, the recommended dose for a phase II study is gemcitabine 1000 mg/m2 on days 1 and 15 and carboplatin AUC 5 on day 1, every 4 weeks. Biweekly administration of gemcitabine and carboplatin is a feasible and well-tolerated regimen for the treatment of patients with completely resected NSCLC as adjuvant chemotherapy.
authors.affiliation: Department of Respiratory Medicine, National Nishigunma Hospital, Shibukawa, Gunma, Japan. ytomizawa@netnngh.hosp.go.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tomizawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ishihara
authors.forename: Hironobu
authors.initials: H
authors.lastname: Iijima
authors.forename: Hisao
authors.initials: H
authors.lastname: Imai
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Yatomi
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamada
authors.forename: Go
authors.initials: G
authors.lastname: Kobayashi
authors.forename: Emi
authors.initials: E
authors.lastname: Ishida
authors.forename: Teruki
authors.initials: T
authors.lastname: Inoue
authors.forename: Haruka
authors.initials: H
authors.lastname: Aoki
authors.forename: Satoru
authors.initials: S
authors.lastname: Watanabe
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawashima
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Ryusei
authors.initials: R
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006402:Hematologic Diseases / Q000453:epidemiology; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008017:Life Expectancy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine