title: Maximum-tolerated dose defined for single-agent gemcitabine: a phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  We conducted a phase I trial of the novel nucleoside analog, gemcitabine, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose and efficacy in this population.
  
  
  METHODS
  Eligibility requirements included stage III or IV NSCLC, performance status < or = 1, and no prior chemotherapy. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks every 4 weeks. We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m2/wk (three patients per cohort). Responses were assessed after every two courses (8 weeks).
  
  
  RESULTS
  We treated 33 chemotherapy-naive patients with stage III (n = 5) or IV (n = 28) NSCLC. Most had performance status 1, and 67% had adenocarcinoma. Eight of 32 assessable patients (25%) achieved a partial response. The projected median survival duration (all patients) is 49 weeks. The maximum-tolerated dose was 2,200 mg/m2/wk for 3 weeks every 4 weeks; dose-limiting toxicity was myelosuppression and reversible transaminase elevation. Other side effects were consistently mild. The maximum dose-intensity achieved with the first two cycles was 2,362 mg/m2/wk for 3 weeks every 4 weeks, which is a feasible phase II starting dose.
  
  
  CONCLUSIONS
  This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/wk for 3 consecutive weeks every 4 weeks; this is much higher than that previously reported in heavily pretreated patients. Twenty-five percent of patients with advanced NSCLC achieved a partial response to gemcitabine. This significant activity in conjunction with a very favorable toxicity profile supports the further evaluation of gemcitabine in combination with other active agents.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, USA.
authors.forename: F V
authors.initials: FV
authors.lastname: Fossella
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: P
authors.initials: P
authors.lastname: Tarassoff
authors.forename: M
authors.initials: M
authors.lastname: Calayag-Jung
authors.forename: R
authors.initials: R
authors.lastname: Perez-Soler
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: W K
authors.initials: WK
authors.lastname: Murphy
authors.forename: B
authors.initials: B
authors.lastname: Glisson
authors.forename: E
authors.initials: E
authors.lastname: Rivera
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine