title: Phase I trial of the combination of irinotecan, paclitaxel, and carboplatin in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose, toxicities, and dose suitable for phase II/III trials of irinotecan (CPT-11) combined with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with stage IIIB/IV NSCLC were enrolled to this multicenter, phase I study. The initial regimen was paclitaxel 225 mg/m(2)/3 h, followed by carboplatin area under the curve (AUC) 6 over 30 minutes on day 1, and CPT-11 starting at 40 mg/m(2) over 90 minutes, days 1 and 8, every 3 weeks. Dose-limiting toxicity occurred in three of seven patients. The regimen was amended, with doses reduced to paclitaxel 175 mg/m(2)/3 h, carboplatin AUC 5 and CPT-11 at 40 mg/m(2), all on day 1 every 3 weeks. Dose escalation of CPT-11 proceeded to 80 mg/m(2) then 125 mg/m(2) before dose-limiting toxicities were experienced. Subsequent patients received an intermediate CPT-11 dose of 100 mg/m(2).
  
  
  RESULTS
  Thirty-three patients were enrolled; 32 patients were assessable for safety, and 31 were assessable for tumor response. The primary first-cycle dose-limiting toxicities were neutropenia and diarrhea. The most common grade 3/4 toxicity observed during all cycles was neutropenia (16 patients [50%], with six [19%] developing neutropenic fever). Objective tumor response was observed in 39% (12/31, 95% confidence interval, 22% to 58%). The median time to tumor progression was 6.8 months, median survival 11.0 months, and 1-year survival probability 0.46.
  
  
  CONCLUSIONS
  CPT-11 100 mg/m(2), paclitaxel 175 mg/m(2), and carboplatin AUC 5 given every 3 weeks can be safely administered in patients with advanced NSCLC. Neutropenia and diarrhea are the dose-limiting toxicities. The combination shows appreciable activity, and survival data are favorable.
authors.affiliation: Multidisciplinary Thoracic Oncology Program, University of North Carolina, Chapel Hill, NC 27599, USA. socinski@med.unc.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Socinski
authors.forename: A B
authors.initials: AB
authors.lastname: Sandler
authors.forename: L L
authors.initials: LL
authors.lastname: Miller
authors.forename: P K
authors.initials: PK
authors.lastname: Locker
authors.forename: C K
authors.initials: CK
authors.lastname: Hanover
authors.forename: G L
authors.initials: GL
authors.lastname: Elfring
authors.forename: V K
authors.initials: VK
authors.lastname: Israel
authors.forename: N
authors.initials: N
authors.lastname: Pirotta
authors.forename: R B
authors.initials: RB
authors.lastname: Natale
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage*
chemical_list: D000077146:Irinotecan; D016190:Carboplatin; D017239:Paclitaxel; D002166:Camptothecin