title: Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38.
  
  
  METHODS
  Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m(2)) after CPT-11 administration on day 1.
  
  
  RESULTS
  Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32. 7% ) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to < or = 40 mg/m(2) in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies.
  
  
  CONCLUSIONS
  CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.
authors.affiliation: Vanderbilt University, Nashville, TN 37232, USA. russell.devore@mcmail.vanderbilt.edu
authors.forename: R F
authors.initials: RF
authors.lastname: DeVore
authors.forename: D H
authors.initials: DH
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: J
authors.initials: J
authors.lastname: Garst
authors.forename: I W
authors.initials: IW
authors.lastname: Dimery
authors.forename: J
authors.initials: J
authors.lastname: Eckardt
authors.forename: S G
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: G L
authors.initials: GL
authors.lastname: Elfring
authors.forename: L J
authors.initials: LJ
authors.lastname: Schaaf
authors.forename: C K
authors.initials: CK
authors.lastname: Hanover
authors.forename: L L
authors.initials: LL
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin