title: Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer.
abstract: OBJECTIVE
  Etoposide and cisplatin (EP) has been a standard treatment for extensive-disease small-cell lung cancer (SCLC). An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin (IP) versus EP. Our trial was designed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP.
  
  
  METHODS
  The primary objective was to compare overall survival in extensive-disease SCLC patients randomly assigned to receive IP (n = 221) or EP (n = 110). Patients were randomly assigned in 2:1 ratio to cisplatin 30 mg/m2 intravenously (IV) + irinotecan 65 mg/m2 IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m2 IV on day 1, and etoposide 120 mg/m2 IV on days 1 to 3 every 21 days for at least four cycles, until progressive disease, or until intolerable toxicity resulted.
  
  
  RESULTS
  Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v 86.5%; P < .01), febrile neutropenia (3.7% v 10.4%; P = .06), anemia (4.8% v 11.5%; P = .02), thrombocytopenia (4.3% v 19.2%; P < .01), vomiting (12.5% v 3.8%; P = .04), and diarrhea (21.3% v 0%; P < .01). There was no significant difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6 months), or overall survival (median survival time, 9.3 months v 10.2 months; P = .74).
  
  
  CONCLUSIONS
  Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.
authors.affiliation: Indiana University, Indianapolis, IN 46202, USA. nhanna@iupui.edu
authors.forename: Nasser
authors.initials: N
authors.lastname: Hanna
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.forename: Corey
authors.initials: C
authors.lastname: Langer
authors.forename: Lawrence
authors.initials: L
authors.lastname: Einhorn
authors.forename: Troy
authors.initials: T
authors.lastname: Guthrie
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Beck
authors.forename: Rafat
authors.initials: R
authors.lastname: Ansari
authors.forename: Peter
authors.initials: P
authors.lastname: Ellis
authors.forename: Michael
authors.initials: M
authors.lastname: Byrne
authors.forename: Mark
authors.initials: M
authors.lastname: Morrison
authors.forename: Subramanian
authors.initials: S
authors.lastname: Hariharan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wang
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin