title: Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group.
abstract: OBJECTIVE
  To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC).
  
  
  METHODS
  Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm.
  
  
  RESULTS
  The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different.
  
  
  CONCLUSIONS
  The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.
authors.affiliation: National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada. nmurray@bccancer.bc.ca
authors.forename: N
authors.initials: N
authors.lastname: Murray
authors.forename: R B
authors.initials: RB
authors.lastname: Livingston
authors.forename: F A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: K
authors.initials: K
authors.lastname: James
authors.forename: B
authors.initials: B
authors.lastname: Zee
authors.forename: A
authors.initials: A
authors.lastname: Langleben
authors.forename: M
authors.initials: M
authors.lastname: Kraut
authors.forename: J
authors.initials: J
authors.lastname: Bearden
authors.forename: J W
authors.initials: JW
authors.lastname: Goodwin
authors.forename: C
authors.initials: C
authors.lastname: Grafton
authors.forename: A
authors.initials: A
authors.lastname: Turrisi
authors.forename: D
authors.initials: D
authors.lastname: Walde
authors.forename: H
authors.initials: H
authors.lastname: Croft
authors.forename: D
authors.initials: D
authors.lastname: Osoba
authors.forename: J
authors.initials: J
authors.lastname: Ottaway
authors.forename: D
authors.initials: D
authors.lastname: Gandara
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002170:Canada; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D014481:United States; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin