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

Nevin Murray, Robert B. Livingston, Frances A. Shepherd, Keith James, Benny Zee, A. Langleben, Michael Kraut, James Bearden, J. Wendall Goodwin, Clive Grafton, Andrew Turrisi, David Walde, Herbert Croft, David Osoba, Jon Ottaway, David Gandara

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110 Scopus citations

Abstract

Purpose: 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). Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2300-2308
Number of pages9
JournalJournal of Clinical Oncology
Volume17
Issue number8
StatePublished - Aug 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Murray, N., Livingston, R. B., Shepherd, F. A., James, K., Zee, B., Langleben, A., Kraut, M., Bearden, J., Wendall Goodwin, J., Grafton, C., Turrisi, A., Walde, D., Croft, H., Osoba, D., Ottaway, J., & Gandara, D. (1999). 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. Journal of Clinical Oncology, 17(8), 2300-2308.