PHASE-III STUDY OF INTENSIVE WEEKLY CHEMOTHERAPY WITH RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR VERSUS STANDARD CHEMOTHERAPY IN EXTENSIVE-DISEASE SMALL-CELL LUNG-CANCER

Purpose: To evaluate the therapeutic significance of cisplatin, vincri stine, doxorubicin, and etoposide (CODE) plus granulocyte colony-stimu lating factor (GCSF) compared with cyclophosphamide, doxorubicin, and vincristine, alternating with cisplatin and etoposide (CAV/PE) for ext ensive-disease (ED) small-cell lung cancer (SCLC), Patients and Method s: Two hundred twenty-seven patients were randomized. CODE consisted o f cisplatin 25 mg/m(2) weekly for 9 weeks; vincristine 1 mg/m(2) on we eks 1,2, 4, and 6; and doxorubicin 40 mg/m(2) and etoposide 80 mg/m(2) for 3 days on weeks 1, 3, 5, 7,and 9, G-CSF 50 mu g/m(2) was administ ered on the days when chemotherapy was not administered, CAV/PE consis ted of cyclophosphamide 800 mg/m(2); doxarubicin 50 mg/m(2) ; and vinc ristine 1.4 mg/m(2) on day 1, which alternated every 3 weeks with cisp latin 80 mg/m(2) on day 1 and etoposide 100 mg/m(2) on days 1 to 3, Re sults: Overall response rates were 77% for the CAV/PE arm and 84% for the CODE arm respectively (15% complete response in both arms). The me dian survival times were 10.9 months in the CAV/PE arm and 11.6 months in the CODE arm (P = .1034). The achieved dose-intensity for CODE was approximately twice that for CAV/PE for those drugs common to both ar ms. The incidence of leukopenia did not differ between the two arms, b ut anemia and thrombocytopenia had a significantly higher incidence in the CODE arm. Four treatment-related deaths from neutropenic fever oc curred in the CODE arm, Conclusion: The CODE group had a similar media n survival to the CAV/PE group. It does not appear that CODE is a usef ul approach to improve survival in ED SCLC.