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, vincristine, doxorubicin, and etoposide (CODE) plus granulocyte colony-stimulating factor (GCSF) compared with cyclophosphamide, doxorubicin, and vincristine, alternating with cisplatin and etoposide (CAV/PE) for extensive-disease (ED) small-cell lung cancer (SCLC), Patients and Methods: Two hundred twenty-seven patients were randomized. CODE consisted of cisplatin 25 mg/m(2) weekly for 9 weeks; vincristine 1 mg/m(2) on weeks 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 administered on the days when chemotherapy was not administered, CAV/PE consisted of cyclophosphamide 800 mg/m(2); doxarubicin 50 mg/m(2) ; and vincristine 1.4 mg/m(2) on day 1, which alternated every 3 weeks with cisplatin 80 mg/m(2) on day 1 and etoposide 100 mg/m(2) on days 1 to 3, Results: Overall response rates were 77% for the CAV/PE arm and 84% for the CODE arm respectively (15% complete response in both arms). The median 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 arms. The incidence of leukopenia did not differ between the two arms, but anemia and thrombocytopenia had a significantly higher incidence in the CODE arm. Four treatment-related deaths from neutropenic fever occurred in the CODE arm, Conclusion: The CODE group had a similar median survival to the CAV/PE group. It does not appear that CODE is a useful approach to improve survival in ED SCLC.