CAN CYTOTOXIC DOSE-INTENSITY BE INCREASED BY USING GRANULOCYTE-COLONY-STIMULATING FACTOR - A RANDOMIZED CONTROLLED TRIAL OF LENOGRASTIM IN SMALL-CELL LUNG-CANCER

Purpose: The use of granulocyte colony-stimulating factor (G-CSF) to increase cytotoxic dose-intensity was assessed in a randomized trial in better-prognosis small-cell lung cancer (SCLC). Both control and G-CSF arms were subject to the same dose-intensification strategy. Patients and Methods: Patients with newly diagnosed SCLC and either no or one adverse prognostic factor were randomized to receive vincristine, ifosfamide, carboplatin, and etoposide (VICE) alone or with recombinant human (rHu)G-CSF (lenograstim) 5 mu g/kg/d between cycles. Six chemotherapy cycles were given, with prophylactic cranial irradiation after cycle 1 and thoracic irradiation after cycle 3. There was no fixed dose interval. In both arms, patients were eligible for re-treatment when the WBC count was greater than or equal to 3 x 10(9)/L and platelet count was greater than or equal to 100 x 10(9)/L. No dose reductions were permitted. Dose-intensity was expressed relative to standard every-4-weeks VICE. Results: Sixty-five consecutive patients in one institution were randomized to control(n = 31) or G-CSF (n = 34). WBC and neutrophil counts were consistently higher in G-CSF patients than in the control group, but there were no significant differences in the incidence of febrile neutropenia, antibiotic or transfusion requirements, or days in hospital. In both treatment arms, the median dose-intensity was greater than one for each cycle (control group, P = .0009; G-CSF group, P = .0001). The G-CSF group received a significantly higher dose-intensity than the control group, with the greatest difference in the first three cycles (1.34 v 1.17, P = .001). There were more chemotherapy-related deaths in the G-CSF group than in the control group (six v one), but this group had a better 2-year survival rate (32% with G-CSF, 95% confidence interval [CI], 16 to 48; 15% with controls, 95% CI, 2 to 27). Conclusion: The dose-intensity of VICE chemotherapy was increased in both groups. patients randomized to receive G-CSF achieved a significantly higher dose-intensity than controls. Despite early toxicity, they had a better 2-year survival rate. (C) 1995 by American Society of Clinical Oncology.