EFFICACY OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR FOR CHEMOTHERAPY-INDUCED LEUKOPENIA IN PATIENTS WITH NON-SMALL-CELL LUNG-CANCER

To assess the feasibility and efficacy of rhGM-CSF in ameliorating che motherapy-induced leukopenia in patients with advanced non-small-cell lung cancer, we conducted a double-blind placebo controlled phase m st udy in a multicenter setting. Patients were eligible if they had cytol ogically or histologically proven cancer, no prior chemotherapy, stage IIIB or IV disease, an Eastern Cooperativve Oncology Group (ECOG) per formance status of 0-2, an age of less than 76 years, and no symptomat ic brain metastasis, disseminated bone metastasis, or previous vertebr al/pelvic irradiation. The chemotherapy regimen consisted of mitomycin given at 8 mg/m(2) on day 1, cisplatin given at 100 mg/m(2) on day 1, and vindesine given at 3 mg/m(2) i.v. on days 1 and 8 (MVP). If the g ranulocyte nadir count recorded after the first cycle of MVP was less than 1,000/mm(3), patients were randomly assigned to receive recombina nt human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) o r placebo during the second cycle of MVP. The dose of rhGM-CSF was 125 mu g/m(2) given daily s.c. for 14 consecutive days starting on day 2. Of the 52 patients enrolled, 45 were evaluable. The nadir of granuloc ytes was significantly lower in the placebo group (P = 0.007). The per iod during which the granulocyte count was less than 1,000/mm(3) was s ignificantly longer in the placebo group (median, 6 vs 10 days; P = 0. 04). The incidence of adverse effects related to rhGM-CSF, such as fev er (greater than or equal to 38 degrees C) and skin rash, was signific antly higher in the rhGM-CSF group (P = 0.011). The rate of response t o chemotherapy did not significantly differ between the two groups. In conclusion, rhGM-CSF reduced the duration of chemotherapy-induced gra nulocytopenia. The clinical usefulness of this agent may be deminished because of the adverse effects encountered when it is used in combina tion with a moderately myelotoxic chemotherapy regimen.