DOSE-RANGING STUDY OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN SMALL-CELL LUNG-CARCINOMA

Purpose: This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered. Patients and Methods: A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 mu g/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle. Results: In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/mu L, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P less than or equal to .01). In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.% of projected dose) versus 36% of observation patients. During days 5 to 21 of cycle 1, fewer patients who received 10 mu g/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P less than or equal to .01). Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paesthesia, diarrhea, myalgia, musculoskeletal pain, pruritus, and rash (P less than or equal to .10). Fewer occurred more frequently in the 10- and 20-mu g/kg rhGM-CSF groups than in the observation groups. The incidence in the 5-mu g/kg group was comparable to that in observation patients. Patients who received rhGM-CSF had a higher incidence of thrombocytopenia. Conclusion: rhGM-CSF at 5 to 10 mu g/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies.