Substantial intensification of chemotherapy doses is a promising approach to the treatment of refractory malignancy currently receiving increasing attention. For the past 4 years we have used 3 repeated cycles of a combination of cyclophosphamide (5 g/m2), etoposide (1500 mg/m2), and cisplatin (150 mg/m2) without replacement of progenitor cells and with and without colony-stimulating factor support. The duration of threatening levels of granulocytopenia with this regimen averages 10.2 days, although an occasional patient has prolonged recovery (range, 5-20 days) and most patients require antibiotic therapy for cytopenic fever. We have not yet identified the optimal dose of GM-CSF, but 500 micrograms/m2 significantly shortens the duration of cytopenia (ANC less than 300/mm3) to 5.9 days with a resultant decrease in incidence and duration of cytopenic fever (from 10.8 to 1.7 days), use of antibiotics (from 10.8 to 7.6 days), and duration of hospitalization (from 22.2 to 16.3 days). Seventeen patients with metastatic breast cancer have received this regimen to date with a 35% complete response (CR) rate and a 53% partial response (PR) rate. Most of these patients were refractory to standard therapy. Four of six (67%) not refractory to standard therapy have achieved complete responses that are ongoing at 3.5 to 10.4 months. We conclude that dose-intensive therapy is an option that needs more careful exploration early in the treatment of advanced breast cancer and that GM-CSF decreases morbidity and risk of dose-intensive regimens.