A phase I study of ifosfamide and doxorubicin with recombinant human granulocyte colony-stimulating factor in stage IV breast cancer.

Our objective was to define the maximum tolerated dose of an escalating dose of ifosfamide in combination with a fixed dose of doxorubicin supported by granulocyte colony-stimulating factor (Neupogen). Eighteen women with stage IV breast cancer were enrolled in a Phase I study of an escalating dose of ifosfamide (1.2 g/m2/day for 5 days-2.75 g/m2/day for 5 days) with doxorubicin 20 mg/m2/day for 3 days. Granulocyte colony-stimulating factor was used at 5 microgram/kg on day 6 until hematological recovery. Prophylactic antibiotics were also used. The maximum tolerated dose of ifosfamide in combination with doxorubicin was 2.75 g/m2/day for 5 days. The objective response rate was 83% with a complete response rate of 33% (6/18 patients); the median time to treatment failure was 11.5 months. The median survival has not been reached and will exceed 18 months. We concluded that the recommended dose of ifosfamide in combination with doxorubicin is 2.5 g/m2/day for 5 days. This combination shows promise in stage IV breast cancer.