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 escalatin g dose of ifosfamide in combination with a fixed dose of doxorubicin s upported 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/m(2)/day for 5 days-2.75 g/m( 2)/day for 5 days) with doxorubicin 20 mg/m(2)/day for 3 days. Granulo cyte colony-stimulating factor was used at 5 mu g/kg on day 6 until he matological recovery. Prophylactic antibiotics were also used. The max imum tolerated dose of ifosfamide in combination with doxorubicin was 2.75 g/m(2)/day for 5 days. The objective response rate was 83% with a complete response rate of 33% (6/18 patients); the median time to tre atment failure was 11.5 months. The median survival has not been reach ed and will exceed 18 months. We concluded that the recommended dose o f ifosfamide in combination with doxorubicin is 2.5 g/m(2)/day for 5 d ays. This combination shows promise in stage IV breast cancer.