Phase 1 trial of ifosfamide and adriamycin in metastatic breast cancer.

OBJECTIVE A Phase 1 trial was conducted in patients with estrogen negative receptors (ER) or hormone refractory metastatic breast cancer to determine the maximum tolerated dose (MTD) of ifosfamide with a fixed dose of doxorubicin. A secondary objective was to determine the efficacy of the combination in metastatic breast cancer. METHODS Fifteen patients were entered in the study in cohorts of three patients at each dose level of ifosfamide. The dose of doxorubicin was fixed at 45 mg/m2. Five different dose levels of ifosfamide were tested ranging from dose level 1 of 1.5 gms/m2 day 1-3 to level V at 2.5 gms/m2 day 1-3. RESULTS Dose escalation of ifosfamide was stopped at 2.5 gms/m2. The MTD of ifosfamide was 2.25 gms/m2 day 1-3 in combination with doxorubicin. All patients in the study were assessable for toxicity. Neutropenia and thrombocytopenia were the major dose limiting toxicities. Other toxicities included anemia, confusion and hematuria. Objective responses were documented in 11 of 15 patients (73.3%). Median time to treatment failure (TTF) was 13 months. Median overall survival (OS) was 18 months. CONCLUSION The combination of ifosfamide and doxorubicin was a practical well tolerated regimen. There was substantial evidence of clinical activity in this phase I trial. This combination should be further evaluated, as an attractive alternative to taxanes for patients in developing countries where cost effectiveness is important.