SEQUENTIAL ADMINISTRATION OF DOXORUBICIN AND PACLITAXEL FOLLOWED BY CYCLOPHOSPHAMIDE, METHOTREXATE AND 5-FLUOROURACIL COMBINATION (CMF) IN WOMEN WITH METASTATIC BREAST-CANCER

Although the combination of paclitaxel with doxorubicin has yielded hi gh response rates in metastatic breast cancer, severe cardiotoxic even ts have been reported in several patients, The rationale for our study was to evaluate the activity of paclitaxel/doxorubicin combination in patients with this disease but to avoid excessive cardiotoxicity, The refore, we administered 4 cycles of doxorubicin/paclitaxel followed by 6 cycles of standard cyclophosphamide, methotrexate and 5-fluorouraci l (CMF) regimen. Study medication consisted of doxorubicin 60 mg/m(2) as a 15-min intravenous infusion followed by paclitaxel 175 mg/m(2) as a 3-hour infusion. CMF regimen consisted of cyclophosphamide 600 mg/m (2) as 1-hour intravenous infusion followed by methotrexate 40 mg/m(2) and 5-fluorouracil 600 mg/m(2) bolus injection. The main toxicity of doxorubicin/paclitaxel treatment phase was neutropenia (WHO grade 3/4, 58%), but we observed only one cardiac adverse event. Toxicities of t he CMF treatment phase were not significant. Of 24 patients evaluable for response, 2 (8%) had complete responses and 11 (46%) achieved part ial response. Ten additional patients (42 %) had stable disease. The m edian time to progression was 12 months and the median overall surviva l was 18.5 months, The sequential administration of doxorubicin and pa clitaxel followed by CMF appeared active and well tolerated in patient s with metastatic breast cancer.