Phase I/II clinical trial of epirubicin and paclitaxel followed by granulocyte colony-stimulating factor in a 2-week schedule in patients with advanced or metastatic breast cancer

Abstract

Anthracyclines and taxanes are the most potent cytotoxic agents available for treating breast cancer. With combined therapy (either epirubicin or doxorubicin with paclitaxel [Taxol; Bristol-Myers Squibb Company, Princeton, NJ]), response rates of 70% to 90% have been reported. To achieve a maximal dose intensity per week, we decided to combine epirubicin 100 mg/m2 with escalating doses of paclitaxel, at successive dose levels of 135, 150, 165, and 180 mg/m2 in a 2-week schedule, with administration of subcutaneous granulocyte colony-stimulating factor 5 microg/kg from days 2 through 10. To date, 16 patients have been included, with six patients treated at level 1 (100/135 mg/m2 epirubicin/paclitaxel), four at level 2 (100/150 mg/m2), four at level 3 (100/165 mg/m2), and two at level 4 (100/180 mg/m2). The median age of all subjects is 55 years (range, 41 to 65 years). Five patients had received chemotherapy in the adjuvant setting. Of 79 treatment courses, 78 are evaluable for toxicity. The mean number of courses per patient is six (range, two to six courses). At dose level 1, one episode of febrile neutropenia with grade 4 thrombocytopenia occurred. No grade 4 extrahematologic adverse event has been noted so far. At dose level 2, we achieved a dose intensity per week of epirubicin 50 mg/m2 and paclitaxel 75 mg/m2, as expected. At dose level 3, the dose intensity per week was 47.5 mg/m2 and 78.8 mg/m2, respectively (expected 50 and 82.5 mg/m2). The current response rate, evaluated in 14 of 16 patients, is four complete remissions and eight partial remissions, for an overall response rate of 85%. Two patients had stable disease. Granulocyte colony-stimulating factor following epirubicin/paclitaxel on a 2-week schedule permits a very high dose intensity per week for both drugs and produces a high response rate in patients with advanced or metastatic breast cancer.