PHASE-I AND PHARMACOLOGICAL STUDY OF WEEKLY DOXORUBICIN AND 1 HR INFUSIONAL PACLITAXEL IN PATIENTS WITH ADVANCED BREAST-CANCER

Doxorubicin and paclitaxel both display strong antitumor activity in t he treatment of breast cancer. The optimal schedule of this combinatio n, however, remains undefined. In this phase I and pharmacologic study , we administered weekly 12 mg/m(2) doxorubicin as a bolus infusion im mediately followed by a 1 h 80 mg/m(2) paclitaxel infusion to patients with metastatic breast cancer, A total of 119 weekly courses were del ivered to seven patients. Grade IV neutropenia was observed in two pat ients at the first dose level, thus already defining the maximum toler ated dose. Pronounced non-hematologic toxicities were mild neuropathy (grade I: 39%) and stomatitis (grade I: 19%, grade II: 8%), No signs o f cardiac toxicity were observed with this dose schedule, Three partia l responses were achieved in this group of heavily pretreated patients . The pharmacokinetics of paclitaxel, doxorubicin and Cremophor EL wit h this schedule were analyzed. Overall, the schedule was well tolerate d and combined with its preliminary response rate justifies further ev aluation in phase II studies. [[(C) 1998 Lippincott Williams & Wilkins .].