PHASE-I STUDY WITH A WEEKLY 1 H INFUSION OF PACLITAXEL IN HEAVILY PRETREATED PATIENTS WITH METASTATIC BREAST AND OVARIAN-CANCER

Paclitaxel has proven to be an active agent in the treatment of breast and ovarian cancer [Seidman AD, Ann Oncol 1994, S (Suppl. 6), 17-22], but the optimal dose and schedule remain undefined. We performed a ph ase I study with a weekly Ih infusion of paclitaxel. After premedicati on, patients received a 1 h infusion of paclitaxel on days 1, 8, 15, 2 2, 29 and 36 (every 50 days) using the following dose levels: dose lev el 1 70 mg/m(2), dose level 2 80 mg/m(2), dose level 90 mg/m(2), dose level 4 100 mg/m(2). 20 patients (17 breast, 3 ovarian cancer) with an thracycline- or platinum-refractory disease entered this trial. No dos e limiting toxicities occurred at dose levels 1-3. 2 of the 4 patients at dose level 4 had neutropenia WHO grade 4. At all dose levels respo nses could be observed. Maximal tolerable dose (MTD) was reached using dose level 4. Paclitaxel, given in a weekly 1 h infusion, is safe and shows mild toxicity in heavily pretreated breast and ovarian cancer p atients. We recommend dose level 3 for phase II studies.