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 phase I study with a weekly Ih infusion of paclitaxel. After premedication, patients received a 1 h infusion of paclitaxel on days 1, 8, 15, 22, 29 and 36 (every 50 days) using the following dose levels: dose level 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 anthracycline- or platinum-refractory disease entered this trial. No dose 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 responses 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 patients. We recommend dose level 3 for phase II studies.