PHASE-I AND PHARMACOLOGICAL STUDY OF PACLITAXEL ADMINISTERED WEEKLY IN PATIENTS WITH RELAPSED OVARIAN-CANCER

Purpose: Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fraction ated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m(2)) administered weekly as a 1-h our infusion in patients with recurrent ovarian cancer. All patients h ad received prior paclitaxel and cisplatin therapy, All patients recei ved standard premedication. Patients and Methods: Eighteen patients ar e assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five), The mean paclitaxel-free interval was 10.1 month s (range, 1 to 24). Results: A total of 194 cycles of therapy were adm inistered with a mean of 10 (range, one to 12) per patient. No mucosit is or grade III neuropathy was seen, Alopecia occurred in one out of 1 8 assessable patients, The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m(2)) delivered, dose-intensity was 90.75% of that planned and greeter than two fold the standard dose-intensity . partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week pacli taxel schedules switched to a weekly schedule with demonstrated respon se. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R(2) = .614). Dose-limiting toxicity was reached at 100 mg/m(2) with two of three patients experiencing a treatment delay, thu s defining a maximum-tolerated dose of 80 mg/m(2) in this group of hea vily pretreated patients on this weekly schedule. Conclusion: (1) Pacl itaxel administered as a 1-hour infusion is well tolerated; (2) this s chedule of administration does not result in cumulative myelosuppressi on; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile. (C) 1997 by Ame rican Society of Clinical Oncology.