923 Phase I study of taxol administered weekly in patients with persistent ovarian cancer

Abstract

We commenced a Phase I study of Taxol administered weekly in pts with persistent ovarian cancer to assess feasibility, toxicity and schedule dependency. Cumulative hematologic toxicity has been uncommon with this schedule. In vitro studies with Taxol have suggested that fractionated brief infusion schedules would be more effective than standard 24 H infusion every 21 days. All pts had received prior platinum-based chemotherapy in addition to at least one regimen with Taxol. Pts with a history of grade 3–4 neuropathy were ineligible. Methods Taxol dose levels of 40, 50, 60, 80 and 100 mg/m2 per week were studied. Treatment was administered in the ambulatory clinic with standard Taxol pre-medication. Results 18 pts enrolled, 17 evaluable for toxicity. Overall response in 3/14 (21.4%) pts evaluable, 2 pts with stable disease. Total of 170 Taxol cycles delivered, median 8 per pt (1–18). 166/170 cycles delivered on schedule. Mean WBC nadir following Taxol cycles was 3.8 (0.8–10.4) × 109/L. No cumulative hematologic toxicity has been noted. No alopecia noted. 11 pts entered study with neuropathy, 7 with grade I, 4 with grade II. No grade III neuropathy noted. In spite of Taxol 100 mg/m2/weekly, we have thus far failed to demonstrate dose-limiting toxicity. Dose escalation continues. Conclusions 1) Weekly administration of Taxol on this dose and schedule is feasible. 2) This schedule does not result in cumulative myelosuppression. We commenced a Phase I study of Taxol administered weekly in pts with persistent ovarian cancer to assess feasibility, toxicity and schedule dependency. Cumulative hematologic toxicity has been uncommon with this schedule. In vitro studies with Taxol have suggested that fractionated brief infusion schedules would be more effective than standard 24 H infusion every 21 days. All pts had received prior platinum-based chemotherapy in addition to at least one regimen with Taxol. Pts with a history of grade 3–4 neuropathy were ineligible. Taxol dose levels of 40, 50, 60, 80 and 100 mg/m2 per week were studied. Treatment was administered in the ambulatory clinic with standard Taxol pre-medication. 18 pts enrolled, 17 evaluable for toxicity. Overall response in 3/14 (21.4%) pts evaluable, 2 pts with stable disease. Total of 170 Taxol cycles delivered, median 8 per pt (1–18). 166/170 cycles delivered on schedule. Mean WBC nadir following Taxol cycles was 3.8 (0.8–10.4) × 109/L. No cumulative hematologic toxicity has been noted. No alopecia noted. 11 pts entered study with neuropathy, 7 with grade I, 4 with grade II. No grade III neuropathy noted. In spite of Taxol 100 mg/m2/weekly, we have thus far failed to demonstrate dose-limiting toxicity. Dose escalation continues. 1) Weekly administration of Taxol on this dose and schedule is feasible. 2) This schedule does not result in cumulative myelosuppression.