MULTI-DAY FRACTIONATED ADMINISTRATION SCHEDULE FOR PACLITAXEL

Purpose: To establish the feasibility of fractionating paclitaxel admi nistration by utilizing daily one-hour infusions for three, four or fi ve days with dose escalating to determine the patterns of hematologic and non hematologic toxicities. Patients and methods: Forty patients r eceived 87 courses of daily fractionated paclitaxel for three, four or five days; cycles were repeated every 21 days. Six patients received concomitant daily cisplatin. The median number of cycles delivered per patient was two with a range of one to six. Results: Cumulative doses per cycle ranged from 120 mg/m(2) to 250 mg/m(2) with 25% of the cycl es delivering 200 mg/m(2) Or more. Ten cycles (11.5%) were associated with dose limiting neutropenia (grade 3 [7 cycles]; grade 4 [3 cycles] ). No hypersensitivity reactions were observed and no patient required cytokine support. No patient required hospitalization. Conclusion: Ad ministering paclitaxel on a daily fractioned schedule in an ambulatory setting is logistically feasible; does not require premedication; is associated with a toxicity pattern similar to single day schedules (e. g. 24-hour or three-hour infusion); is capable of delivering a higher dose per cycle than published 96- or 120-hour infusion schedules; and could pos sibly be escalated to doses higher than 250 mg/m(2) in caref ully selected patients. The optimal dose rate for five-day multifracti onated administration of paclitaxel is 40 to 50 mg/m(2)/d or a cumulat ive cycle dose of 200 to 250 mg/m(2) and does not require cytokine usa ge. Adding cisplatin on a fractionated daily schedule may accentuate t he neurotoxicity associated with both agents. A prospective comparison of four-day fractionated vs. four-day continuous infusional paclitaxe l has been proposed as a randomized study to determine clinical differ ences in response, dose intensity and toxicity.