Multi-day fractionated administration schedule for paclitaxel

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Abstract
To establish the feasibility of fractionating paclitaxel administration by utilizing daily one-hour infusions for three, four or five days with dose escalating to determine the patterns of hematologic and non hematologic toxicities. Forty patients received 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. Cumulative doses per cycle ranged from 120 mg/m2 to 250 mg/m2 with 25% of the cycles delivering 200 mg/m2 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 hos-pitalization. Administering 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 possibly be escalated to doses higher than 250 mg/m2 in carefully selected patients. The optimal dose rate for five-day multifrac-tionated administration of paclitaxel is 40 to 50 mg/m2/d or a cumulative cycle dose of 200 to 250 mg/m2 and does not require cytokine usage. Adding cisplatin on a fractionated daily schedule may accentuate the neurotoxicity associated with both agents. A prospective comparison of four-day fractionated vs. four-day continuous infusional paclitaxel has been proposed as a randomized study to determine clinical differences in response, dose intensity and toxicity.