title: Multi-day fractionated administration schedule for paclitaxel.
abstract: OBJECTIVE
  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. PATTERNS AND METHODS: 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.
  
  
  RESULTS
  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 hospitalization.
  
  
  CONCLUSIONS
  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 multifractionated 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.
authors.affiliation: Cancer Center of Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lokich
authors.forename: N
authors.initials: N
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Bern
authors.forename: F
authors.initials: F
authors.lastname: Coco
authors.forename: E
authors.initials: E
authors.lastname: Dow
authors.forename: C
authors.initials: C
authors.lastname: Moore
authors.forename: T
authors.initials: T
authors.lastname: Zipoli
authors.forename: L
authors.initials: L
authors.lastname: Gonzalves
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel