Schedule-dependent paclitaxel tolerance/activity: data from a 7 day infusion phase I study with pharmacokinetics in paclitaxel refractory ovarian cancer

Anticancer Drugs. 1997 Sep;8(8):763-6. doi: 10.1097/00001813-199709000-00005.

Abstract

Our objective was to determine the maximum tolerated dose (MTD) of paclitaxel when given as a 7 day continuous i.v. infusion, repeated every 3 weeks, and to evaluate the toxicity and the efficacy of such a schedule of administration as a salvage treatment in ovarian cancer patients pretreated and refractory to 3 or 24 h paclitaxel. Thirteen women were enrolled in this phase I trial. Four dose levels ranging from 105 to 157.5 mg/m2/cycle were explored. Two of four patients experienced dose-limiting febrile neutropenia at the dose of 157.5 mg/m2. No objective response was observed, although three patients experienced disease stabilization (five to six cycles), with regression of disease symptoms, two of them having sustained 50% or greater decrease in CA 125. We conclude that the MTD in this population was paclitaxel 140 mg/m2/7 days. Schedule-dependent mechanisms of resistance to paclitaxel could not be demonstrated in this clinical setting of heavily pretreated ovarian cancer patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Tolerance
  • Female
  • Humans
  • Neutropenia / chemically induced
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics*
  • Salvage Therapy
  • Thrombocytopenia / chemically induced

Substances

  • Antineoplastic Agents, Phytogenic
  • Paclitaxel