Phase I study of the novel taxane CT-2103 in patients with advanced solid tumors

Cancer Chemother Pharmacol. 2005 May;55(5):497-501. doi: 10.1007/s00280-004-0938-3. Epub 2005 Feb 12.

Abstract

Background: CT-2103 (Cell Therapeutics, Seattle, Wash.) is a water-soluble macromolecular conjugate of paclitaxel to a polyglutamate backbone, designed to enhance tumor permeability and to improve intratumoral delivery of paclitaxel. Preclinical studies indicate that CT-2103 has substantial antitumor efficacy in xenograft tumor models.

Methods: We performed a phase I trial in patients with advanced solid tumors to determine the maximum tolerated doses (MTD) of CT-2103 when administered as short intravenous infusion every 3 weeks.

Results: Seven patients received a total of 16 cycles (range 1-3) of CT-2103 at doses of 235 and 270 mg/m(2). Two of five patients treated at 235 mg/m(2) and one of two patients treated at 270 mg/m(2) experienced grade 3/4 neutropenia. Four patients experienced a marked increase in PTT within 30 min of the start of infusion. Neuropathy was more severe than expected. Two patients developed grade 3 neuropathy that prompted a 50% dose reduction of CT-2103 and persisted for 8 months in one, and over a year in the other. Three patients experienced grade 1 or 2 neuropathy. Neurotoxicity was cumulative and prevented patients from receiving prolonged administration of CT-2103.

Conclusions: The unexpectedly high rate of cumulative toxicity observed in our study needs to be taken into consideration in future trials of CT-2103. Prior taxane use may not be a predictor of severe neurotoxicity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Paclitaxel / analogs & derivatives
  • Peripheral Nervous System Diseases / chemically induced*
  • Polyglutamic Acid / adverse effects
  • Polyglutamic Acid / therapeutic use*
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Thrombocytopenia / chemically induced
  • Treatment Failure

Substances

  • Taxoids
  • Polyglutamic Acid
  • Paclitaxel
  • paclitaxel poliglumex