title: Phase I study of the novel taxane CT-2103 in patients with advanced solid tumors.
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.
authors.affiliation: Division of Hematology-Oncology, Abramson Cancer Center, University of Pennsylvania, 51 N 39th Street, MAB-103, Philadelphia, PA 19104, USA. maria.veronese@uphs.upenn.edu
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Veronese
authors.forename: Keith
authors.initials: K
authors.lastname: Flaherty
authors.forename: Amy
authors.initials: A
authors.lastname: Kramer
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Konkle
authors.forename: Mark
authors.initials: M
authors.lastname: Morgan
authors.forename: James P
authors.initials: JP
authors.lastname: Stevenson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Dwyer
mesh_terms: D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000031:analogs & derivatives; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D011099:Polyglutamic Acid / Q000009:adverse effects / Q000627:therapeutic use* / Q000031:analogs & derivatives; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D017211:Treatment Failure
chemical_list: D043823:Taxoids; D011099:Polyglutamic Acid; D017239:Paclitaxel; C509139:paclitaxel poliglumex