Phase 2 trial of epothilone B analog BMS-247550 (ixabepilone) in advanced carcinoma of the urothelium (E3800): a trial of the Eastern Cooperative Oncology Group

Cancer. 2007 Aug 15;110(4):759-63. doi: 10.1002/cncr.22839.

Abstract

Background: Paclitaxel and docetaxel are active agents in advanced urothelial cancer. BMS-247550 (ixabepilone) has activity in preclinical models in paclitaxel resistant models. A phase 2 trial of this epothilone was performed to determine the activity and toxicity of this agent in a multi-institutional setting in patients previously treated with 1 prior chemotherapy regimen.

Methods: Forty-five patients with advanced urothelial carcinoma were treated with BMS-247550 40 mg/m(2) over 3 hours intravenously on Day 1 of a 21-day cycle and continued therapy until progression or unacceptable toxicity.

Results: Five patients obtained an objective partial response (PR) among the 42 eligible patients for an overall response rate of 11.9% (90% confidence interval [5.3%, 26.5%]). Median overall survival of the group was 8 months. Toxicity was moderate with granulocytopenia, fatigue, and sensory neuropathy being the most common side effects noted.

Conclusions: BMS-247550 (ixabepilone) has very modest activity as a second-line therapy for advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and sensory neuropathy was common.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Agranulocytosis / chemically induced
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / pathology
  • Epothilones / adverse effects
  • Epothilones / therapeutic use*
  • Female
  • Fever / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Prognosis
  • Survival Analysis
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Epothilones
  • ixabepilone