A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: a Southwest Oncology Group study

Invest New Drugs. 2006 Nov;24(6):515-20. doi: 10.1007/s10637-006-8440-x.

Abstract

Purpose: The purpose of this Phase II multi-institutional study was to define the efficacy and toxicity of ixabepilone in patients with advance pancreatic adenocarcinoma.

Patients and methods: Patients were required to have pancreatic adenocarcinoma and metastatic or recurrent disease that was not amenable to curative resection. Performance status was 0-1, and patients could not have had prior chemotherapy, or chemoradiation therapy for their advanced disease although prior local palliative radiation was allowed. Ixabepilone was administered iv as a 3 hour infusion every 21 days. Initially, the dose was 50 mg/m(2) but this was lowered to 40 mg/m(2) shortly after the trial opened because of concerns about neurotoxicity.

Results: Sixty-two patients were registered however 2 were ineligible because they did not have recurrent or metastatic disease. For the 60 eligible patients, 22 had performance status of 0 and 38 performance status of 1. The estimated 6-month survival was 60% (95% CI 48%-72%) with a median survival of 7.2 months and an estimated time to treatment failure of 2.3 months. Out of 56 patients with measurable disease there were 5 confirmed partial responses for a confirmed response probability of 9% (95% CI 3%-20%) and 7 unconfirmed partial responses for an overall response probability of 21% (95% CI 12%-34%). Common toxicities were neutropenia/granulocytopenia, nausea and vomiting and neuropathy. There was one death, cause not determined but judged "possibly" related to treatment.

Conclusion: Ixabepilone shows encouraging activity in patients with advanced pancreatic cancer and should be investigated further in this disease.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Epothilones / adverse effects
  • Epothilones / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome
  • Tubulin Modulators / adverse effects
  • Tubulin Modulators / therapeutic use*

Substances

  • Epothilones
  • Tubulin Modulators
  • ixabepilone