Profile and potential of ixabepilone in the treatment of pancreatic cancer

Drug Des Devel Ther. 2014 Jul 14;8:923-30. doi: 10.2147/DDDT.S52964. eCollection 2014.

Abstract

The management of metastatic pancreatic adenocarcinoma is a challenge for medical oncologists because of both the aggressive nature of the disease and the relative paucity of effective systemic treatments with activity against this type of tumor. In the effort to discover new agents and combinations that may augment the therapeutic arsenal available for the management of this cancer, early phase clinical trials have been performed using ixabepilone, an epothilone B analog, with promising results. Targeting the microtubule system with certain taxanes in the management of pancreatic adenocarcinoma has been validated; ixabepilone also targets the microtubule system, interfering with it in an alternate manner from the taxane mechanism. Ixabepilone has demonstrated activity in cancers that have become taxane-resistant as well as those that never had any demonstrable taxane susceptibility. The available data for the use of ixabepilone in the management of pancreatic adenocarcinoma are limited but promising. Single-arm studies have demonstrated both clinical efficacy and tolerable toxicity for the use of ixabepilone as monotherapy. The trial data available for ixabepilone used as a part of combination therapy are similar: it has been paired with chemotherapy (carboplatin, irinotecan) and biologic therapy (dasatinib, sunitinib) at the Phase I level to treat solid tumors in general, again with tolerable side effects and a suggestion of benefit. A single Phase II study has evaluated combination therapy with ixabepilone in the management of patients with pancreatic cancer, pairing it with cetuximab with clinical benefit. Although these trials are promising with regard to addition of ixabepilone to the slim armamentarium for management of pancreatic cancer, further work is still to be done. Importantly, this work bears the burden of not only validating the clinical benefit of ixabepilone, but also of determining whether this benefit is enhanced in any way by combination therapy, and where ixabepilone fits in the sequence of management for patients with metastatic pancreatic cancer.

Keywords: ixabepilone; microtubules; pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Drug Resistance, Neoplasm
  • Epothilones / adverse effects
  • Epothilones / pharmacology
  • Epothilones / therapeutic use*
  • Humans
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Tubulin Modulators / adverse effects
  • Tubulin Modulators / pharmacology
  • Tubulin Modulators / therapeutic use

Substances

  • Epothilones
  • Tubulin Modulators
  • ixabepilone