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.