Ixabepilone for the treatment of solid tumors: a review of clinical data

@article{Denduluri2008IxabepiloneFT,
  title={Ixabepilone for the treatment of solid tumors: a review of clinical data},
  author={Neelima Denduluri and Sandra M. Swain},
  journal={Expert Opinion on Investigational Drugs},
  year={2008},
  volume={17},
  pages={423 - 435}
}
Background: Microtubule stabilizing agents such as taxanes are an integral part of therapy for multiple solid tumors. However, due to limitations of these agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an epothilone B analog, is a novel microtubule stabilizing agent. Objective: This review provides an updated summary of emerging clinical experience with Ixabepilone. Methods: Phase I, II and III clinical trials presented in abstract form or journal articles found… 

Ixabepilone: in locally advanced or metastatic breast cancer.

Ixabepilone, an analogue of the natural product epothilone B, stabilizes microtubules resulting in cell cycle arrest and apoptosis, has shown antitumour activity in tumour cell lines in vitro and in several animal tumour models, including those that display key mechanisms of resistance to other anticancer agents.

Structural basis of noscapine activation for tubulin binding.

Structural studies show that the cytotoxic agent 7A-O-demethoxy-amino-noscapine (7A-aminonoscapine) binds to the colchicine site of tubulin, and it is proposed that the anticancer activity of noscapine arises from a bioactive metabolite that binds toThe colchichine siteof tubulin to induce mitotic arrest through a microtubule cytoskeleton-based mechanism.

A structure-activity relationship study on multi-heterocyclic molecules: two linked thiazoles are required for cytotoxic activity.

This is the first detailed comparison of biological activity between multi-heterocyclic containing fragments, and it showed that activity required at least two thiazoles sequentially connected.

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Clinical phase I and early phase II data suggest that epothilones have a broad range of antitumor activity at doses and schedules associated with tolerable side effects and are effective in paclitaxel-resistant tumor models.

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Women with metastatic breast cancer previously untreated with taxanes have a meaningful durable response to single-agent ixabepilone therapy, and minimal hematologic toxicity and no grade 3 sensory neuropathy were noted.

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An objective response was seen in 22% of the patients in a population who had been previously treated with a taxane, and microtubule stabilization occurred in tumor biopsies after treatment with ixabepilone.

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