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JOURNAL ARTICLE
REVIEW
EC-145, a folate-targeted Vinca alkaloid conjugate for the potential treatment of folate receptor-expressing cancers.
Current Opinion in Investigational Drugs 2010 December
EC-145, under development by Endocyte, is a conjugate composed of desacetylvinblastine monohydrazide linked through a peptide spacer to the targeting moiety folic acid, for the potential intravenous treatment of folate receptor-overexpressing tumors, in particular ovarian and lung cancers. In vitro studies demonstrated that EC-145 selectively binds to cells that overexpress the folate receptor, causing dose-dependent cytotoxicity. Furthermore, coincubation of the KB human nasopharyngeal carcinoma cell line with EC-145 and doxorubicin resulted in synergistic antitumor activity. Experiments in mouse tumor xenograft models have confirmed the potency of EC-145 and the curative effects of the drug conjugate were demonstrated in an aggressive lymphoma xenograft model. In a phase I clinical trial in patients with advanced or metastatic solid tumors, adverse events were generally of moderate severity with the most frequent being fatigue, constipation and peripheral sensory neuropathy. Preliminary data from a phase II clinical trial in patients with advanced ovarian cancer demonstrated that third- or fourth-line treatment with EC-145 yielded better disease control than second- or third-line liposomal doxorubicin. Coadministration of EC-145 and liposomal doxorubicin produced a statistically significant increase in progression-free survival over standard therapy in patients with platinum-resistant ovarian cancer. Phase III clinical trials are expected to confirm these promising results.
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