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Drug Profile

Vintafolide (EC145) for the treatment of folate-receptor-a positive platinum-resistant ovarian cancer Expert Rev. Clin. Pharmacol. 7(4), 443–450 (2014)

Allison J Ambrosio, Daphne Suzin, Edwin L Palmer and Richard T Penson* Division of Hematology Oncology, Yawkey 9-064, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114, USA *Author for correspondence: Tel.: +1 617 726 8566 Fax: +1 617 724 6898 [email protected]

Seminal advances in the treatment of cancer have been achieved because of drug development in ovarian cancer; notably the developments of platinums and taxanes. However, no new drug has been FDA approved for ovarian cancer since 2006, and the approval of an antiangiogenic agent for ovarian cancer in the US has stalled. Predicting the next breakthrough is a high risk and highly expensive venture. One of the most promising prospects is folate-receptor (FR)-targeted therapy, given the high expression in FR ovarian cancer. We review the development of vintafolide (EC145), a folic acid-desacetylvinblastine conjugate, the predictive utility of a FR-targeted imaging agent, technetium-99m-etarfolatide (EC20), the challenges in proving survival advantage, and other approaches to exploiting FR as a target in ovarian cancer. KEYWORDS: chemotherapy • EC145 • EC20 • etarfolatide • novel

Ovarian cancer & platinum resistance

Ovarian cancer has the highest mortality rate of all malignancies of the female reproductive system and ranks in the top 10 female cancers both for new diagnosis and deaths, accounting for a projected 21,980 new diagnoses and 14,270 deaths annually in the USA in 2014 [1]. Screening has not been demonstrated to impact mortality, and symptoms are often non-specific and inconsistent, and so the majority of patients, 61%, are diagnosed at FIGO stage III or IV with widely metastasized disease in the abdomen, which correlates with a poor 5-year survival rate, varying with stage and histology, and 5-year survival for advanced stage patients is 27% [2]. The accepted primary treatment is aggressive cytoreductive surgery followed by a combination course of platinum-based chemotherapy in combination with a taxane; for most patients, carboplatin is preferred over cisplatin due to its better side-effect profile, though for optimally cytroreduced patients (

Vintafolide (EC145) for the treatment of folate-receptor-α positive platinum-resistant ovarian cancer.

Seminal advances in the treatment of cancer have been achieved because of drug development in ovarian cancer; notably the developments of platinums an...
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