Profile of vintafolide (EC145) and its use in the treatment of platinum-resistant ovarian cancer Mathieu Luyckx,1,2 Raffaella Votino,1 Jean-Luc Squifflet,1,2 Jean-François Baurain2,31Gynecology and Andrology Unit, 2Centre du cancer, Gynecologic Oncology Group, 3Medical Oncology Unit, Cliniques Universitaires Saint-Luc, Brussels, BelgiumObjective: Our aim was to review the profile of vintafolide (EC145) and its rationale for use in platinum-resistant ovarian cancer. First we investigated the folate receptors (FRs), folate's pathway into cells, and its expression in normal and cancerous cells, before detailing the mechanism of action of vintafolide, its clinical applications, and the results of different study phases.Materials and methods: A literature search was conducted through Pubmed/Medline, Google, ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in English were selected. All articles investigating folate receptor expression in ovarian cancer were selected first, than articles reviewing platinum resistance. Papers about vintafolide were collected, while those talking about synthesis and biochemistry concerns were excluded. The different Phase I and II studies were read, and an update on the website of pharmaceuticals companies were added.Results: FR is a bundle-membrane receptor that is expressed normally in some normal tissues on the apical surface of cells, but highly expressed in ovarian cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does not modify its expression in ovarian cancer cells, and its expression appears to be mostly associated with a poor prognosis and platinum resistance. Vintafolide is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation of the drug into the cytoplasm of cancerous cells via the FR-α (FR α) and endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to be nontoxic, with moderately adverse events. Phase II clinical trials for the first time demonstrated a statistically significant improvement in disease-free survival in patients with platinum-resistant ovarian cancer, and in those with a very poor prognosis who had already received three to four lines of systemic chemotherapy. The greater benefits were observed in patients with highly expressed FR α.Conclusion: Vintafolide is a promising targeted agent for recurrent platinum-resistant ovarian cancer, first, thanks to its mechanism of action and the characteristics of FRa in ovarian cancer, and, second, because of the favorable results observed in the first clinical trials on platinum-resistant ovarian cancer. Phase III clinical trials are currently ongoing and are expected to confirm these results.Keyword: folate receptor, platinum-resistant ovarian cancer, chemotherapy

We report a case of non-puerperal uterine inversion, illustrating the correlation between MRI and pre-operation macroscopic images.

Objective: To evaluate the feasibility of hysteroscopic resection (HsR) for primary surgical management of missed abortion. Reproductive outcomes and potential benefit of this technique will be compared to traditional dilatation and curettage (D&C). Design: Retrospective cohort study in two Departments (Gynecology and Obstetrics) of a tertiary medical care center (Canadian Task Force classification II-2). Patients: Women with first trimester missed abortion. Intervention: Two techniques were used for the management of missed abortion: ultrasound-guided dilatation and curettage (D&C) and hysteroscopic resection (HsR). Results: We evaluated 358 patients who underwent primary surgical removal of missed abortion. Hundred seventy three patients have been treated by D&C and 185 underwent HsR. In the HsR group, 110 patients (59.5%) have obtained their pregnancy with in vitro fertilization (IVF) vs. 7 patients (4.0%) in the D&C group which make the HsR population hypofertile in comparison to the D&C population. The intra- and post-operative complication rates are low and comparable. Intrauterine anomalies were diagnosed during the HsR in 10 patients (5.4%) and could be investigated after the intervention as a possible cause of miscarriage. Because of the difference in term of fertility, the reproductive outcomes have been analyzed by multivariate analysis. The hazard ratio of pregnancy at 6 months, adjusted to the factor IVF for D&C compared to HsR is 0.69 [0.49–0.96] (p = 0.026). That could represent a significant benefit in the particular population followed in IVF, but regarding the retrospective analysis, and the very different population in the two groups, it doesn't allow us to draw any evidence based conclusion. Conclusion: Hysteroscopic resection is a feasible and safe procedure for the management of missed abortion that could increase the diagnosis of uterine abnormalities. With all the limitation of the design of our study, our data seems to show a trend to a potential benefit in term of reproductive outcomes for hypofertile patient undergoing IVF treatment.