Pilot study of megestrol acetate and hydralazine in gynecologic adenocarcinomas

Background: DNA promoter methylation serves as an alternative to gene mutation in silencing genes. The progesterone receptor, a target for cancer therapy, has been shown to be silenced in this manner. The object of the study was to determine if patients taking hydralazine as a global demethylating agent would have tumor stabilization or response from using sequential megestrol acetate an secondarily whether the tumor would show changes consistent with the demethylation. Materials and Methods: Heavily pretreated women with gynecologic adenocarcinomas were enrolled on an institutional review approved study. Results: Five patients were enrolled on this initial study. Three patients continued therapy beyond the first four week cycle. These patients had progression free intervals of six, seven, and nine months, respectively. All of the evaluable patients had negative staining for progesterone receptor prior to study. All three patients who finished at least one cycle of therapy had repeat biopsies that demonstrated their tumors stained positively for progesterone receptor. Conclusions: In this pilot study, three patients had progression free intervals of ≥ six months and their tumors which previously stained negatively for progesterone receptor stained positively for progesterone receptor after treatment with hydralazie.

Adenocarcinomas; Demethylation; Epigenetic; Progesterone

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