Genome-wide profiling of epigenetic therapy in cervical cancer (2/26/2008)

In a single-arm interventional study, demethylating hydralazine and the histone deacetylase (HADC) inhibitor magnesium valproate were added to cisplatin chemoradiation in International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer treatment to assess their safety and biological effects.

After signing informed consent forms, patients were typed for acetylator phenotype and then treated with hidralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from Day 7 until chemoradiation ended. Response and toxicity were evaluated, as well as global gene expression from biopsies taken at diagnosis and at day 8 of treatment.

Twenty eight patients gave informed consent; 22 were evaluated for toxicity and 18 for response. Treatment was well-tolerated. The most common toxicity was hematological. Mean plasma levels of hydralazine were 159.9 ng/ml for rapid- and 141 ng/ml for slow-acetylators, whereas for valproate this level was 64.5 fentog/ml. A total of 964 genes were significantly up-regulated. The ribosome protein and oxidative phosphorilation pathways had the highest number of up-regulated genes. Increased acetylated p53 was also observed, as well as increased cytochrome oxidase protein content and activity.

Note: This story has been adapted from a news release issued by the European Society for Medical Oncology

Post Comments: