A Phase II Study of Epigenetic Therapy to Overcome Chemotherapy Resistance in Refractory Solid Tumors

Summary

Chemotherapy resistance, either innate or acquired requires for its development, expression changes on a large number of genes therefore, it has been hypothesized that epigenetic-mediated changes could be the responsible driving force for chemotherapy resistance. Aberrant DNA methylation and histone deacetylation are the main epigenetic alterations hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) may overcome resistance in refractory solid tumors. Patients will be treated with hydralazine and magnesium valproate starting from day -7 until chemotherapy ends which consists on the same pre-study protocol regimen on which patients progressed. Response and toxicity were evaluated. Global DNA methylation and HDAC activity were evaluated in the peripheral blood cells, as well as the plasma levels of valproic acid and hydralazine.

Timeline

Start

2005-09

Primary completion

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Completion

2006-10

Publications

• Candelaria M, Gallardo-Rincon D, Arce C, Cetina L, Aguilar-Ponce JL, Arrieta O, Gonzalez-Fierro A, Chavez-Blanco A, de la Cruz-Hernandez E, Camargo MF, Trejo-Becerril C, Perez-Cardenas E, Perez-Plasencia C, Taja-Chayeb L, Wegman-Ostrosky T, Revilla-Vazquez A, Duenas-Gonzalez A. A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann Oncol. 2007 Sep;18(9):1529-38. doi: 10.1093/annonc/mdm204.

Drugs

Indications