Hemolytic anemia in two patients with glioblastoma multiforme: A possible interaction between vorinostat and dapsone

We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone. There are several potential mechanisms by which histone deacetylase inhibition may alter dapsone metabolism including changes in hepatic acetylation or N-glucuronidation leading to an increase in the bioavailability of dapsone’s hematotoxic metabolites. In addition, vorinostat may lead to increased hemolysis through inhibition of heat shock protein-90, a chaperone protein that maintains the integrity of the red blood cell membrane cytoskeleton. The potential interaction between dapsone and vorinostat may have important clinical implications as more than 10 clinical trials evaluating drug combinations with vorinostat in patients with malignant glioma are either ongoing or planned in North America.

Source: Journal of Oncology Pharmacy Practice - May 5, 2015 Category: Cancer & Oncology Authors: Lewis, J. A., Petty, W. J., Harmon, M., Peacock, J. E., Valente, K., Owen, J., Pirmohamed, M., Lesser, G. J. Tags: Case Reports Source Type: research