Zolinza (Merck) shows good response with AML patients

Adding Zolinza (vorinostat), from Merck, a histone deacetylase inhibitor that activates genes to frontline combination therapy for Acute Myeloid Leukemia resulted in an 85 percent remission rate after initial treatment. Seventy five patients in a Phase II study received Zolinza, in addition to the chemotherapy drug cytarabine and idarubicin, an anthracycline antibiotic commonly used as chemotherapy. Zolinza activates suppressed genes by protecting acetyl chemical groups that adhere to histone proteins, which are connected to DNA like beads on a string. Acetylated histones make genes more accessible for transcription, so the drug presumably works by reactivating blocked tumor-suppressing genes. Overall, 57 patients achieved complete remission, and another seven had complete remission with incomplete platelets (CRp), for an overall response rate of 85 percent. Median overall survival was 82 weeks and median event free survival was 47 weeks. Overall response rate for 11 patients with the high-risk Flt-3 ITD mutation was 100 percent, with 10 achieving complete remissions and the other a CRp. Their median overall survival was 91 weeks and median event free survival was 66 weeks. Seventeen patients with -5/-7 cytogenetic alterations fared less well. Accordiong to the lead researcher, Guillermo Garcia-Manero, professor at the Univeristy of Texas MD Anderson's Department of Leukemia, no cardiac toxicities and no excess toxicity related to Zolinza were observed. A new Phase III study testing the drug is now underway.