Vitamin D2 analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome

Abstract Myelodysplastic syndrome (MDS) is often a pernicious disorder associated with pancytopenia in the elderly; therapeutic approaches need to balance their toxicities versus the symptoms of the disease. 1,25(OH) 2 -Vitamin-D 3 [1,25(OH) 2 D 3 ] inhibits proliferation and induces differentiation of leukemic cells in vitro. Small clinical trials of 1,25(OH) 2 D 3 have shown modest efficacy in MDS; hypercalcemia prevented the administration of doses that have been shown to be effective in vitro. Paricalcitol [19-nor-1,25(OH) 2 D 2 , Zemplar] has been approved by the FDA for treatment of secondary hyperparathyroidism. This Vitamin D analog is unique because it has little hypercalcemic potential; but in vitro, it has strong anti-leukemic activity. We conducted a clinical trial of oral paricalcitol to 12 MDS patients whose disease varied between an IPSS of low to high. Drug was well-tolerated in all patients. No responses were observed according to international working group (IWG) criteria. However, the platelet count of 1of the 12 individuals rose from 53,500 to 120,000/μl blood over 5 weeks; but the patient succumbed to a fatal fungal infection. In summary, paricalcitol given as a single agent to MDS patients is therapeutically not very efficacious; further trials of the Vitamin D analog should be considered in combination with other approaches.