Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome.
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 1 of the 12 individuals rose from 53,500 to 120,000/microl 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.
Koeffler
H Phillip
HP
Division of Hematology/Oncology, Davis 5005, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Aslanian
Noune
N
O'Kelly
James
J
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004872:Ergocalciferols / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D004872:Ergocalciferols; C084656:paricalcitol