Calcitriol is the natural ligand for the vitamin D receptor (VDR) and is a key regulator of bone metabolism and calcium homeostasis. Calcitriol may have antineoplastic activities and may potentiate the antitumor activity of a wide variety of chemotherapeutic agents, steroids, and tyrosine kinase inhibitors. VDRs are expressed in the majority of canine mast cells. This study included an in vitro study and a phase II clinical trial. In the in vitro component of the study, calcitriol suppressed the growth of the canine mast cell tumor cell line (C2) in a dose-dependent manner, as did lomustine (CCNU), vinblastine, imatinib, and toceranib. The dose effect data revealed that concentrations of calcitriol and CCNU, vinblastine, imatinib, or toceranib required for 50% growth inhibition were approximately 2- to 6-fold lower when used in combination than when used alone. In a prospective multicenter center study, a specialized formulation of calcitriol (DN101, Novacea []) at an oral dose of 2.25 mcg/kg body weight once weekly was used to treat dogs with confirmed cutaneous mast cell tumors for 4 treatments in a phase II clinical trial. Dogs were monitored for signs of toxicity via physical examination and serum biochemical panels. Only 10 of 20 dogs were treated with DN101 due to toxicity, and the study was terminated prematurely. Adverse effects included azotemia, severe vomiting, elevated serum calcium, and severe anorexia. High-dose oral calcitriol induced remission in 4 of 10 dogs in this study (complete remission in 1 dog and partial remission in 3 dogs). However, toxicity precluded treatment and study completion.

Commentary: The findings in this study are very encouraging in spite of the calcitriol-associated toxicities. Calcitriol was synergistic with other chemotherapeutic agents in this study, but current usage is limited due to toxicity.—Karen A. Moriello, DVM, Diplomate ACVD

Calcitriol (1,25-dihydroxycholecalciferol) enhances mast cell tumour chemotherapy and receptor tyrosine kinase inhibitor activity in vitro and has single-agent activity against spontaneously occurring canine mast cell tumours. Malone EK, Rassnick KM, Wakshlag JJ, et al. VET COMP ONCOL 8:209-220, 2010.