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.
Calcitriol potentiates the effect of multiple chemotherapy agents in a variety of tumour models. In this study, we examine whether calcitriol increases chemotherapy or tyrosine kinase inhibitor in vitro cytotoxicity in canine mastocytoma C2 cells. We also evaluate the in vivo effect of DN101, a highly concentrated oral formulation of calcitriol designed specifically for cancer therapy, as a single-agent therapy in dogs with mast cell tumours (MCTs). Calcitriol exhibits synergistic, antiproliferative activity when used in combination with CCNU, vinblastine, imatinib or toceranib in vitro. The concentrations required for 50% growth inhibition were generally two- to six-fold lower when the drugs were used in combination than when used individually. High-dose oral calcitriol induced remission in 4 of 10 dogs (one complete remission, three partial remissions), although the majority experienced toxicity, necessitating discontinuation of the trial. Further evaluation of calcitriol in combination therapy for dogs with MCTs is warranted.
Malone
E K
EK
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Rassnick
K M
KM
Wakshlag
J J
JJ
Russell
D S
DS
Al-Sarraf
R
R
Ruslander
D M
DM
Johnson
C S
CS
Trump
D L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D015153:Blotting, Western / Q000662:veterinary; D002117:Calcitriol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D000068877:Imatinib Mesylate; D007211:Indoles / Q000494:pharmacology; D008130:Lomustine / Q000494:pharmacology; D008297:Male; D034801:Mastocytoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000032:analysis; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D016896:Treatment Outcome; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D001549:Benzamides; D002120:Calcium Channel Agonists; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D018167:Receptors, Calcitriol; C464577:toceranib phosphate; D014747:Vinblastine; D008130:Lomustine; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D002117:Calcitriol