BACKGROUND: Activation of the KIT receptor tyrosine kinase is associated with the development of canine mast cell tumors (MCT). HYPOTHESIS/ OBJECTIVE: To evaluate the efficacy of masitinib, a potent and selective inhibitor of KIT, in the treatment of canine MCT. ANIMALS: Two hundred and two client-owned dogs with nonmetastatic recurrent or nonresectable grade II or III MCT. METHODS: Double-blind, randomized, placebo-controlled phase III clinical trial. Dogs were administered masitinib (12.5 mg/kg/d PO) or a placebo. Time-to-tumor progression (TTP), overall survival, objective response at 6 months, and toxicity were assessed. RESULTS: Masitinib increased overall TTP compared with placebo from 75 to 118 days (P = .038). This effect was more pronounced when masitinib was used as first-line therapy, with an increase in the median TTP from 75 to 253 days (P = .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P = .009]) or wild-type KIT (66 versus 253 [P = .008]). Masitinib was generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or vomiting as the most common adverse events. CONCLUSIONS AND CLINICAL IMPORTANCE: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.
BACKGROUND: Activation of the KIT receptor tyrosine kinase is associated with the development of caninemast cell tumors (MCT). HYPOTHESIS/ OBJECTIVE: To evaluate the efficacy of masitinib, a potent and selective inhibitor of KIT, in the treatment of canine MCT. ANIMALS: Two hundred and two client-owned dogs with nonmetastatic recurrent or nonresectable grade II or III MCT. METHODS: Double-blind, randomized, placebo-controlled phase III clinical trial. Dogs were administered masitinib (12.5 mg/kg/d PO) or a placebo. Time-to-tumor progression (TTP), overall survival, objective response at 6 months, and toxicity were assessed. RESULTS:Masitinib increased overall TTP compared with placebo from 75 to 118 days (P = .038). This effect was more pronounced when masitinib was used as first-line therapy, with an increase in the median TTP from 75 to 253 days (P = .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P = .009]) or wild-type KIT (66 versus 253 [P = .008]). Masitinib was generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or vomiting as the most common adverse events. CONCLUSIONS AND CLINICAL IMPORTANCE: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.
Authors: D M Vail; H von Euler; A W Rusk; L Barber; C Clifford; R Elmslie; L Fulton; J Hirschberger; M Klein; C London; M Martano; E A McNiel; J S Morris; N Northrup; B Phillips; G Polton; G Post; M Rosenberg; D Ruslander; A Sahora; S Siegel; D Thamm; S Westberg; J Winter; C Khanna Journal: J Vet Intern Med Date: 2012-03-06 Impact factor: 3.333
Authors: Patrice Dubreuil; Sébastien Letard; Marco Ciufolini; Laurent Gros; Martine Humbert; Nathalie Castéran; Laurence Borge; Bérengère Hajem; Anne Lermet; Wolfgang Sippl; Edwige Voisset; Michel Arock; Christian Auclair; Phillip S Leventhal; Colin D Mansfield; Alain Moussy; Olivier Hermine Journal: PLoS One Date: 2009-09-30 Impact factor: 3.240