the objective response rate in Palladia treated dogs was 37.2% versus 7.9% in placebo treated dogs. Of Recentin 58 dogs that received Palladia after placebo escape, 41.4% experienced an objective response. The overall objective response rate for all 145 dogs receiving Palladia was 42.8%. As expected, dogs with Kit mutations were much more likely to respond to Palladia than those without Kit mutations. Also, those dogs without lymph node metastasis had a higher response rate than those with lymph node involvement. epigallocatechin (-)-Epigallocatechin gallate Interestingly, tumor grade did not affect the likelihood of response to therapy, although it did impact the time to progression, with grade III MCTs failing earlier than grade II MCTs. These data confirmed that Palladia has biologic activity against canine MCTs and suggests that the addition of Palladia to MCT treatment regimens may improve overall outcome.
Kinavet Kinavet is another TKI that primarily targets Kit and Rivaroxaban Factor Xa inhibitor possibly PDGFR as well. An open label phase II study of Kinavet was completed in dogs with grade II and III MCTs. Of 13 dogs treated, there were 2 complete responses, 2 partial responses, and stable diseases in an additional 2 dogs, the drug was well tolerated. Subsequent to this study, a randomized, double blind, placebo controlled phase III clinical trial of Kinavet was performed in more than 200 dogs with nonmetastatic grade II or III MCTs.69 Although the overall response rate was not significantly different between placebo and Kinavet treated dogs, there was a significant difference in time to progression between the 2 groups, suggesting that Kinavet has biologic activity inMCTs.
Although dogs with MCTs possessing Kit mutations did not experience a significantly Nilotinib 641571-10-0 greater response to therapy when treated with Kinavet compared with placebo, they did experience a significantly longer time to progression. This was more pronounced in dogs with MCTs possessing Kit mutations. These data support the notion that the biologic activity of Kit inhibitors is greatest in the setting of activating mutations. Gleevec Gleevec has been used in dogs primarily to treat canine MCTs. However, it is known to induce hepatotoxicity in a proportion of dogs, this hepatotoxicity appears to be idiosyncratic in nature, resulting in elevations in ALT and ALP that necessitate discontinuation of therapy.
A recent study demonstrated some response to therapy in 10/21 dogs treated with Gleevec, the objective response rate was 100% in dogs whose MCTs possessed a Kit ITD.70 No dogs were observed to exhibit hepatotoxicity, although Africa the duration of treatment was relatively short in most patients because several owners elected discontinuation of therapy because of cost. Another study reported partial responses to therapy in 3 dogs with systemic mast cell disease treated with Gleevec.71 Two dogs survived for 117 and 159 days, and the third was alive after 75 days, no Gleevec induced hepatotoxicity was noted in these 3 dogs. Although Gleevec may induce hepatotoxicity in dogs, it is apparently well tolerated in cats. A phase I clinical trial evaluating the toxicity of Gleevec was performed in 9 cats with a variety of tumors.72 Doses of 10 to 15 mg/kg were well tolerated with no evidence of hematologic toxicity and only mild gastrointestinal toxicity.