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.Resulsts: Masitinib increased overall TTP compared with placebo from 75 to 118 days (P 5 .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 5 .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P 5 .009]) or wild-type KIT (66 versus 253 [P 5.008]). 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.
Paraffin-embedded, formalin-fixed tissue samples from 145 cats with lymphoma were analyzed for cluster of differentiation 3 (CD3, a surface antigen) immunoreactivity, argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). This information along with signalment, anatomic site, and feline leukemia virus (FeLV) antigen status was used to determine the potential of these indicators to predict response to therapy, remission, and survival times, and to characterize cats with lymphoma in the era of general availability of FeLV testing and vaccination. Alimentary lymphoma, primarily occurring in older, FeLV-negative cats, was the most common site of involvement. Although the majority of tumors from FeLVpositive cats were CD3-immunoreactive, only one half of CD3-immunoreactive tumors occurred in FeLV-positive cats. Median remission duration and survival times were 126 days and 143 days, respectively, for all cats. Measures of tumor cell proliferation (AgNOR frequency and PCNA-LI) and CD3-immunoreactivity were not predictive of outcome. When all prognostic factors were accounted for by multivariate analysis, response to therapy, FeLV status, and clinical substage were predictive of outcome. FeLVnegative cats that achieved a complete response following induction therapy were likely to have durable (ie, >6-month) responses, particularly when doxoruhicin was included in the chemotherapy protocol. However, FeLV-positive cats had significantly shorter remission and survival times with available chemotherapeutic protocols.Key words: AgNOR; Cancer; Feline leukemia virus; PCNA ymphoma (malignant lymphoma, lymphosarcoma) is L the most common malignancy in domestic cats and accounts for approximately one third of all tumors in this species.' Many cats with lymphoma will achieve remission and return to a good quality of life with appropriate therapy; however, predicting which cats will respond to therapy and which will not is a difficult challenge. termined that markers of proliferation (AgNOR frequency and PCNA-LI) and the cluster of differentiation 3 (CD3, a surface antigen) T-cell phenotype are predictors of treatment response in dogs with lymph~rna.~ The purpose of this study was to determine, in a retrospective fashion, AgNOR frequency, CD3 immunophenotype, and PCNA-LI in a large group of cats with lymphoma and determine if their predictive ability holds true in this species. Such assays could provide rapid, clinically relevant information to better educate clients as to the expected response to therapy as well as a means of prospectively tailoring individual treatments in future trials. In addition, many veterinary oncologists have noted an anecdotal change in the relative frequency of anatomic sites for lymphoma in the last 10-15 years, corresponding to the general availability of feline leukemia virus (FeLV) testing and vaccination programs. This study, therefore, also presents signalment and retroviral and anatomic site data on a large population of cats w...
One hundred and fifteen dogs with neoplasms of the lower urinary tract (bladder and/or urethra) were retrospectively evaluated at five referral institutions participating in ongoing studies by the Veterinary Cooperative Oncology Group. Most tumors were malignant (97%) and of epithelial origin (97%). Lower urinary tract tumors were more common in older dogs weighing greater than 10 kg. The following significant (P less than 0.05) statistical associations were found using the University of Guelph hospital population as control; there was no sex predisposition although the female:male ratio was 1.95:1. Neutered dogs were predisposed as were Airedale Terriers, Beagles, and Scottish Terriers, whereas German Shepherds were significantly under-represented among dogs with lower urinary tract tumors. These statistical associations should be interpreted cautiously because of possible demographic differences in hospital populations among the University of Guelph and other cooperating institutions. There were no significant correlations between age, gender, weight, breed, response to therapy, and survival time. Clinical signs were indicative of lower urinary tract disease and included hematuria, stranguria, and pollakiuria. The laboratory data were nonspecific except for urinalysis test results. Hematuria and inflammatory urinary sediments were most commonly reported; neoplastic cells were identified in the urine sediment of 30% of dogs with lower urinary tract tumors. Contrast cystography was a useful noninvasive diagnostic method since 96% of the dogs had a mass or filling defect in the lower urinary tract demonstrated by this technique.(ABSTRACT TRUNCATED AT 250 WORDS)
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