2015 ACVIM Forum Research Abstract Program

This study indicated that GeneScan analysis would be a convenient and accurate method to determine the clonal origin of lymphoid neoplasms in dogs. The purpose of this study was to compare lomustine content in FDA approved and compounded capsules. The a priori acceptance range was 90-110% of the stated capsule content. Capsules were obtained from an FDA approved manufacturer (Next-Source Biotechnology) and 3 national (USA) compounding pharmacies at 10 mg and 40 mg capsules or the nearest available content. Replicates of 5 capsules per source and strength were assessed by validated high pressure liquid chromatography with ultraviolet detection method. Contents of capsules were emptied individually into methanol to yield a stated concentration of 1 mg/mL, vortexed for 30 seconds and sonicated for 10 minutes. The samples were then vortexed, centrifuged and further diluted in 50% methanol to a final stated concentration of 50 lg/mL. The lomustine concentration was determined by comparing to a standard curve in 50% methanol. The FDA approved capsules had 100% of the capsules for both strengths within 90-110% of stated content. Compounder A had 60% and 0% of 11 mg and 42 mg capsules, respectively within 90-110%. Compounder B had 20% and 0% of 10 mg and 40 mg capsules, respectively within 90-110%. Compounder C had 60% and 0% of 7 mg and 48 mg capsules, respectively within 90-110%. All product failures were <90% of stated content. In conclusion, compounded lomustine capsules failed to have the stated amount of drug, but the FDA approved formulation contained the stated amount of drug. The clinical implications of using compounded lomustine may include treatment failures and increased risk of tumor resistance. Alimentary lymphoma is a common neoplasia in cats and systemic chemotherapy is indicated for the treatment. Although most of cats can achieve a complete remission with chemotherapy, relapse can be associated to the multidrug resistance, that occurs with the use of cytotoxic agents or a previous intrinsic cellular resistance, provided by transmembrane proteins that decreases intracellular drug bioavailability. Furthermore, the lung resistance-related protein (LRP) known as the human major vault protein was found to be overexpressed in many chemoresistant primary tumors of different origins, including lymphomas, that did not express ABCB1 (P-gp) The aim of this study was to investigate ABCB1 and LRP expression in cats with alimentary lymphoma. Immunohistochemistry was performed in 16 samples of cats with alimentary lymphoma without previous treatment, using the monoclonal antibodies: mouse anti-P-glycoprotein (C494; Enzo) and mouse anti-LRP (1014; Santa Cruz Biotech). ABCB1 and LRP immunoreactivity were analysed by degree of labeling intensity, between 0 (no expression) to 3 (strong expression). Lymphoma was classified as B cell in 6 cats (one small and 5 large cells) and as T cells in 10 cats (small cells). ABCB1 expression as well as LRP was higher in cats with B cell lymphoma than in T cell lymphoma. The survival time was longer in cats that did not express or had slightly expression of ABCB1, even in B cell lymphoma. The same was not observed for LRP. More studies are necessary to verifiy if ABCB1 expression could be associated with complete or partial response and survival time. Alimentary lymphoma comprises one of the most common neoplasia in cats. Ki-67 antigen is expressed in proliferating cells during all phases of the cell cycle, b