Performing Department
SMALL ANIMAL CLINICAL SCIENCES
Non Technical Summary
Lymphoma is a common, devastating cancer affecting thousands of cats in the United States every year. Combination chemotherapy is the standard of care. Treatment is associated with substantial cost and potential toxicity. L-asparaginase is used in combination with other drugs to treat feline lymphoma. L-asparaginase is a potentially excellent drug because it may impove the response to treatment without additional toxicity. This drug is expensive therefore efficacy needs to be known to justify its use. This work will provide objective data regarding the value of this drug in newly-diagnosed cats with lymphoma. Ultimately this knowledge will help provide optimal care to cats with lymphoma by validating the use of L-asparaginase in this species.
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Goals / Objectives
To evaluate the response of cats with confirmed diagnosis of lymphoma to a single IM injection of L-asparaginase (Elspar, Merck, Sharp & Dohme Inc, West Point, PA) We will also measure plasma amino acid profiles and ammonia levels prior to, 48 hours after, and 1 week after administration of the drug to assess changes in asparagine, aspartic acid, glutamine, and glutamic acid that occur with use of asparaginase in cats.
Project Methods
Fifteen cats with a confirmed diagnosis of lymphoma of any anatomic site with measurable disease and no prior therapy (including glucocorticoids) will be enrolled in this study through the University of Tennessee College of Veterinary Medicine (UT-CVM) clinical oncology service. An assessment of the cat's health using complete blood count, serum chemistry panel, and urinalysis will be performed. A thorough diet history will be obtained from the client for comparison of different diets among studied cats. Routine tumor staging, including thoracic and abdominal imaging and flow cytometric immunophenotyping of the lymphoma, will be performed. A minimum 12 hour fast will be required prior to blood sampling of ammonia and amino acids. Blood will be drawn to measure baseline plasma ammonia, asparagine, aspartic acid, glutamine, and glutamic acid concentrations. A single dose of L-asparaginase will be administered IM. The cat will be reexamined in 2 days for blood sampling
and measurement of amino acid levels. Reevaluation will take place 1 week from drug administration for blood sampling and tumor restaging to assess response to therapy. The following criteria will be used: Complete remission (CR)- 100% regression of measurable lesion(s); Partial remission (PR)- less than 100% but greater than 50% regression of disease, Stable disease (SD)- less than 25% regression and no new lesions, and no response (NR)- indicates no change or growth in size of the lesion(s). To accurately assess response to L-asparaginase, objective measurements of the tumor will be taken before and 7 days after drug therapy using ultrasonography or radiography. We are requesting funds for the evaluation at the end of the 7 day study period as early re-staging is not typically performed in cats with lymphoma. Ammonia concentrations will be measured by the UT-CVM clinical pathology laboratory with normal cat plasma assayed simultaneously as control. Amino acid levels will be measured
with high-performance liquid chromatography (HPLC) by the UT-CVM clinical pharmacology laboratory. Normal cats will be assayed prior to enrollment of clinical cases to allow assay optimization, and the preliminary work will be paid for by departmental funds. We estimate 18 months to enroll 15 cats with lymphoma, and expect to have data suitable for publication within 24 months from the date of funding. L-asparaginase will be considered an effective chemotherapy drug if the overall response assessed 7 days post treatment (combined complete and partial response rates) is greater than or equal to 30%, or that 5 of 15 cats will have a measureable response to L-asparaginase alone. Blood will be sampled to measure the effect of L-asparaginase on serum amino acid concentrations at 2 days and 7 days post-treatment as previously described. At the end of the 7 day study period, cat owners will be offered additional therapy through the UT-CVM oncology service. We will describe any differences
noted in tumor response, ammonia levels, and amino acid profiles among the subtypes of lymphoma identified in the study population