"Elspar (Asparaginase) Chemotherapy" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 2; Number 21; December 12, 2001. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! THIS WEEK'S TUMOR TIDBIT: ELSPAR (ASPARAGINASE) CHEMOTHERAPY SUPPLIER: (Elspar, Merck Sharp & Dohme). CHEMISTRY/STORAGE/STABILITY: contains the enzyme asparagine amidohydrolase, type EC-2, derived from Escherichia coli; white crystalline powder; each vial contains 10,000 I.U. asparaginase and 80 mg of mannitol; readily soluble in water or 0.9% saline; solution is stable under refrigeration for 8 hours; reconstitute with 5 ml 0.9% sodium chloride or water for IV use, 2 ml 0.9% sodium chloride or water for IM use. PHARMACOLOGY: therapy is based on a metabolic defect in which some neoplastic cells but not normal cells are unable to synthesize an adequate amount of asparagine and depend on an exogenous source of asparagine for protein synthesis and survival; L-asparaginase catalyzes the hydrolysis of asparagine to aspartic acid and ammonia; acts predominantly in G1. PHARMACOKINETICS: halflife in dogs 12 to 40 hours; asparagine plasma concentrations remain depressed for 1 to 3 weeks after administration; penetrates into lymph; CSF levels < 1% plasma levels; only trace amounts in urine and bile; < 50% plasma levels achieved by IM versus IV route; oral administration is ineffective. INDICATIONS: For potentially susceptible neoplastic conditions such as canine or feline multicentric or cutaneous lymphoma (usually used in combination with other drugs; rarely used alone but some preliminary studies suggest single agent durable responses). DOSE: Premedicate with diphenhydramine at 1 mg/kg IM; administer asparaginase 15 to 20 minutes later. a) 400 IU/kg SQ or IM (dogs, cats, ferrets, avians) b) 10,000 to 20,000 IU/m2 SQ or IM (dogs, cats, ferrets, avians) CONTRAINDICATIONS: contraindicated in patients demonstrating hypersensitivity to the drug; increased risk of anaphylaxis with repeated dosing; contraindicated in patients with pancreatitis or a history of pancreatitis (monitor serum amylase), fatal acute hemorrhagic pancreatitis reported in a dog. ADVERSE REACTIONS: immunosuppressive, inhibition of B- and T-lymphocyte function; can diminish or abolish the antineoplastic effect of methotrexate if given prior to methotrexate; may interfere with thyroid function tests by decreasing thyroxin binding globulin; embryotoxic and teratogenic in rodents; not mutagenic in Ames microbial mutagen test; urticaria, arthralgia, respiratory distress, acute anaphylaxis, hemorrhagic pancreatitis have been reported in dogs; evidence of hepatotoxicity in most patients, increases in AST, ALT, AP, bilirubin and serum albumin, fatty liver, inhibition of synthesis of clotting factors and antithrombin III; thromboembolism secondary to decreased antithrombin III and plasminogen levels is not uncommon in humans and has been reported in a dog; interferes with activation and/or detoxification of cyclophosphamide, mercaptopurine, vincristine; possible synergy with cytarabine. WHAT DO WE DO AT GULF COAST? We use Elspar in combination with Vincristine and Cytoxan chemotherapy as part of the treatment of dogs, cats, and ferrets with lymphoma. It is also used to re-induce remission in most pets with drug resistant lymphocytic disorders. There is some anecdotal use in mast cell disease. Recently we have found it works synergistically with CCNU (Lomustine) in the management of cutaneous lymphocytic malignancies (epitheliotrophic, nonepitheliotrophic lymphoma, mycosis fungoides). ANY OTHER QUESTIONS ABOUT ELSPAR? Don't hesitate to call or email us at Gulf Coast Veterinary Oncology! We can forward additional info by email if needed. ALL THE BEST, Kevin A. Hahn, DVM, PhD Diplomate ACVIM (Oncology) & Overall Nice Guy Gulf Coast Veterinary Specialists 1111 West Loop South, Suite 150 Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 http://www.gcvs.com mailto:drhahn@gulfcoastvetspec.com