"CCNU (Lomustine)" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 3; Number 5; February 8, 2002. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! ANNOUNCEMENTS 1 - Come Celebrate! We're having a Celebration of Life reception Saturday March 23rd at Gulf Coast Veterinary Oncology from 2-5 pm. Bring a picture of your pet to place in our new display case. Sorry, no pets allowed since we will be celebrating in our Deli. 2 - Free chemotherapy for lymphoma! Beginning April 15th, we will be offering a free chemotherapy trial for dogs diagnosed but previously untreated lymphoma at our Houston Office. 3 - Free chemotherapy for relapse lymphoma! Beginning June 1st, we will be offering a free chemotherapy trial for dogs with previously treated lymphoma at our Houston Office. 4 - Are you an RVT living in the Houston area and want to work for us! Call Dr. Hahn or Ms. Rhonda Dailey (713-693-1166) for more information. Great Benefits, 4 day workweek, travel to a National Meeting every other year, and more! These are exciting times for us at Gulf Coast Veterinary Oncology - Please call us (Drs. King, Hahn, Cerraras, Freeman & Turner) at any time and check our web site regulary for more information! THIS WEEK'S TUMOR TIDBIT: CCNU (LOMUSTINE) OVERVIEW OF WHAT'S IN THE TEXTBOOKS: ? LOMUSTINE (CCNU) is CeeNU (CCNU) manufactured by Bristol-Myers-Squibb from 1-(2- chloroethyl)-3-cyclohexyl-1-nitrosourea. It is a yellow powder soluble in 10% ethanol and relatively insoluble in water. ? PHARMACOLOGY: CCNU alkylates DNA and RNA; is not cross-resistant with other alkylators; inhibits several enzymatic processes via carbamoylation of amino acids in proteins. ? PHARMACOKINETICS: It is high lipid solubile; tissue concentrations are comparable to plasma concentrations 15 minutes after administration; CSF concentrations are > 50% plasma levels; rapidly metabolized in humans, however, metabolites have prolonged halflives (16-48 hours). ? Contraindications: It is contraindicated in patients with severe bone marrow depression. ? Adverse reactions/drug interactions: marked, cumulative, delayed (up to 6 wks) bone marrow suppression seen in humans; the neutrophil nadir in dogs given 90 mg/m2 is 10-14 days post-administration, 4-7 days if 60 mg/m2 is used; it is carcinogenic and teratogenenic in rodents; mutagenic in vitro; causes infertility; nausea and vomiting at high dosages; dose-dependent pulmonary fibrosis (not reported in dogs or cats); hepatotoxicity and nephrotoxicity are rarely reported. ? Dosage and administration: Supplied as 10, 40, and 100 mg capsules. The maximum tolerable dosage in dogs and cats is reported to be 90 mg/m2 every 3 weeks but the incidence of sepsis is high and 60 mg/m2 every 2 weeks is considered acceptable by many. ? Indications: The current indications are for dogs with previously treated but unresponsive lymphoma or mast cell tumor. See the published reports below. OVERVIEW OF WHAT'S IN THE LITERATURE: * J Vet Intern Med 1999 Nov-Dec;13(6):601-5. Treatment of canine mast cell tumors with CCNU (lomustine). Rassnick KM, Moore AS, Williams LE, London CA, Kintzer PP, Engler SJ, Cotter SM. The efficacy and toxicity of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosourea) were evaluated in 23 dogs with measurable mast cell tumors (MCT). Twenty-two dogs had cutaneous MCT and 1 dog had an intranasal MCT Nineteen (83%) dogs had biopsy of their original mass performed and 4 (17%) had aspiration cytology of masses. Of the 19 tumors histologically graded, 1 (5%) neoplasm was classified as grade I, 10 (53%) were grade II, and the remaining 8 (42%) were grade III. Dogs were treated with CCNU at a dosage of 90 mg/m2 body surface area every 3 weeks. Response could be evaluated in 19 dogs. Eight of the 19 dogs (42%) had a measurable response to CCNU. One dog had a durable complete response for 440 days. Seven dogs (37%) had a partial response for a median and mean duration of 77 days and 109 days, respectively (range, 21-254 days). Treatment with CCNU resulted in stable disease in 6 dogs (32%) for a median and mean duration of 78 days and 122 days, respectively (range, 42-347 days) . The acute dose-limit * J Vet Intern Med 1999 Sep-Oct;13(5):395-8. Lomustine (CCNU) for the treatment of resistant lymphoma in dogs. Moore AS, London CA, Wood CA, Williams LE, Cotter SM, L'Heureux DA, Frimberger AE. Forty-three dogs with lymphoma that had relapsed or had failed to achieve complete remission to previous chemotherapy were treated with lomustine (1-(2-chloroethyl)-3- cyclohexyl-1-nitrosourea [CCNU]) at a dosage of 90-100 mg/m2 body surface area p.o. every 3 weeks. Durable complete or partial responses occurred in 11 dogs for a median of 86 days. The acutely dose-limiting toxicosis was neutropenia 7 days after administration, resulting in a recommended dosage of 90 mg/m2. Cumulative thrombocytopenia occurred in dogs receiving continued CCNU treatment, and a dose interval of 3 weeks may be too short for continued administration of this drug. Toxicoses evident as fever or central nervous system signs or renal damage were uncommon or rare. CCNU is effective in the treatment of relapsed lymphoma. SO WHAT DO WE DO AT GULF COAST? * We have found substantial tumor improvement and increased quality of life in dogs and cats when given CCNU as treatment for mycosis fungoides, cutaneous T-cell lymphoma, malignant histiocytosis, mast cell tumor, and lymphoma. * We begin with a dosage of 60 mg/m2 and check a complete blood count weekly. If the neutrophil count is >4000 at 7 days post-administration, the dosage is repeated. If 7 days following the second dosage the neutrophil count is still > 4000, we escalate the dosage and continue checking blood counts until the 7 day neutrophil count is <3000. Our intent is to repeat CCNU every 14 days as long as there is objective tumor response. * In some patients, other concurrent medications (chemotherapy) may be indicated. Always consult with an oncologist. Don't hesitate to call or email us at Gulf Coast Veterinary Oncology! 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