M. Pereira; E. Maubecin; M. Fidanza; G. Mira; A. Marquez
The purpose of this study was to report the experience in use of Lomustine as agent rescue in canine lymphoma.
Lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea [CCNU]) is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Because this drug generally is not cross-resistant with other alkylating agents and is not associated with multiple drug resistance, can be effective for use in relapsed and refractory cases of canine lymphoma.
Lomustine is administrated orally in dose of 80-100mg/m2 every 3 or 6 weeks. This drug is completely absorbed in 30-60 minutes, metabolized by liver and their metabolites excreted by kidney. Gastrointestinal effects as vomiting may occur 45 minutes to 6 hours after administration and usually abates within 24 hours. This quimioterapic agent produce myelosuppression (neutropenia and thrombocytopenia) which is cumulative and nadir occur 1 or 4 weeks after treatment and can produce pulmonary toxicity with dyspnea, tachypnea, and nonproductive cough. Lomustine affect the metabolism of hepatocytes causing the transient enzyme elevation. Nephrotoxicity can be observed after months of treatment. Dermatologic and neurologic effects are a rare complication of treatment with Lomustine.
Nine canine patients with lymphoma, from the Teaching Hospital of the School of Veterinary Sciences-UBA, that had relapsed or had been refractory to the chemotherapy, were treated with lomustine at a dosage of 90mg/m2 body surface area p.o. every 3 weeks. Peripheral blood cell counts was monitored weekly during the treatment. Liver and renal function and pulmonary radiological pattern were evaluated prior to each therapy.
Complete or partial responses occurred in seven of nine cases. Two canines (28,5%) had long survival time for a median of 150 days and five remaining cases (71,5%) had short survival time for a median of 65 days. Neutropenia and thrombocytopenia were observed in all patients 7-10 days after administration. Myelosuppression is cumulative after repeated courses of treatment, and a dose interval of 3 weeks may be too short for continued treatment of this drug. A transient elevation of hepatic enzymes were observed in all cases.
Evidence of pulmonary fibrosis was observed in two cases (28,5%) which received 4 or more treatment. Gastrointestinal and neurologic signs or renal damage weren't observed. CCNU is effective in the treatment of relapsed and refractory cases of canine lymphoma, although requires more clinical trial.