Background: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy.Hypothesis: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma. Animals: Eighteen dogs with histologically confirmed GI lymphoma. Methods: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases.Results: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22-420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6-700 days). Dogs that failed to achieve a remission (10 versus 117 days; P 5 .002) or had diarrhea at initial presentation (70 versus 700 days; P o .001) had shorter survival times.Conclusion and Clinical Importance: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.

One hundred seventy-nine tumor-bearing dogs were treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) between 1995 and 2001. CCNU was given as a single dose of 50-110 mg/m 2 body surface area PO. Treatment interval varied, but the minimal interval between CCNU doses was 3 weeks. After treatment, 11 dogs (6.1%) developed hepatic toxicity. The median number of CCNU doses and the median total cumulative CCNU dose were significantly higher in dogs that developed hepatic toxicity (4 doses; 350 mg/m 2 ) than in dogs without hepatic damage (3 doses; 230 mg/m 2 ). Median duration to detection of hepatic toxicity from the last dose of CCNU was 11 weeks (range 2-49 weeks). Common biochemical abnormalities were abnormally high serum liver enzyme activities and hypoalbuminemia. Six dogs with CCNU-associated hepatic toxicity had ascites, and 3 dogs had concurrent pleural effusion. Serum concentrations of bile acids were abnormally high in 4 of 5 dogs tested. Percutaneous ultrasound-guided liver biopsies were performed in 10 dogs, and findings were nonspecific and chronic in nature. Seven dogs were euthanized because of progressive liver failure, and their median survival from diagnosis of liver disease was 9 weeks. Three dogs died of other causes and 1 dog of unknown cause. Although clinical signs resolved in 3 dogs, biochemical abnormalities and histopathologic lesions persisted 4 to 38 months from the time of diagnosis of liver disease. Our findings suggest that CCNU can cause delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and can be fatal.

A chemotherapy protocol using a consolidation phase of alkylating agents was used for treating 94 dogs with lymphoma. Fifty-seven percent of dogs were in stage V, 63% were ill and 38% had T-cell lymphoma. The complete remission (CR) rate was 70% and is comparable to results achieved with previously published chemotherapy protocols. Anorexia predicted the remission; of the 40 dogs without anorexia, 35 (88%) achieved CR whereas of 52 dogs with anorexia, 30 (58%) achieved CR. Median first CR duration was 168 days and 1- and 2-year CR rates were 17.4 and 15.5%, respectively. Platelet count affected length of first CR, with a 53.2% reduced chance of coming out of remission with each log increase in platelet count. Median survival time was 302 days. One and 2-year survival rates were 44 and 13%, respectively. Anorexia and no dose reduction of any drug were independent negative variables. Of 93 dogs with toxicity data, 65 dogs (70%) required a dose reduction. Cyclophosphamide was most commonly reduced with reductions in 31 (38%) of 82 dogs. A dose reduction was significantly more likely in dogs with B-cell lymphoma than in those with T-cell lymphoma.