J Vet Intern Med 2007;21:121–126

CCNU for the Treatment of Dogs with Histiocytic Sarcoma

Katherine A. Skorupski, Craig A. Clifford, Melissa C. Paoloni, Ana Lara-Garcia, Lisa Barber, Michael S. Kent, Amy K. LeBlanc, Aarti Sabhlok, Elizabeth A. Mauldin, Frances S. Shofer, C. Guillermo Couto, and Karin U. Sørenmo

Background: Histiocytic Sarcoma is an aggressive neoplasm of dendritic cells that carries a grave prognosis. The efficacy of chemotherapy against this disease is unknown. The purpose of this study was to determine the efficacy of 1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea (CCNU) in dogs with incompletely resected or metastatic histiocytic sarcoma, to describe the clinical characteristics of these dogs, and to identify factors affecting prognosis.

Hypothesis: Our hypothesis is that CCNU has activity against canine histiocytic sarcoma and can improve survival in dogs with advanced disease.

Animals: Included in analysis are dogs diagnosed with histiocytic sarcoma who had gross measurable or residual microscopic disease and who received CCNU.

Methods: A multi-institutional, retrospective, single-arm cohort study was conducted.

Available biopsy samples were tested with an antibody against CD18 when possible to confirm the diagnosis of histiocytic sarcoma.

Results: Fifty-nine dogs were treated at 8 institutions. Twenty-three tumor specimens were confirmed to be CD18 positive. Treatment with CCNU at 60 to 90 mg/m2 resulted in an overall response rate of 46% in the 56 dogs with gross measurable disease. All 3 dogs with minimal residual disease experienced tumor relapse but lived 433 days or more after starting CCNU. The median survival of all 59 dogs was 106 days. Thrombocytopenia (<100,000 platelets/µL) and hypoalbuminemia were found to be negatively associated with prognosis and were predictive of <1 month survival>

Conclusions and Clinical Importance: Results suggest that CCNU is active against canine histiocytic sarcoma and may be useful in the treatment of dogs without negative prognostic factors.

Key words: CD18, Dendritic cell neoplasia, Lomustine, Malignant histiocytosis