CCNU for the Treatment of Dogs with Histiocytic Sarcoma

Abstract

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/m 2 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/mL) 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.

Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcoma

“…Historically, the majority of dogs with HS have disseminated disease at the time of initial examination, with reported metastatic rates of 70% to 91%. [3][4][5]7 Our findings are similar, and in both the PAHS and non-PAHS groups, nearly 70% of dogs were suspected to have metastatic disease. Despite the presence of metastatic disease, outcome may be improved when patients are treated with surgery, radiation, chemotherapy, or a combination of these.…”

“…The concurrent administration of prednisone may be a negative predictive factor for survival time and TTP in dogs with PAHS. In dogs, HS is typically associated with high metastatic potential and grave prognosis, [2][3][4]7 and previous reports 3,4,6 have encouraged the use of aggressive multimodal treatment to improve outcome. Recently, the MST for dogs with LHS in which tumors were reduced to microscopic disease with definitive local treatment followed by adjuvant lomustine was reported 6 to be approximately 19 months.…”

“…In the presence of gross evidence of disease, 46% of dogs with HS achieved a response to treatment, and the reported MST for responders was 172 days. 7 In a series 4 of 37 FlatCoated Retrievers with HS, the overall response rate of dogs receiving lomustine was 66.7%. The majority of dogs in that series had HS arising near an appendicular joint.…”

“…Previous reports 4,7 evaluating HS in dogs identify anemia, thrombocytopenia, splenic involvement, hypoalbuminemia, and the presence of metastatic disease at diagnosis as predictors of patient outcome. In univariate analysis, 2 factors were associated with a poorer prognosis when evaluating dogs with PAHS in the present study.…”

“…2 Despite reported metastatic rates of 70% to 91%, treatment consisting of surgery, radiation, chemotherapy, or a combination of these appears to improve outcome in dogs with HS. 3,4 In a recent study 7 of 59 dogs with gross or disseminated disease, 54% of dogs that lived longer than 7 days following the first treatment with lomustine achieved either a partial or complete response, and the patients that responded experienced an MST of 5.5 months. In a series 4 of 37 Flat-Coated Retrievers with LHS, the presence of distant metastasis at diagnosis was a strong negative predictor of survival time.…”