Tolerability of Metronomic Administration of Lomustine in Dogs with Cancer

Abstract

Background: Metronomic chemotherapy with alkylating agents has been shown to suppress tumor angiogenesis and prevent tumor recurrence in some settings. The use of adjuvant lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) administered in a metronomic fashion has not been evaluated in dogs. Hypothesis: Oral metronomic administration of lomustine will be well tolerated in dogs with spontaneously occurring malignant neoplasms. Animals: Eighty-one dogs with naturally occurring primary or metastatic tumors received metronomic administration of lomustine. Methods: Dogs were enrolled prospectively after cytological or histological diagnosis of a tumor that was unresectable, incompletely resected, refractory to chemotherapy, or metastatic. Dogs received once daily lomustine (2.84mg/m2 PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death. Results: Starting dosage (median) was 2.84mg/m2 PO daily and treatment duration was 98 days (median, range, 1-770 days). The drug was discontinued in 22 dogs because of toxicoses. Toxicoses occurred in 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia. Eight dogs developed some degree of azotemia during treatment. Hepatotoxicosis was observed at a median of 265 days in 11 dogs. Thrombocytopenia was identified at a median of 432 days of administration. Conclusions and Clinical Importance: In dogs with metastatic or terminal neoplasms without renal compromise, metronomic administration of lomustine was well tolerated. This can provide a treatment strategy for dogs that do not have other standard-care treatment options, and warrants evaluation in primary therapy. © 2011 by the American College of Veterinary Internal Medicine.