Tolerability of metronomic administration of lomustine in dogs with cancer.

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 (2.84 mg/m² PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death.

RESULTS

Starting dosage (median) was 2.84 mg/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.