Can lomustine replace radiation therapy in treating incompletely excised mast cell tumors?

Untitled Document

Dogs with incompletely excised grade 1 and 2 mast cell tumors that are ineligible for a second surgery may undergo radiation therapy to help prevent recurrence or metastasis. But this form of therapy is expensive, inaccessible to many practitioners, and inappropriate in sensitive areas because it can cause painful skin reactions. Chemotherapy may be a good alternative, and a recent study in the Journal of the American Animal Hospital Association retrospectively analyzed whether lomustine (CCNU), with or without prednisone, is as effective as radiation therapy in this situation. The authors found 12 cases that fit their criteria-grade 2 mast cell tumors with or without metastases, incomplete surgical excision, and lomustine given with or without prednisone within two months of surgery. The median initial lomustine dose was 60 mg/m2 every three weeks. The dosage was decreased or the interval prolonged in some dogs because of neutropenia or increased serum alanine transaminase (ALT) activity, so the median dose intensity was 17 mg/m2/week. Eleven of the dogs received concurrent prednisone (40 mg/m2/day for seven days, then 20 mg/m2 every other day). The median treatment duration was 6.3 months with a median of eight lomustine doses. Three of the dogs did not complete the treatment course because of increased ALT activity.

Overall, lomustine was effective-the one-year progression-free interval was 100%, and the two-year interval was 77%. None of the dogs experienced local recurrence or regional or distant metastases. The treatment was generally well-tolerated-two dogs developed grade 3 neutropenia and three dogs had grade 2 diarrhea, with one of those dogs experiencing concurrent grade 1 vomiting, anorexia, and lethargy. Of concern was lomustine's hepatotoxicity-one dog developed grade 4 hepatotoxicosis and two dogs died of hepatic disease. However, the dogs that died received high cumulative lomustine doses without having their serum ALT activities monitored. No dog in which serum ALT activity was monitored closely developed liver failure. In the authors' practice, lomustine therapy is discontinued or adjusted if the serum ALT activity exceeds 250 IU/L, and treatment length does not exceed 6 months. Although the authors point out that the size of this sample population was small and that lomustine treatment and monitoring guidelines warrant study on a larger scale, they do think lomustine is a good adjuvant therapy for incompletely excised mast cell tumors.  

Hosoya K, Kisseberth WC, Alvarez FJ, et al. Adjuvant CCNU (lomustine) and prednisone chemotherapy for dogs with incompletely excised grade 2 mast cell tumors. J Am Anim Hosp Assoc 2009;45:14-18.

Link to abstract: http://www.jaaha.org/cgi/content/abstract/45/1/14