Cytarabine (Cytosine Arabinoside) is an antineoplasitc agent mostly used to treat lymphosarcoma of dogs. It has been shown to cross the blood-brain barrier of normal dogs.7 There are a few reports of its use to treat GME successfully in dogs.7,13,18 The dose recommended is 50 mg/meter squared, subcutaneously, every 12 hours for 2 days every 3 weeks indefinitely.7 The drug causes a nadir in 7-14 days since it is myeolsuppressive. It can cause vomiting, diarrhea and hair loss. Adverse effects are generally rare and myelosuppresion is less than with lomustine. This drug could be used if lomustine was not effective or not tolerated well. The author has used cytarabine at the increased dose of 100 to150 mg/meter squared, subcutaneously, every 12 hours for 2 days every 4 weeks for one year alternated two weeks apart with monthly lomustine as described above. When using cytarabine for the first time the dose should not exceed 100 mg/meter squared. The dose can be increased to 150 mg/meter squared if the 6 days post medication nadir is not below 3,000.
Leflunomide is an immunomodulatory drug that has been shown in to be effective in treating several autoimmune diseases of dogs, including autoimmune CNS disease, that were unresponsive to conventional therapy.15 It is leflunomide’s active metabolite teriflunomide (A77 1726) that seems to cause the immune suppressive effects.15 All the effects of this metabolite are not know, but it is thought that teriflunomide inhibits pyrimidine biosynthesis and inhibits cytokine and growth factor receptor associated tyrosine kinase activity thus inhibiting T and B lymphocyte proliferation and function.15 The effective dose range of leflunomide is 1.5 to 4 mg/kg once a day, but this dose needs to be individually adjusted for each dog base on their teriflunomide blood level measured 24 hours after a dose is given.15 In humans the peak blood level of the active metabolite is obtained 6 to 12 hours after dosing, and the drug has a very long half-life of about 2 weeks.16 Therefore, it can take up to two months to reach full steady-state.16 An initial loading dose could be used to raise the blood level more rapidly, but to date the author has not done this because of the fear of inducing severe, abrupt adverse effects. The primary adverse effects of this drug observed by the author have been thrombocytopenia and hemorrhagic colitis. In humans hepatotoxicity has been reported16 but this has not been reported in dogs so far. The author has used leflunonmide to treat autoimmune CNS disease of dogs by adding it to prednisone, lomustine, cyclosporine and cytarabine combination therapy in the few cases in which relapse occurs each time prednisone therapy has been withdrawn. Blood levels are measured every 2 to 4 weeks after initiating therapy to adjust blood levels into the safe therapeutic range of 20 to 40 mcg/ml of teriflunomide measured by high-pressure liquid chromatography.15 The author has found that a few dogs that have failed conventional therapy for autoimmune CNS disease have been able to be maintained in remission with addition of leflunomide therapy.
Procarbazine is another antineoplastic alkylating agent used to primarily treat lymphosarcoma. It is lipid-soluble and crosses the blood-brain barrier. It is myelosupressive causing thrombocytopenia and leukopenia. It comes as 50 mg capsules that almost always have to be compounded as an oil base, flavored solution for use in dogs.7 It is given orally as 25 to 50 mg/meter squared once a day.7,19 Hemograms are monitored weekly for the first month then monthly thereafter.7 After the first month, if possible, the dose is reduced to every other day unless disease relapse occurs.7 It might be possible to use this drug carefully at the same time lomustine or cytosine arabinoside are given, but this has not been tried to date. |