What’s new in cancer therapy?

Canine oral melanoma treatment

Canine melanoma has been traditionally treated with surgery and/or radiation therapy for the local tumor, surrounding tissues and regional lymph nodes. Canine oral melanoma is extremely resistant to chemotherapy and adjunct chemotherapy may do little to prolong survival. The diagnosis of canine oral melanoma is a devastating diagnosis for owners and veterinarians alike as the survival time of dogs with advanced melanoma (stages II through IV) that are treated only with surgery, radiation and/or chemotherapy is often less than five months.

The recent development and conditional licensure of the canine oral melanoma vaccine manufactured by Merial by the USDA has been a breakthrough in the treatment of this disease and in vaccine cancer therapy. The vaccine uses a DNA plasmid expressing the human tyrosinase gene. Tyrosinase is a protein that is overexpressed on melanoma cells. The human tyrosinase used in this vaccine is different enough from canine tyrosinase to stimulate an immune response but at the same time similar enough to canine tyrosinase that the immune response targets canine melanoma cells which express canine tyrosinase. Basically it stimulates the dogs own immune system to kill melanoma cells which it otherwise would not target as it would see them as part of “self”.

In clinical trials preceding conditional licensure of the vaccine, dogs with stage I disease (tumor <2cm, negative nodes) had a median survival time greater than 939 days (78 months) with 92.8% survival compared with 12-18 months when treated only with standard therapies. Dogs with stage II disease (tumor 2-4 cm, negative nodes) had median survival greater than 908 days with 79% alive at 1 year and 63% alive at two years compared with 6-8 months when treated with standard therapies. Dogs with stage III disease (tumor > 4cm and/or positive nodes) had a median survival time greater than 1,646 days, with 77% alive after 1 year, 65% alive at 2 years compared to median survival times of 3 months when treated with standard therapies (surgery, radiation and chemotherapy). Studies are ongoing to further support the efficacy and safety of the vaccine hence the conditional licensure for use.

The vaccine is indicated for the treatment of dogs with stage II or III oral melanoma and for which local disease control has been achieved (negative local lymph nodes or positive local lymph nodes that have been surgically removed or irradiated). The vaccine does not replace traditional therapies. The vaccine is very safe, with no contraindications for use when used according to label instructions. The vaccine is administered transdermally with a needle-free special injection device in the medial thigh in four doses biweekly followed by a booster every six months thereafter.

In the USA the vaccine is currently only available through a board certified veterinary Oncologist or Internist given the conditional licensure status in the USA. There is no conditional licensure yet in Canada. Merial has approved the Internal Medicine Specialists at CWVS to administer the vaccine to canine oral melanoma patients after an Emergency Drug Release (EDR) application has been approved for the patient by Health Canada. We have been using the vaccine now for over 12 months at our practice.

Should you have a patient with oral melanoma that you think would benefit from this vaccine please refer them to our internal medicine service. Please do not hesitate to contact us if you have questions about the case or costs of the vaccine before referral. We are pleased to be able to offer this new therapy for this aggressive disease.

Canine mast cell disease treatment

Treatment options to date for mast cell disease include surgery, radiation therapy and various combinations of oral or injectable chemotherapy drugs such as vinblastine, lomustine and prednisone.
We are pleased to announce that we are able to offer treatment with Palladia (toceranib phosphate, Pfizer Animal Health) the first FDA-approved antiangiogenic and antiproliferative cancer treatment specifically for dogs. Palladia is a receptor tyrosine kinase inhibitor. Receptor tyrosine kinases are cellular proteins that phosphorylate other proteins that regulate cell growth and differentiation. They are often abnormally activated/mutated in many cancers including canine mast cell tumors. Drugs like Palladia work by blocking the function of tyrosine kinases in cancerous cells which ultimately inhibits tumor growth and leads to cell apoptosis. FDA approval in the USA was obtained in June 2009. Health Canada has not yet approved/licensed Palladia drug for use in this country. We are able to obtain the drug for appropriate cases after obtaining EDR approval from Health Canada.

Palladia is not for use in all cases of canine mast cell disease. It should be considered when the disease has recurred after standard therapies or has failed to respond to standard therapies. It is only for use in dogs with recurrent (either local or distant) or metastatic mast cell disease. It is labeled only for use in grade II or III, recurrent, cutaneous mast cell tumors with or without regional lymph node involvement. Patients must have failed other therapies for mast cell disease: surgery, radiation and chemotherapy (vinblastine, lomustine, prednisone). Patients must be free of any serious concurrent disease. Patients must have measurable mast cell disease to be treated with Palladia. The goal is for dogs to stay on Palladia long-term for tumor control. It is administered in oral form at home by owners.

Like all drugs and similar to chemotherapy drugs, Palladia may cause side effects even at prescribed doses. Serious side effects can occur with or without warning and may in some rare situations result in death. The most commonly observed side effects which may occur in dogs taking Palladia are gastrointestinal (decreased appetite, diarrhea, weight loss, vomiting). Close veterinary monitoring (weekly) initially is mandatory for dogs being treated with Palladia. Clients must be dedicated to vigilantly monitor their pets for adverse side effects and to keeping all appointments and having all required diagnostic testing done on schedule.

Until the drug is licensed in Canada and widely available we are able to provide the drug free of charge through the generosity of Pfizer. Clients are responsible for costs of appointments and the diagnostics required for tumor staging and monitoring of therapy.

If you have canine patients with mast cell disease who you feel would benefit from a specialists opinion on recommended course of therapy for this cancer feel free to contact us or refer them to the Internal Medicine Service at our hospital.

Tatjana K. Mirkovic, BSc, DVM, Dip.ACVIM (Internal Medicine)