The FDA has approved the drug toceranib (Palladia), a new medication that interferes with the formation of tumor blood vessels (angiogenesis), for use by veterinarians to treat pet dogs with mast cell cancer. This is the first cancer agent specifically approved for use in dogs. The drug comes in pill form and is expected to be available in early 2010.
According to the Angiogenesis Foundation, there are more than 6 million pet dogs diagnosed with cancer each year in the United States alone. Mast cell tumors are the second most common type of canine cancer. These tumors usually first appear under the skin, but they can also occur as primary tumors in the intestines, liver and spleen. Mast cell tumors are often aggressive, metastasizing to distant organs and lymph nodes, resulting in disseminated disease and death. Prior to toceranib, the standard treatment of dogs with mast cell tumors usually involved surgical excision followed by radiation and/or chemotherapy for metastatic disease. However, dogs with disseminated mast cell cancer rarely survive beyond 6 months after diagnosis, even with aggressive therapy.
Toceranib belongs to a class of cancer agents called tyrosine kinase inhibitors (TKIs)—molecules that bind to cell surface receptors on tumors and their blood vessels to inhibit their growth and spread. Toceranib is designed to target a specific tumor cell receptor called c-Kit, which is mutated in 25-50% of canine mast cell tumors, and two other blood vessel cell receptors involved in tumor angiogenesis, PDGFR and VEGFR1.
The efficacy of toceranib was evaluated in a double-blinded, placebo-controlled study involving 145 dogs with recurrent mast cell tumors with or without lymph node involvement2. Dogs received either toceranib (3.25 mg/kg orally every other day) or placebo tablets. Dogs in the placebo group that experienced disease progression were permitted to receive toceranib. The objective response rate was 37.2% in dogs treated with toceranib, almost 5-fold greater than when compared placebo-treated dogs, with just a 7.9% rate (P=0.0004). Dogs whose tumors tested positive for a c-Kit mutation were twice as likely to respond to toceranib than those without the mutation (60% vs. 31.3%; P=0.0099). When the analysis was modified to include dogs originally in the placebo group, but that were then allowed receive toceranib, the objective response rate increased to 43%. Treatment with toceranib did not significantly compromise quality of life. Dogs that responded to the drug had higher quality of life scores than those that did not.
“This is a major leap forward for veterinary medicine,” said Dr. William Li, President and Medical Director of the Angiogenesis Foundation. “Eighty percent of dog cancers are identical to their human counterparts, so it makes complete sense that the antiangiogenic treatment approach that works in human cancers would also help dogs.”
The Angiogenesis Foundation pioneered the first use of antiangiogenic therapies in canine cancers in 2000. Foundation researchers, working with veterinarians, developed a cocktail of human drugs suitable for dogs. Named the ‘Navy Protocol’ after a Golden Retriever that first received the treatment, the cocktail has been used to treat more than 600 dogs representing 32 breeds with 26 advanced tumor types. Since 1995, the Foundation has been educating veterinarians and pet owners about the principles of angiogenesis and its promise for conquering cancer in dogs and other animals.
“We anticipate the success of toceranib will open new gateways for angiogenesis research to help animals,” said Dr. Li. “Now, man’s best friend can be treated as well as man himself.”
To learn more about angiogenesis in animal health or about the Foundation’s work in veterinary research, contact: firstname.lastname@example.org.