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: vetmed@angio.org.
By
Roderick Smith, M.S.
References: Khanna C, Gordon I. Catching cancer by the tail: New perspectives on the use of kinase inhibitors. Clin Cancer Res 2009;15(11):3645-3647.
London CA, Malpas PB, Wood-Follis SL, et al. Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res 2009;15(11):3856-3865.
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