Mike Kiselow, DVM, DACVIM (Oncology) – Campbell
Pfizer Animal Health recently announced the approval of Palladia (toceranib phosphate) by the Food and Drug Administration. Palladia represents the first antineoplastic agent developed and manufactured specifically for dogs, and is indicated for the treatment of grade II or III recurrent cutaneous mast cell tumors, with or without regional lymph node metastasis.
Palladia belongs to the category of antineoplastic agents known as small molecule inhibitors, and it specifically targets a class of cell receptors known as tyrosine kinases (RTK). This class of medications is well-established in human oncology and currently represents an intense area of laboratory and clinical research. Specifically, Palladia inhibits the RTK known as c-kit, which is mutable and contributes to the development of mast cell tumors in dogs. In addition, Palladia inhibits other RTKs (VEGF, PDGF) which are normally involved in angiogenesis. Therefore, Palladia’s mechanism of action also involves antiangiogenic effects against tumor tissues.
Palladia is an oral medication that is given chronically on an every-other-day schedule. Field efficacy studies indicate that Palladia is fairlywell tolerated by dogs. Nevertheless, side effects have been documented, and patients need to be monitored very carefully when undergoing treatment in order to avoid severe toxicity. The most common adverse effects reported include gastrointestinal disturbance (anorexia, vomiting, diarrhea), as well as neutropenia and lethargy. Less common toxicities include musculoskeletal abnormalities and hemorrhagic diarrhea. It is absolutely imperative that these side effects are identified early and managed aggressively with supportive medications and adjustments to dosing regimens. In an effort to continue expanding our understanding of adverse reactions to Palladia, Pfizer recommends a rigorous follow-up schedule for treated patients. This consists of weekly exams and bloodwork, as well as careful recording of history from pet owners.
Palladia has shown moderate efficacy against mast cell tumors in dogs. In a study of 151 dogs with macroscopic mast cell tumors1, 37.2% experienced a measurable response to therapy. A total of 60% experienced either measurable reduction in tumor size or stabilization of tumor growth. To date, Palladia has not been used in combination with other chemotherapy agents to determine if a superior effect can be achieved.
Mast cell tumors represent a diverse range of disease, and overall have shown only modest response to chemotherapy. While Palladia represents an outstanding breakthrough in research and an important addition to available therapeutic options, indications for its use must be decided on a case-by-case basis. It is imperative that patients be examined individually to determine if they are appropriate candidates for therapy in order to avoid the risk of severe side effects. Also, as with other chemotherapy medications, Palladia should not be considered a routine substitution for previously proven effective, conventional treatments for mast cell tumors such as surgery and radiation therapy.
Palladia is not yet available for universal use, but has recently been dispensed in small amounts to veterinary oncologists. If you have any questions about Palladia, do not hesitate to contact a VMS oncologist.