June 16, 2009
Oncologists express high hopes for Pfizer’s newly approved Palladia
First FDA-approved canine cancer drug to hit market in early 2010
By: Jennifer Fiala
For The VIN News Service
The U.S. Food and Drug Administration approved the nation’s first drug developed to treat cancer in dogs on June 3, and Pfizer Animal Health plans to soon introduce Palladia tablets (toceranib phosphate) to any boarded specialist who treats oncology cases.
Palladia is approved for treating advanced mast cell tumors in dogs. The current move to soon put it in the hands of veterinary specialists who treat mast-cell tumors is designed to familiarize them with the single-agent therapy and expand the drug’s clinical usage information before it becomes commercially available to all veterinarians in early 2010.
Pfizer is in the process of reaching out to specialists via mail. Pfizer officials expect the drug to be shipped to interested specialists by July 6.
Palladia is not a panacea, but it’s another way to treat cancer, experts say. The drug is indicated to treat Patnaik grade II or III recurrent cutaneous mast cell tumors with or without regional lymph node involvement. It belongs to the tyrosine kinase inhibitor (TKI) class of compounds that works by blocking the activity of key receptors that aid the development of blood vessels that feed tumors, as well as receptors critical for tumor proliferation.
According to a company press release, a clinical safety/efficacy study conducted to license the drug with FDA showed that approximately 60 percent of dogs had their tumors disappear, shrink or stop growing, although experts stress that additional research is needed to confirm those initial results.
“This is exciting,” says Dr. Phil Bergman, chief medical officer for BrightHeart Veterinary Centers. “It’s rationally targeted therapy that’s great to have in our armamentarium.
“These agents have really revolutionized the treatment of cancer in people. This is an important advance in veterinary medicine.”
Bergman, who used Palladia in clinical trials from 2002 to 2006 while head of the Donaldson-Atwood Cancer Clinic at the Animal Medical Center in Manhattan, explains that the drug acts much like medication used to treat gastrointestinal stromal tumor and chronic myelogenous leukemia in humans.
Here’s how it works: Palladia, a small molecule inhibitor, targets two receptor tyrosine kinases (RTKs) that are important for angiogenesis and one that inhibits KIT phosphorylation, which has been implicated in the pathogenesis of cancer.
The clinical safety/efficacy study was double blind, officials say. Parts of the clinical data submitted to FDA were published in the June issue of Clinical Cancer Research. In the published study, 62 of the 153 dogs involved received the drug and the remaining dogs received a placebo. The objective response rate (complete or partial response of tumors) was 37.2 percent compared to 7.9 percent in the placebo group.
“So we had a significant difference in the objective response rate,” says Dr. Amy Trettien, manager of Pfizer’s Veterinary Operations. “We followed the dogs that received placebo, and when the blinding was broken, they could go on Palladia. In those dogs that crossed over — 58 of 63 dogs went on the drug, the objective response rate increased to 42.8 percent with approximately one third of those showing a complete response.
“When you add those that had a stable response rate, the response goes up to close to 60 percent,” Trettien adds.
Dr. Louis-Philippe de Lorimier, a board-certified oncologist and VIN consultant based in Montreal, says he's eagerly anticipating Palladia’s approval in Canada. As of late, he’s been using a “very equivalent” drug known in Europe as Masivet by France-based AB Science, which is in the review process at FDA. If approved, it will be known as Kinavet in the United States.
“It’s funny. We don’t have these drugs, and then, boom — we get a number of them,” he says. “Palladia is a great new tool because it’s more what we call a targeted therapy.
“The mast cell tumors that have the c-KIT mutations are the ones that are bad, and they are the ones that respond best to Palladia,” he adds.
While Palladia is not typical cytotoxic chemotherapy, it is still associated with side effects.
“Typical chemotherapy drugs target rapidly dividing cells and try to affect tumor growth, while Palladia targets specific receptors that effect anti-angiogenesis to target tumor proliferation,” Trettien explains. “But these receptors are throughout the body, so the drug is not free of side effects.”
The most common reported side effects include gastrointestinal issues such as vomiting and diarrhea, black tar-colored feces or blood in vomit or feces. Lack of appetite and bruising are also known side effects.
“GI side effects are common among dogs with advanced mast cell disease, but there was significantly more bloody diarrhea, vomiting and not eating in Palladia-treated dogs,” Trettien says. “In those cases, it’s really important that owners immediately contact their veterinarian. We recommend that these dogs have aggressive treatment for their side effects possibly including a drug interruption. A lower dosage may be required to continue therapy.”
For more on Palladia, visit http://www.vin.com/Link.plx?ID=68427.
VIN News Service commentaries are opinion pieces presenting insights, personal experiences and/or perspectives on topical issues by members of the veterinary community. To submit a commentary for consideration, email firstname.lastname@example.org.
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