A University of Florida Health patient has become the first person to receive a combination of oral therapies targeted to a specific gene mutation that has dramatically reduced a rare oral tumor called ameloblastoma.
Anthony Woods of St. Petersburg was 10 years old when he was diagnosed with ameloblastoma. Typically, ameloblastoma is not considered cancerous and doesn’t spread to the lymph nodes or through the bloodstream, according to William Mendenhall, M.D., a radiation oncologist at the University of Florida Health Cancer Center who specializes in head and neck cancers. But Woods’ tumor kept recurring. After years of enduring different treatments, Woods is now responding well to this new oral combination treatment. The results were published recently in the Journal of the National Cancer Institute.
From the time he was diagnosed, Woods, now 40, underwent several surgeries, which were sometimes paired with reconstructions of his jaw. When Woods’s tumor recurred and surgery was no longer an option, Mendenhall treated Woods with a high dose of radiation. Six years later the ameloblastoma tumor recurred again in his jaw and neck, but this time also metastasized to Woods’ lungs – an even more rare occurrence in the disease.
“When Woods’ tumor grew back, his doctors were in the midst of trying to treat it when they spotted his bilateral lung metastases,” said Frederic J. Kaye, M.D., a member of the UF Health Cancer Center, medical co-director of the Thoracic Oncology Program and co-director of the UF Health Lung Cancer Center. “At that point, he had limited choices as to what to do. That’s when he showed up in my clinic.”
Kaye and his colleagues analyzed the cancer gene profile of Woods’ disease, and found a gene mutation that made him a candidate for a new type of combination cancer therapy.
“Dr. Kaye was aware of similar treatments for a skin tumor called melanoma but this is not a treatment you would normally think of for someone with ameloblastoma,” Mendenhall said.
Specifically, Woods had a mutation of a gene called BRAF. BRAF is a receptor on the surface of cells in your body that regulates cell growth. When it’s faulty, it can no longer regulate cell growth, causing tumors such as Woods’ ameloblastoma. About half of all ameloblastoma cases are caused by this faulty receptor, said A. Dimitrios Colevas, M.D., an associate professor of medicine at the Stanford University School of Medicine and member of the Stanford Cancer Institute.
Researchers at Stanford, the University of Michigan and the University of Turku in Finland identified the BRAF mutation in ameloblastoma nearly simultaneously in 2014.
Kaye and others knew a cancer drug called dabrafenib was used in cancers such as melanoma to treat the BRAF mutation. It binds specifically to BRAF, turning off the receptor, Colevas said. Colevas said the second drug, trametinib, targets a second receptor, which is higher up on the cellular circuit than BRAF. Targeting them both ensures that the BRAF mutation is shut down at two different points.
“When you add these two inhibitors in melanomas with a BRAF mutation, the tumor reduction rate is better than using one or the other,” Colevas said. “That basis led Dr. Kaye and his colleagues to pursue this dual treatment.”
Kaye said within days of treating Woods with the combination therapy, Woods noticed a reduction of the tumor in his face and jaw. In clinic visits since Woods has started the treatment, Kaye said Woods’ jaw tumor is much smaller, and the tumor in his lungs is no longer detectable on specialized X-ray scans.
“This is the new arena of targeted therapy directed to the mutation,” Kaye said. “Since these treatments are not FDA approved, our clinical trials office had to work hard to navigate the regulatory hurdles to get approval from the pharmaceutical company, the Food and Drug Administration and our Institutional Review Board. It took us months, but we were able to embark on a treatment that was rewarding for the patient.”
Colevas is now working to open a clinical trial to study new patients with ameloblastoma with the hope of improving the outcome and quality of life for new patients undergoing surgery.
Woods said he considers his treatment’s success a combination of medical care and God.
“Every situation I went through with this tumor, it was supposed to go the other way. God had his hands in it the whole time,” Woods said. “The tumor could have gone to my lungs a lot sooner, when I was 17, when I was 18, 20 or 22, when they didn’t have that pill developed. I’ve been having a great response to the pill thus far, so I feel like that’s the blessing.”
Clinical and Radiographic Response With Combined BRAF-Targeted Therapy in Stage 4 Ameloblastoma, Frederic J. Kaye, Alison M. Ivey, Walter E. Drane, William M. Mendenhall and Robert W. Allan, Journal of the National Cancer Institute, doi: 10.1093/jnci/dju378, published 2015.
Source: University of Florida Health