New Treatments Offered For Lymphoma, Mammary Cancer And Oral Melanoma

Cancer, often described as renegade cells growing out of control, is the leading cause of disease related death in dogs. When a dog is diagnosed with cancer, an owner faces uncertainty about the long-term prognosis. Determining the best course of treatment can be challenging. 

Though Shih Tzu are not commonly listed among breeds considered at high risk for developing cancer, they also are not immune to cancer. Here, we take a look at three canine cancers — lymphoma, mammary cancer and oral melanoma — to provide information and insights about research and new treatments. 

Novel Treatment for Lymphoma 

A new therapy for canine lymphoma that was first used in human medicine offers promise in treating dogs affected by the cancer. The therapy, bone marrow transplantation, uses a dog’s own stem cells to simulate bone marrow function and immune system recovery following radiation to kill cancer cells. 

Lymphoma is one of the five most common tumors in dogs, accounting for up to 24 percent of all canine tumors. The lifetime risk is one in 15 for all dogs. It is classified as a hema topoietic tumor, meaning it starts in the blood, originating from bone marrow derived cells. A tumor that grows in lymph nodes and arises from lymphocytes, or white blood cells that fight disease, lymphoma may interfere with the production of normal blood cells if the tumor infiltrates bone marrow. 

The first bone marrow transplantation (BMT) performed in an academic setting in a dog took place in late 2008 at North Carolina State University Veterinary Teaching Hospital. Though it is too soon to assess the survival rate, 45 dogs have received BMTs at the hospital, the first veterinary academic institution in the world to offer the procedure. 

“It will take another few years to really know the cure rate,” says Steven Suter, V.M.D., Ph.D., DACVIM, assistant professor of oncology at North Carolina State University College of Veterinary Medicine. “A dog most likely will have to be cancer-free two years following treatment to be considered cured. We currently are seeing a survival rate of 45 to 50 percent, but we need more time to determine definitely.” 

Performed for many years in humans diagnosed with lymphoma, leukemia and other life-threatening blood diseases, bone marrow transplantation has boosted survival rates to 85 percent for some cancers. The procedure used in humans is based on protocol developed in dogs. 

“In dogs, we first filter stem cells out of the blood,” Suter explains. “Then, the dog receives radiation to kill the rapidly dividing cancer cells in the body. The harvested stem cells are later transfused back into the dog, where they begin growing and developing. The first sign that the procedure is successful is a rising white blood count.” 

Chemotherapy, with or without radiation, is the mainstay treatment for lymphoma. Chemotherapy induces remission in about 75 percent of dogs, giving them an average of eight to 16 months to live. When signs reappear, another round of chemotherapy achieves a second, shorter remission in about 40 percent of dogs. Fewer than 20 percent of dogs achieve a third remission. Ultimately, chemotherapy is credited with the long-term survival of about 2 percent of dogs. 

“Many of our patients come to us after being on chemotherapy,” Suter says. “People are in a bit of a ‘desperation’ mode since their dog has already relapsed when they find us and learn about bone marrow transplantation.” 

A painless procedure, BMT takes about six hours. Dogs are hospitalized for two weeks while their blood counts are monitored and while waiting for the stem cells to start growing and developing. Not all dogs are candidates for BMTs. Dogs with significant disease, those that relapsed after chemotherapy, and those with other serious illnesses are considered poor candidates. 

Dogs may relapse from four to 18 months following therapy. Suter is optimistic that survival rates may emulate those for humans and average 65 percent or higher. “Dogs with T-cell lymphoma, the type common in Boxers, don’t seem to relapse as commonly as dogs with B-cell lymphoma,” he says. 

Though BMT is a costly procedure for owners to consider, averaging from $13,000 to $16,000, it may not be more than chemotherapy considering that dogs often receive multiple rounds of chemotherapy, which could run from $3,000 to $6,000 based on the number of treatments, Suter says. “BMT certainly carries a great likelihood of survival,” he adds. 

Understanding Mammary Cancer 

The most common cancer in female dogs, mammary cancer occurs mostly in older dogs. Telltale signs consist of a single lump, solid mass or multiple swellings in the mammary gland tissue. Tumors can occur in any of eight to 10 mammary glands, and in 50 percent of cases, more than one growth is observed. The prognosis is poor for most dogs. 

A researcher studying mammary cancer at Texas A&M University College of Veterinary Medicine aims to develop a successful therapeutic intervention. Sakhila Banu, Ph.D., clinical assistant professor, says, “Our work involves identifying the genes that are switched on and switched off in mammary cancer. Some genes with mutations can predispose dogs to mammary cancer. The goal is to identify modulations of these genes and then their signaling pathways.” 

Signaling pathways share key molecules that regulate mammary cancer in a process called cross-talk. Already recognized in human breast cancer, the cross-talk concept provides helpful information that allows researchers to target ways of inhibiting cancer growth. 

“Our research found that two signaling pathways – EGF (epidermal growth factor) and PGE2 (EP2 and EP4) receptors – share key molecules and thus regulate mammary cancer,” Banu explains. “When we inhibited the expression of COX-2, an enzyme, the proteins associated with cancer growth decreased. 

“It is important to identify an alternate pathway to diminish or inhibit the synthesis of PGE2,” Banu continues. “We hope to develop a new chemotherapy for dogs combining agents that inhibit EGFR and COX-2.” 

Evaluation of the role of EGFR and COX-2 pathways represent one of many areas of research that is helping to advance breast cancer therapy in both human and veterinary cancer medicine.

A Vaccine for Oral Melanoma 

An aggressive cancer with a high rate of metastasis, oral melanoma is the most common oral cancer in dogs. Since mouth tumors are not readily noticed by owners, the cancer often goes undiagnosed and untreated until an advanced stage. 

Oral cancer primarily affects middle-aged and older dogs between 8 and 12 years of age. Small-breed dogs have a high incident rate, although Shih Tzu are not considered at high risk even though the cancer does occur in the breed. 

Common treatments are surgery with and without radiation and chemotherapy. Depending on the stage of the cancer, these treatments help to increase survival with varying rates of success. A new canine melanoma vaccine, DNA ONCEPT, is helping dogs with stage 2 or 3 melanoma survive longer. 

The size of a tumor determines the stage of melanoma as follows:

• Stage 1 tumors are less than 2 centimeters
• Stage 2 tumors are from 2 to 4 centimeters
• Stage 3 tumors are 4 centimeters or greater and may include lymph node metastasis
• Stage 4 tumors involve metastasis to other locations, such as the lungs and lymph nodes.

“Participants receiving the canine melanoma vaccine had an increased survival time,” says Barbara Kitchell, D.V.M., Ph.D., DACVIM, professor of oncology and director of the Center for Comparative Oncology at MichiganStateUniversity. “In one study, dogs with advanced disease achieved a median survival time of 389 days.” 

The vaccine is administered into the inner thigh muscle of dogs with a needle-free canine injecting device, Kitchell explains. “The vaccine initially is given every two weeks for four treatments, which is followed by one booster dose every six months. No toxicity was reported, although a temporary, low-grade fever was observed in some dogs.” 

In comparison, survival for dogs that undergo surgery is 18 months for stage 1 cancers, five to six months for stage 2 cancers, and three months for stage 3 cancers. Overall, 35 percent of dogs receiving the vaccine survive more than one year. The median survival for untreated dogs is 65 days, based on tumor size, location and recurrence of melanoma. 

Metastatic disease, particularly to the lungs, is the most common cause of death in dogs with oral melanoma. The cancer has a high potential to spread to lymph nodes in the neck and throat and then move to the lungs. 

Tumors typically occur in the gums, the lining of the cheeks and lips, the hard palate of the mouth and the dorsal surface of the tongue. Common signs are difficulty swallowing (dysphagia), bad breath (halitosis), excessive drooling (ptyalism), bleeding from the mouth and facial swelling. “Patients with advanced disease may experience difficulty breathing due to metastasis to the lungs,” Kitchell says. 

Diagnosis is based on a tissue biopsy. Blood work is taken to determine a dog’s complete blood count and blood chemistry profile, and along with a urinalysis, is used to evaluate health status and determine the staging of the cancer. This is particularly important since many dogs are geriatric and could have simultaneous age-related diseases. 

Additionally, thoracic X-rays and abdominal ultrasounds may be used to help identify whether the cancer has spread. Oncologists also may evaluate lymph nodes with a fine needle biopsy to determine metastasis. Advanced imaging techniques, such as CT and MRI scans, detect whether the tumor has spread to a dog’s bones. These tests help determine the best treatment for individual dogs. 

Even with aggressive surgery to remove a tumor, dogs with advanced oral melanoma live on average less than five months. These dogs also have a 50 percent chance that the cancer will recur following surgery. 

“Since these tumors are extremely invasive even with aggressive surgical measures, complete removal is often not possible,” Kitchell says. “When the tumor cannot be completely removed or has spread to the lymph nodes, then radiation therapy becomes important.” 

Remission rates with radiation therapy are 70 percent in some studies, but tumors can recur, Kitchell notes. Chemotherapy is often used in addition to surgery and/or radiation due to the aggressiveness of tumors, but oral melanoma generally is resistant to chemotherapy. The response rate in dogs with advanced melanoma varies from 8 to 28 percent. 

Though oral melanoma is a difficult cancer to treat using traditional modalities, the canine melanoma vaccine offers hope to owners who long for more time with their beloved dogs. 

Purina appreciates the support of the American Shih Tzu Club and particularly Carlene Synder, chairwoman of the Health, Education and Research Committee, in helping to identify topics for the Purina Pro Club Shih Tzu Update newsletter.