Cancer Treatment Update

Dr. Rowan Milner, BVSc, MedVet
University of Florida

Introduction
Veterinary oncology is undergoing fundamental change. The old paradigm of if it can’t be surgically removed then euthanasia is the next step no longer applies. The reason for this change is due to the following factors: pet owners are becoming more sophisticated in their requirements for specialized treatment, improved results due to better treatment protocols and drugs, a heightened awareness in private practitioner of the early signs of neoplasia leads to earlier detection of cancer leading to more successful treatment, and an increase in age of the pet population has lead to a population of pets with a greater risk of developing cancer.
A very important consideration in veterinary oncology is client counseling. Cancer has a very emotional connotation and requires tact and patience in giving bad news to the owner. In the medical field, physicians are taught to steer the middle course by using language that would dispel ignorance without dispelling hope. Veterinarians need to communicate clearly the options available to the owner. A recent report on people’s response to bad news cited most respondents as retaining only about 15 percent of what was told to them on the first visit. It is therefore imperative to supply literature and information to owners about their pets’ cancers that can be read at a leisurely pace.
Veterinary oncology has learned a tremendous amount from the human experience, however there are some major differences. In animals, cure is often not a realistic goal but rather quality of life, and therefore when chemotherapy is used drug dosages are lower.
As a result, they do not experience the same side effects associated with chemotherapy in man.
However, complications associated with treatment do occur, e.g. drug induced pancreatitis, and bone marrow suppression.

Cancer is essentially a genetic disease. Two of the most important discoveries have been the identification of genes called oncogenes (onco meaning cancer) and cancer suppressor genes.
Oncogenes exist in the normal cell but when cancer occurs, depending on the cause, these genes are modified. These genes are involved in regulating cell activity, e.g. growth and protein production, and when changed uncontrolled growth occurs. Cancer suppressor genes on the other hand, act to suppress uncontrolled cell growth. When they are changed cells develop immortality.The normal check and balances that determine if a cell should divide are lost. It is worth noting that unlike oncogenes, cancer suppressor genes may be found in germ cells, allowing the defect to be passed from one generation to the next. It has become clear that no single gene is responsible for the transformation of a cell, but rather two or more oncogenes as well as cancer suppressor genes are needed.

There are also a number of pathways that may be involved in the generation of a particular cancer. These are via: heritable carcinogenesis, passive carcinogenesis, chemical carcinogenesis and physical carcinogens. Cancers are a collection of cells that are always changing. This phenomenon is termed cancer progression. Cancer progression generally results in disease that is more aggressive. This may partly explain the poor prognosis of cancers that are detected late.

The major distinguishing feature between benign or malignant cancers is the ability of malignant cancers to spread to distant sites.

Clinical Staging
Staging is the process of investigating and documenting the extension of a cancer within the body. This is achieved by physical examination, X-rays, ultrasound, CT, nuclear medicine MRI and biopsy.

Treatment of Cancers
Cancers are treated in several ways depending on their position, malignancy and tissue type.
Most solid cancers are treated using surgery followed by chemotherapy and/or radiation.

Chemotherapy
Other than for cancers arising from immune system and bone marrow, chemotherapy is employed in combination with other treatment options (e.g. radiation and/or surgery).
Chemotherapy’s main function in these cases is to mop up leftover cancer cells or to suppress distant metastases. Few chemotherapeutic agents are without side effects and in some cases these toxicities are life threatening. Resistance to treatment, as is seen with antibiotic resistance, also occurs with chemotherapy and leads to therapy failure.

Radiation Therapy
Radiation therapy involves the treatment of cancers with radiation delivered by way of either modified X-ray machines (orthovoltage or linear accelerators) or radioactive sources such as cobalt-60. Radiation therapy works by causing free radicals (reactive molecules), which then damage the cells DNA. Cells then die when they reach the stage of wanting to divide. This process is dependent on the susceptibility of the tissue and the presence of oxygen. Typically, tissue such as brain is resistant to the effects of radiation since the cells are not dividing whereas bone marrow cells are very susceptible due to their rapid division.

Surgery
This is the oldest method and still the most effective of treating cancer in the early stage.
Surgical techniques are advancing all the time, which enable veterinary oncologists to achieve the ultimate goal of cure. In most cases of malignant cancer, surgery forms part of the therapy that may include chemotherapy and radiation.

Nutrition
Nutrition is probably the most neglected part of therapy for cancer. Research has shown that there are substantial changes in the metabolism of fats, carbohydrates and protein that occur in a patient with cancer. A specific cancer diet has been formulated by Hills known as n/d. This diet contains high levels of essential fatty acids (FFA) in the form of omega-3 FFA (fish oil is high in omega-3). Omega-3 has been shown to aid in the reversal of the metabolic changes seen with cancer. This diet also has reduced levels of carbohydrate, the reason for this is that cancers prefer sugars to metabolize and produce less energy from this metabolism. The body has to then convert the lactic acid from this cancer metabolism back to a usable fuel for cells at a net loss of energy to the body. Correct nutrition in cancers will starve the cancer of nutrients and thereby aid in the treatment.

Alternative
Alternative therapy covers all the aspects, from herbal remedies to acupuncture. While these therapies may be beneficial, the vast majority of them have not been subjected to close scientific scrutiny. The use of antioxidants are beneficial in preventing cancers, however, they may be contraindicated during therapy. The reason for this is that most drug and radiation therapy for cancer work via the production of oxidants (free radicals) and concurrent use of antioxidants may cause the drugs to work sub optimally.

When we evaluate the effectiveness of therapy, we use the following terminology. The terms used by definition are:

  • Complete Response (CR): Disappearance of all cancer in all sites for a defined period of time.
  • Partial Response (PR): Decrease in size of all cancers by 50 percent or greater as measured by the sum of the products of two diameters for each cancer. There should be sustained decrease in cancer size, as defined for CR, and no new cancers should arise.
  • Stable Disease (SD): Decrease of 50 percent or an increase of 25 percent in the sum of the products of the diameters as measured for PR.
  • Progressive Disease (PD): Increase of 25 percent or more in the sum of the products of cancer diameters or the appearance of a new cancer.Note: It should be remembered that remission does not necessarily mean cure but rather the disappearance of clinically detectable disease.
  • Common Cancer TypesLymphoma in Dogs:
    Dogs with lymphoma (cancer of the lymphoid tissue) typically present with enlarged glands, either locally or all external glands. Since the body has lymphoid tissue everywhere, it can occur in any organ. However, the multicentric (all peripheral glands form is the most common). When veterinarians stage lymphoma in the dog, the most important criteria they look for are: extent of the disease (does it involve the spleen and/or liver), whether or not the dog has systemic signs (e.g. weight loss, excess urine production), and type of lymphoid cell involved. These criteria are used to determine the chances for a meaningful response to treatment. Veterinary oncologists will treat most lymphomas as the therapy relieves many of the symptoms of the cancer and response can sometimes be unpredictable.

    Treatment can take various forms depending on the site and extent of the lymphoma. However, chemotherapy remains the mainstay of treatment. Drugs most commonly used are cortisone, alkylating agents and anthracycline antibiotics. Most treatments consist of multiple drugs, although there are single drug treatments. Therapy is divided into an induction period of 4-6 weeks followed by maintenance treatment for 6-24 months. The most effective combination is known as the Wisconsin-Madison protocol. This protocol gives the best remissions and survival times. However, since it has multiple drugs it also has a moderate level of toxicity. The goal of treatment is to achieve a good remission of the cancer. Remission rates vary from three months to as much as 36 months or longer. Generally, a stage III lymphoma with no complications can be expected to remain in remission for 6-9 months followed by re-induction of remission for, on average, another 3-6 months. Cure of canine lymphoma is only rarely achieved.

    Perianal Cancers:
    These are cancers arising around the anus. They are more common in the male dogs than in female dogs. The most common cancers are perianal adenoma (80 percent), followed by adenocarcinoma and anal sac adenocarcinoma (apocrine gland). Perianal adenoma occurs more commonly in intact males and older large breeds of dog. Testosterone secretion from the adrenal glands (with or without Cushing’s) may stimulate perianal adenomas. Treatment includes surgical removal of the mass and castration.
    Perianal adenocarcinoma is also seen in male dogs and metastasizes locally to the regional lymph node. Prognosis is good if the mass is smaller than five centimeters and can be removed completely with surgery. Castration does not make a difference. Anal sac adenocarcinoma (apocrine gland) is a highly malignant cancer with an increased occurrence in old female dogs. The cancer is often associated with increased urine production resulting in increased water intake. This is due to high calcium levels in the blood. Prognosis is generally poor as the cancer shows early spread and is often resistant to treatment.

    Hemangiosarcoma
    Hemangiosarcoma is a highly malignant cancer of the blood vessel wall. It is more common in the dog and occurs in the spleen, right atrium of the heart and skin. Large breeds of dog appear to have a greater incidence with German Shepherd Dogs having the highest incidence. Because this cancer occurs in deep organs, owners are often unaware that their dogs have the tumor until it suddenly ruptures, which leads to bleeding either in the abdomen or around the heart. These dogs commonly present in a shocked state with white gums and abnormal rhythm to the heart.
    Dogs may even die suddenly for no apparent reason. The best instrument to diagnose the presence of the cancer is ultrasound. When hemangiosarcoma occurs in the skin it can be due to sun damage or metastasis from a distant site (e.g. spleen). Therapy for this cancer is generally unrewarding except for the skin (sun-induced) cancer. Average survival following removal of a spleen is three months.

    Mammary Neoplasia
    Mammary cancer in dogs is seen most often in older intact females. There is a clear statistical link between time of spaying a dog in relation to the number of seasons she has had. The earlier she is spayed the less likely she will develop mammary cancer; so much so that there is even a difference between first and subsequent seasons. Typical presentation is, as in humans, a lump that is felt within the mammary gland. Fifty percent of these turn out to be malignant which go on to spread to the local gland and then to the lungs. Treatment is mainly surgical with radiation and chemotherapy in some cases. Surgery invariably means radical mastectomy. In benign tumor lumpectomy can be done.

    Osteosarcoma
    Osteosarcoma is a cancer of the bone-producing cells of the body. It is a highly malignant cancer, which results in destruction of the bone and in most cases early spread to the lungs. It is a particularly painful cancer, as are most bone cancers. The cancer occurs most commonly in giant breeds of dog, although not exclusively. The most common bones affected are the long bones of the limbs with the site on the bone being away from the elbow towards the knee. The current gold standard for treatment is surgical amputation followed by chemotherapy using a drug called carboplatin. The author (University of Florida) is researching alternative therapies in dogs that cannot undergo amputation. Currently two clinical trials are running.

    Mast Cell Cancer (MCT)
    Mast cells occur throughout the body and take part in the inflammatory reaction associated with allergies. They contain histamine and other pro-inflammatory agents. Because of the histamine contained in MCT, these cancers can cause gastric ulceration and acute allergic reactions. Mast cell cancer commonly arises on the skin but can occur elsewhere. When veterinarians stage an MCT, they take into account the following criteria: position on the body, grade of the cancer, how quickly it grew, and the breed. Criteria that carry a poor prognosis are high grade MCT located in the inguinal (groin) area that have grown rapidly. Treatment varies depending on the former criteria but may include at the very least surgery and/or chemotherapy and possible radiation therapy.

    Dog Owners and Breeders Symposium
    July 27, 2002
    University of Florida
    College of Veterinary Medicine