Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, VTS Oncology
A cancer is a tissue mass characterized by persistent, excessive, and disorganized cell growth that is unresponsive to normal control mechanisms. Cancer is a leading cause of death in dogs and cats. Why this happens, in most cases, is not yet known. As a result of improved owner and veterinary care, pets are living much longer and thus are more susceptible to diseases of old age, such as tumors. Compared to people, dogs develop tumors twice as frequently, but cats only half as frequently. If your pet is thought or known to have cancer, a consultation with a veterinarian experienced in oncology can provide you with valuable information regarding treatment options and expectations.
Terms Used in Cancer Medicine:
Tumor: simply means a "swelling," which may or may not represent cancer.
Benign Tumors: have many normal growth characteristics. They do not "spread" or invade other organs. They, may however, compress body organs or tissues by virtue of their size. Surgical removal is usually curative.
Malignant Tumors: often have rapid, irregular growth characteristics. These tumors can invade normal, local tissues, as well as spread to other tissues (especially the liver and lungs). New tumors can grow at these secondary sites, eventually causing the demise of the patient.
Metastasis: the process whereby a tumor spreads to secondary sites. These new tumors are referred to as "metastatic"," or "metastases."
Oncology: refers to the study of tumors, including their biological behavior and treatment.
Remission: denotes a decrease in tumor size (often called "tumor burden") over time. Remission time is the length of time in which the tumor is under control.
Currently, treatment of cancer in animals can often result in fairly lengthy, good quality remission times. That still means that for many types of cancers, their return is inevitable. This fact must be contemplated and discussed before the client and the veterinarian decide to treat an animal for cancer. Having reasonable and accurate expectations will provide a more positive experience for all those involved.
Types of Cancer Treatments
Surgery: surgical removal of tumors is a very common and valuable approach for solid tissue tumors. It can be used for soft tissue as well as for bone tumors. It can sometimes be curative on its own, if the disease process is localized and detected very early.
Radiotherapy: or "radiation" therapy is available at large veterinary institutions such as New England Veterinary Oncology Group (Waltham, Massachusetts), Tufts University School of Veterinary Medicine (North Grafton, Massachusetts) and Angell Memorial Animal Hospital (Boston, Massachusetts). It consists of the use of a radioactive beam to damage and/or kill malignant cells in a localized area. It can offer good quality remission times for many types of tumors, but usually not cure. Animals are surprisingly tolerant of radiation therapy.
Chemotherapy: is the use of certain drugs alone, or in combination to control tumor growth. All of the drugs currently given to animals are human anti-cancer drugs. Fortunately, many of the negative consequences of their use in human medicine are not experienced in veterinary medicine. Chemotherapy and/or surgery are the two most important treatment modalities in veterinary cancer medicine. A combination of therapies may also be indicated in certain cancers. Some cancers require a specific, brief number of treatments, while others requiring ongoing treatment to maintain remission.
CANINE AND FELINE LYMPHOMA
Lymphoma is a malignancy (cancer) arising from the lymphoid tissues involving the immune system as well as any organ. When the malignant cells are present in the patient's bone marrow, causing blood disorders, it is referred to as leukemia. Some patients have multiple sites where the malignant lymphocytes can be found. The patient can be staged (assessed for disease) as follows:
Stage 1: Malignancy involves a single lymph node or single site.
Stage 2: Involvement of a cluster of lymph nodes in a regional area (including a single tumor of the intestinal tract).
Stage 3: Involvement of all peripheral lymph nodes.
Stage 4: Involvement of liver and/or spleen; associated with shorter remissional/survival times.
Stage 5: Involvement of the bone marrow and peripheral blood stream; associated with shorter remissional/survival times. Substages: Lymphoma patients can be subdivided into:
Substage A: Without systemic signs (ie. not ill).
Substage B: With systemic signs (ie. physically ill).
Staging the cancer patient is vital in determining the best treatment and preparing prognostic information.
T-Cell vs. B-Cell Lymphomas
You may see mention of lymphomas and leukemias as being either of a "B-cell" or "T-cell" origin. A patient's biopsy tissue can be further tested by a technique called immunohistochemistry. This determines the type of cell of the immune system that the malignant clone arose from. The treatment options are the same for both types of lymphoma but over large numbers of patients, it has been shown that the T-cell lymphomas are generally more aggressive. Overall, patients with T-cell lymphomas achieve remission as often B-cell lymphoma patients but their remission times can be significantly shorter (though not always).
The word "chemotherapy" usually evokes unpleasant thoughts in most people's minds. We prefer to think of it as "therapy" for a disease, in the same way people take medications for certain illnesses. The ultimate goal of therapy would be to cure the patient of cancer. In most instances at this point in time in veterinary medicine, this goal is not realistic. The goal we do strive for is to control a rapidly progressive disease, prevent spread of the tumor, restore deteriorated function, and provide a good quality of life during the time of remission. The term ÒremissionÓ means a time interval during which there are no outward signs that the patient has cancer. In the case of lymphoma, if the maximum combination protocol is used, it is expected that 80% or more of patients will go into full remission. The average duration of remission is longer than 12 months. Unfortunately, it is impossible to predict which animals will achieve a full remission or for how long. We do know, however, that if no therapy is used, most pets will die from their disease in a few days to a few weeks.
Protocols for Lymphoma
There are many "protocols" or treatment schedules available for canine and feline lymphoma. Unfortunately, there is not one "key" formula as yet that has been proven superior to all others. Most published protocols contain the same or similar class chemotherapy agents, with minor variations on combination agents and timing of treatments. Most veterinary internists and oncologists use the protocols that they are the most familiar with, and that best fit the particular lifestyle and expectations of the client, and well being of the patient. A brief synopsis of treatment categories for feline/canine lymphoma is as follows: These are continually updated as the field of veterinary oncology advances.
Oral Drug Protocols
|Regimen||Relative Risk of
|Prednisone (cortisone)||low||About 2 months||very low|
|Prednisone + Cyclophosphamide||low||About 2-4 months||low|
|Prednisone + Lomustine||low to moderate||About 2-6 months||low to moderate|
Oral Plus Injectable Protocol
|Regimen||Relative Risk of
|COP (cyclophosphamide, prednisone and vincristine or vinblastine||low to moderate||Average 6-12 months||moderate|
|ACOPA (asparaginase, cyclophosphamide, vincristine or vinblastine and adriamycin (doxorubicin)||Moderate to high,
but very individual
|About 1-3 years||high|
|*NOTE: No guarantee of remission times can be made. These are average lengths. The stage of the disease, protocol selected, general health of the animal, and several other factors are only some of the determinants of remission time. The patient may live longer than the actual remission time.|
Selecting a Protocol
As a general rule, combination chemotherapy is superior to single agent chemotherapy. There are several areas of consideration when determining a chemotherapy protocol for an individual patient. These include:
Stage of the patientÕs disease
Willingness/availability of the owner to endure treatment schedule
Response of the patient to the treatment
Care of the cancer patient requires unique skills, expertise, drugs, procedures, philosophies and supportive care. Each area can be discussed in depth to assist you in determining what path will be best for your particular circumstances.
Please recognize that veterinary patients usually have a dynamic course to their disease and treatment. Estimates for treatment costs do not include unexpected illness, diagnostics, treatment, or hospitalization. Our health team will strive to provide you and your pet with compassionate care as you take this journey with us.
What is Life Like for Chemotherapy Patients?
Chances are that you, or someone you know, have experienced chemotherapy for the treatment of cancer. Veterinarians who treat animals for cancer use many of the same chemotherapy agents that human oncologists use. Yet, in many ways the experience for pets seems very different. Why? For one thing, dosages of chemotherapy agents used in animals tend to be much lower than those used in people. Humans are given the highest doses possible, the consequences of which may require bone marrow transplantation, extended hospitalization, and numerous costly medications-all with good cause. However, for veterinary patients, this process would be unacceptable and cost prohibitive for most owners. The general quality of life for many veterinary cancer treatment patients can be surprisingly good and very close to normal. Most of the time they can maintain their normal activities, travel, and have fun with the families that love and care for them.
Most currently used anti-cancer agents do not specifically target cancer cells. Rather, they target and damage or kill rapidly growing cells. For the patient, this means cells lining the stomach and intestine (high turnover rate), cells of the bone marrow that make up the immune system (white blood cells, in particular), and cancer cells. It then is little surprise that the most common side effects of chemotherapy agents include mild to moderate nausea, vomiting, diarrhea, and increased risk of infection. Hair loss, in contrast to humans, is uncommon in dogs and cats on chemotherapy. In most animals, hair does not grow continually throughout their lives like it does in people. Some breeds, however, are susceptible to at least some hair loss (especially poodles, sheepdogs, Scotties and schnauzers). If your pet requires a groomer to trim its hair coat Ð then some hair loss can be anticipated. Pets, however, are not bothered much by this Ð and they seem to enjoy stylish polar-tec jackets as gifts. The good news is that the normal cell lines can almost always regenerate themselves, while the less well organized malignant cells suffer great damage. However, even at higher dosages, microscopic malignant cell clones remain alive, albeit dormant in the body. Eventually these give rise to drug-resistant cell lines. This is the biological basis of recurrent or metastatic cancers.
It is not a "given" that untoward side-effects will occur in any one patient. In fact, the majority of our patients complete their therapies without major complications. If they do occur, however, you should be prepared to recognize them and take appropriate action. Over time, the tendency is to have less frequent side effects, as the individual animalÕs sensitivity to the drug agents become known, the treatments are less frequent, and the cancer is in remission.
Risks to People Living with Chemotherapy-treated Pets
The anti-cancer drugs are excreted from the animal's body via urine and feces. This usually happens in the 48 hours following treatment, but can be as long as 5 days for Adriamycin. If it is possible, you should try to have the animal eliminate in an area away from the immediate yard or play area. Cat boxes should be changed regularly, and waste material handled with a scoop. If urine or feces must be handled, use heavy rubber or latex gloves and disposable wipes/towels. Place all waste/towels in a plastic bag and seal it, before disposal. Smooth surfaces may be washed with a dilute bleach solution (1/4 c. to 1 gallon of water). Humans and other household pets living with treated pets are generally thought not to be at any health risk, just as in the case with humans. Pregnant women should not handle ANY animal waste or anti-cancer medications. If any family member living with the pet has a condition that would suppress his/her immune system, it would be prudent to let the veterinarian know.
Gastrointestinal Side Effects
Nausea (and refusal to eat) can occur in veterinary patients, and seems to occur more frequently in cats than in dogs. If this happens 1-3 days post-treatment, it is usually transient and requires no specific treatment. Tempting the pet with favorite foods, and warming the foods slightly will often increase palatability. For dogs, adding cooked eggs, pasta, lean chicken, or hamburger can be helpful. If this condition persists, medication to reduce nausea and promote appetite can be used; metoclopramide is most commonly used in dogs; cyproheptadine for cats.
Vomiting can also occur at any time during treatment. When it occurs 1-2 days post-treatment, and the pet is otherwise bright, active, and alert you can use Pepto Bismol¬ using the label "adult dose" for dogs over 40 lbs.; "childrenÕs dose" for dogs under 40 lbs., and 1/4 tsp. for cats (dosed up to twice daily). Remove food for 12-24 hours, and replace it with a pile of ice in a dish. This will help to maintain hydration without stimulating further vomiting. If the vomiting is repetitive (greater than 4X), contains blood, or the pet seems weak and depressed, assume your pet requires immediate veterinary attention.
Diarrhea may occur, but is often mild and transient. Several over-the-counter treatments may be given safely to pets and may reduce intestinal discomfort. Imodium A-D ¬ or "Kaopectate" is dosed at "adult dose" for dogs 40 lbs. and over; "children's dose" for dogs less than 40 lbs.; and 1/4 tsp. for cats up to 2-3X daily. If the diarrhea is severe, persistent, contains blood, or the animal seems weak or depressed, veterinary attention is required.
Fever/Sepsis As previously mentioned, virtually all chemotherapeutic drugs have the ability to at least temporarily suppress the bodies own immune system. The normal range of white blood cell counts in animals is about 6,000-17,000/cmm. If the white blood cell count (neutrophils or "wbcs") are below about 2,000, then the pet runs the risk of systemic infection. The pet will usually manifest fever (but not always). If the bacteria travel through the bloodstream, it is known as "sepsis." In rare cases, shock can occur (septic shock), and without rapid treatment, the risk of death is high. Though this period of susceptibility is brief, and occurs at a fairly predictable time, its consequences can be life-threatening. Below is a list of the most commonly used drugs and the expected low point in cell counts (the "nadir"), given in days post-treatment:
High Risk Period
|Doxorubicin (Adriamycin®)||7-10 days|
|Vinblastine||5 - 7 days|
|Cyclophosphamide ( Cytoxan®)||7 - 10 days|
|Lomustine (CeeNu®)||7 days, then again at 21 days|
|Mitoxantrone||7 - 10 days|
|Cisplatin||10 - 14 days|
|Carboplatin||10 -13 days|
|Vincristine||7 - 10 days|
Signs of Fever or Sepsis
fever > 103F (temperature taken by rectal thermometer should be between 100 and 102.8 F.
extreme lethargy (refusal to get up off of dog bed, etc.)
complete disinterest in food
pale and somewhat "sticky" gums
WHAT DO YOU DO IF YOU SUSPECT INFECTION
immediate action is necessary
start the antibiotics you have been given; double the first dose, then continue as label directs
track the temperature at hourly intervals
if pet is not significantly better in 1-2 hours, call your local veterinarian or a local emergency clinic. DO NOT WAIT OVERNIGHT! This situation can be treated rapidly and almost always successfully. However, an extended delay before initiation of treatment may result in health complications or even death. Your local veterinarian has been given treatment protocols for this situation and in most cases this will be more convenient for you.
Chemotherapy treads a narrow path between effectiveness and toxicity. In fact, chemotherapeutic protocols are most often limited not by the ability of drugs to kill tumor cells, but by their toxicity to the patient. The goal is to destroy as many malignant cells as possible while leaving enough normal, "organized" cells to recover organ function. It is important, therefore, that we use the highest dosages that we think the patient can tolerate. The more cancer cells surviving any one time, the sooner the patient will become resistant to the beneficial effects of the drugs.
Visits and Costs
It is important to make an appointment for each chemotherapy administration. At each visit, a doctor or an oncology nurse will examine and treat your dog or cat. We work as a team to minimize the time you and your dog or cat will spend at the hospital. The team approach maximizes quality care and extends the time, which we are available to you. This may mean you might not see the same veterinarian or nurse each time you visit but rest assured that our intent is to provide the most comprehensive and compassionate care possible.
For a cancer such as lymphoma, therapy involves a significant time commitment on the part of the owner/family. Outpatient visits are generally once weekly for 4 weeks, then every 3 weeks for up to 18 months. Other types of cancer require less treatment time. However, we make every effort to accommodate the owner's schedule, and most visits require 20 to 30 minutes. Many clients like to leave their pet with us temporarily while they go do errands, and you are welcome to do this. You may halt therapy at any time, but we like to have the owner commit to at least 4 weeks, so you will have the benefit of seeing how well a pet can do. Due to the new OSHA hazard laws, and the fact that the animal must make no movement during the intravenous injections, we regret that it is not feasible to have the owner present during the few minutes of chemotherapy injections. Rest assured that your pet will be gently and expertly restrained by the oncology technician and the doctor. Relative to most other treatments in veterinary medicine, chemotherapy is a costly service to provide. The costs reflect the professional time and expertise required, the high costs of chemotherapy agents (the same used by humans), the special equipment and personnel protection required, and the removal of biomedical hazard waste. Realize however, that this therapy is unique in that it can successfully prolong an animal 's life!
Is It Worth It?
This is a difficult question for us to answer. Every situation and client-pet relationship is different and must be dealt with individually. If it were ever obvious that therapy was not working, or that the pet was indeed experiencing pain or discomfort, we are ethically obligated to inform you. What we can say is that most pets do indeed appear to enjoy their extended life period and do not even realize that they are "ill." However, the owner(s) must believe that they are doing the right thing for their pet and for their situation.
Prednisone is the least toxic of all the chemotherapy agents. It is not a specific chemotherapy drug, and has many different uses in medicine. It is usually well tolerated by pets. It commonly causes increased thirst, urinations, and appetite which are dose related. It can have irritating effects on the stomach lining. Please notify us if you detect a problem.
Asparaginase ( Elspar®) is also well tolerated. In rare instances, it can cause vomiting due to pancreatitis. Since it is a protein, there is a (rare) possibility that an animal can have an allergic reaction to it. We would ask that your pet remain in the lobby for about 15 minutes after this injection.
Vincristine® has little tendency to make an animal ill. Occasionally, there will be 1 or 2 episodes of "innocuous" vomiting 24 hours after the injection, which disappears without treatment. More commonly in people and cats than in dogs, Vincristine can cause intestinal cramps or constipation. The pet may seem "restless" 24-48 hours after administration. We have found that over-the-counter Imodium A-D works well in dogs ("adult dose" for dogs >40lbs; "childrens dose" if <40lbs). For cats, use any standard hairball laxative or add _ tsp of Metamucil to daily feedings. It is very irritating to the surrounding tissues if it leaks from the vein at the injection site. If you notice any inflammation where the injection was given, notify the doctor.
Cyclophosphamide (Cytoxan®) is a potent chemotherapeutic agent and can lower the white blood cell count about 7 days after it is given. Mild to moderate nausea can occur. The tablets should be given in the morning (all at once with food), and the pet should be given ample opportunity to empty his bladder throughout the day. Occasionally, bloody urine can occur due to direct bladder effects. This drug is often given with a diuretic (lasix or furosemide) to speed its excretion from the body. If your pet should get sick about 1 week post treatment, follow the instructions on the ownerÕs sheet given at the start of treatment. The caregiver should wear disposable gloves while handling the tablets.
Doxorubicin (Adriamycin®) is the most potent of the agents, and like Cytoxan®, can lower the white blood cell count and nausea and vomiting, and or diarrhea can occur. If the signs are mild, use "adult dose" Pepto Bismol for dogs >40lbs and "childrens dose" for dogs <40lbs. Moderate to severe illness requires veterinary intervention. If there is irritation at the injection sites, notify the doctor. Long-term effects can involve the heart, but our protocols have been calculated to lower this risk. If your pet gets ill about 1 week after therapy, follow the instructions on the owner's sheet.
Vinblastine (Velban®) is an injectable vinca alkaloid drug that is closely chemically related to Vincristine. They have similar effects but Vinblastine has fewer tendencies to cause intestinal side effects, though it can lower the white blood cell and platelet count.
Chlorambucil (Leukeran¨) is an oral alkylating agent which is very well tolerated. Mild decreases in appetite and white blood cell/platelet counts can occur.
Lomustine (Ceenu¨) is also an oral alkylating agent related to Cytoxan and Leukeran. While most pets tolerate this versatile drug, significant decreases in cell counts can occur and the CBC must be monitored closely.