K9 Immunity

 

Technical Info on Chemotherapy

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Canine Chemotherapy

Chemotherapy is the name given to cancer treatment using cyto-toxic chemical agents. The word cytotoxic means Toxic to Cells. This tells very well what it does. It kills cells. Unfortunately, it kills all cells, both cancer cells and healthy cells alike. The particular chemicals chosen tend to be more toxic to cancer cells than they are to normal cells, but they are still toxic to other healthy cells. As time goes on and newer chemo-therapy drugs are developed, they are getting more and more targeted towards the cancer and less deadly to healthy cells, but for now, the thing that limits the effectiveness of chemotherapy is the degree to which it is toxic to the dogs other organs.

For this reason, it is very important that the correct drug or combination of drugs be chosen for treating the specific type of cancer present. Each type of cancer is more or less responsive to different drugs. A veterinary oncologist is a doctor that specializes in the selection of the drugs used in treating the dogs cancer. It is very important that a certified veterinary oncologist be consulted when chemotherapy is considered. While it is possible for any veterinarian to administer chemotherapy drugs, this is something that cannot be recommended. Veterinary oncology is a very specialized field and oncologists receive much greater in-depth training in this area than does a general vet.

It is often stated that dogs do not have as many side effects with chemo therapy as do humans. This is both true and also misleading. The reason they do not have as many side effects is because the drugs are used in much smaller dosages, on a body-weight basis. To put it simply, smaller doses of drugs are used in dogs simply BECAUSE of the side effects. Unfortunately the smaller doses used also mean that the treatment is not as effective in dogs as it is in humans. Quite simply, chemotherapy alone does not work. It can be used advantageously along with immune supplementation, but except in very rare cases, chemotherapy does not increase either the life span or the quality of life in canine cancer patients. What it does do is it kills off the cancer cells, hopefully quicker than it kills the healthy cells. When this is combined with immunomodulation therapy that triggers the body's own response against the cancer, it can be very effective.

Below is a well written description of chemotherapy from the University of Pennsylvania:

Chemotherapy may be used as the sole treatment for certain cancers or may be used in combination with other treatment modalities, such as surgery and radiation therapy. Chemotherapy is likely to be recommended for cancer that has already spread to other areas of the body (metastatic disease), for tumors that occur at more than one site (multicentric disease), or for tumors that cannot be removed surgically (nonresectable disease). In some cases, chemotherapy can be used to try to shrink large tumors prior to surgery or to help eradicate certain types of microscopic cancer cells that cannot or have not been completely removed surgically. For cancers that are at high-risk for metastasis early in the course of disease, chemotherapy can be used after surgery or radiation therapy to help slow down the growth of cancer cells in other parts of the body.

 

Dog Cancer Types

Chemotherapy drugs attack cells in the process of growth and division. Individual drugs may work through many different mechanisms, such as damaging a cell's genetic material (DNA) or preventing the cell from dividing. However, chemotherapeutic drugs cannot distinguish between malignant cancer cells and normal cells. All rapidly dividing cells are potentially sensitive to chemotherapy. Toxicity to normal, rapidly growing or self-renewing tissues in the body is the reason for most of the side effects seen with chemotherapy. Fortunately, these normal tissues continue to grow and repair themselves, so the injury caused by chemotherapy is rarely permanent.

Compared to people who receive chemotherapy, pet animals experience fewer and less severe side effects because we use lower doses of drugs and do not combine as many drugs as in human medicine. The normal tissues that typically are most sensitive to chemotherapy are the intestinal lining, the bone marrow (which makes red and white blood cells), and hair follicles.

Toxic effects to the gastrointestinal tract are responsible for decreased appetite, vomiting, and diarrhea. These effects may be mild, moderate, or severe. In most cases, these signs are mild and usually resolve on their own or with oral medication given at home. Although infrequent, some dogs (and cats) may develop severe diarrhea requiring hospitalization and fluid therapy. In many cases, the gastrointestinal side effects from chemotherapy are not seen on the day of treatment. They often occur 3 to 5 days later.

Suppression of the bone marrow by chemotherapeutic drugs may cause a drop in the white blood cell count, leading to increased susceptibility to infection. The infection usually comes from the animal's own body (such as bacteria normally found in the intestines, mouth, skin, etc.). Severe infections may require hospitalization for intensive supportive care, including intravenous fluid and antibiotics. When a chemotherapeutic drug is used that is known to have a high potential for bone marrow suppression, a complete blood count (CBC) is checked several days after the treatment. If the white blood cell count is low but your pet is feeling well, antibiotics are prescribed as a preventive measure. Subsequent doses of chemotherapy are adjusted based on the results of the CBC. Anemia (low red blood cell count) is often a complication of cancer but is rarely caused by the chemotherapy drugs used in veterinary medicine.

Hair follicle cell in dogs (and cats) that are wire-haired or non-shedding may be particularly susceptible to chemotherapy. Certain breeds of dogs, such as terriers and poodles, will experience variable amounts of hair loss. Hair loss often is most evident on the face and tail. Whiskers and the long hairs over the eyes often fall out in cats. The hair will regrow once chemotherapy is stopped, but may initially have a modest change in color or texture.

There are many different types of chemotherapy agents and each has a different likelihood of causing side effects. If your pet is treated with drugs known to cause certain side effects, we will prescribe medications to help prevent these complications, such as antiemetics (anti-nausea and vomiting medication). In addition, we will give you instructions on what to do if and when a problem arises. We seldom see severe side effects as described above; it is estimated to be less than 5% of all pets receiving chemotherapy. With proper management, most animals recover uneventfully within a few days.

Please keep in mind that any animal can have an unexpected reaction to any medication.

How a chemotherapeutic drug is administered, how often it is given and how many treatments are given varies from case to case. The type of cancer, the extent of disease, and general health of the animal help the oncologists to formulate a treatment protocol (type of drugs, dose, and schedule used) appropriate for your pet.

Some drugs are oral medications (pills) that you give at home. Others are brief injections that require an outpatient appointment. In some instances, slow infusions or repeated treatments throughout the day may require an animal to spend the day in the hospital. The treatments are typically repeated from weekly to every third week. Blood tests may be needed to monitor the effects of chemotherapy during the weeks between drug treatments.

The duration of chemotherapy depends on the type of cancer and the extent of disease. Some animals need to receive chemotherapy for the rest of their lives. In others, treatments may be spread out or discontinued after a period of weeks to months provided that the cancer is in remission, i.e., there is no detectable evidence of cancer in the body. Chemotherapy can be resumed when the cancer relapses.

Here is a list of some of the common chemotherapy drugs used in canine cancers and what sort of side effects you can expect:


L-ASPARAGINASE:

BRAND NAMES: ELSPAR, ONCASPAR, and ERWINASE

Injectable medication only

For any medication to be effective in the treatment of cancer, some fundamental difference between healthy cells and cancer cells must exist. The chemotherapy drug must work on this cellular difference in such a way that normal cells are spared and only cancer cells are killed. L-asparaginase is an enzyme that exploits the unusually high requirement that some types of tumor cells have for the amino acid asparagine.

Asparagine is an amino acid required by all cells for the production of protein. Asparagine can be produced within a cell through an enzyme called asparagine synthetase or it can absorbed into the cell from the outside (ie it is consumed in the patient's diet, absorbed into the body and made available to the body's cells.)

Tumor cells, more specifically lymphatic tumor cells, require huge amounts of asparagines to keep up with their rapid, malignant growth. This means they use both asparagine from the diet as well as what they can make themselves (which is limited) to satisfy their large asparagines demand. L-asparaginase is an enzyme that destroys asparagine external to the cell. Normal cells are able to make all the asparagine they need internally whereas tumor cells become depleted rapidly and die.

HOW THIS MEDICATION IS USED:

This medication is used mainly against lymphoma, but can also be indicated in some mast cell tumor protocols. Unlikely other chemotherapy agents, it may be given as an intramuscular, subcutaneous, or intravenous injection without fear of tissue irritation. This is not a medication that one would use at home.

SIDE EFFECTS:

L-asparaginase is an enzyme commercially produced by bacteria. It is inherently a foreign protein and as such can produce an anaphylactic reaction. This is a rare complication but pre-treatment with anti-histamines or corticosteroids may be prudent in some cases.

L-asparaginase may interfere with blood clotting, may raise blood sugar levels, may raise liver enzyme blood tests, and may cause liver disease in some patients.

The only common side effect of this medication is vomiting.

Unlike other chemotherapy agents, suppression of blood cell production by the bone marrow is not considered to be a substantial problem with this medication.

INTERACTIONS WITH OTHER DRUGS:

Methotrexate is another common anti-tumor drug. L-asparaginase and methotrexate work against each other and should not be used together, but must be administered at least 48 hours apart.

CONCERNS AND CAUTIONS:

When L-asparaginase destroys asparagine, ammonia is a by-product. In patients with compromised liver function, the transient high levels of ammonia in the blood could pose a toxic problem. Liver disease does not preclude the use of L-asparaginase but it is important to watch for symptoms referable to liver disease (generally neurologic abnormalities/hepatic encephalopathy). The use of L-asparaginase has also been associated with pancreatitis, an inflammation of the pancrease.


CISPLATIN:

Brand Name: Platinol

Injectable Medication only

HOW THIS MEDICATION IS USED:

Cisplatin is used intravenously only. Administration is accompanied by large volumes of fluid to cause excessive urination in order to provide some measure of kidney protection. This means that your pet will have to be hospitalized on the day of treatment and should receive plenty of water and other fluids after returning home. One way to get the dog to consume lots of fluids is to offer chicken or beef broth (unsalted or lightly salted).

CANCERS FOR WHICH CISPLATIN MAY BE EFFECTIVE:

Carcinomas and osteosarcomas

SIDE EFFECTS:

Nausea beginning six hours after treatment and persisting for another six hours is expected with use of cisplatin. Anti-nausea drugs may be given to offset this.

Cisplatin can cause kidney damage. Monitoring blood tests are done regularly so that therapy can be modified should kidney enzymes become elevated.

Bone marrow suppression can occur on cisplatin. Complete Blood Cell count tests (CBC) should be regularly performed to assess the counts of different types of blood cells.

Cisplatin can be toxic to certain nerves. While this drug often causes deafness in hum ans this has not been seen in dogs. There have been several documented cases in dogs that developed nerve problems in their rear legs, effecting there ability to walk.

CONCERNS AND CAUTIONS:

Cisplatin concentrates in the liver, intestines and kidneys and is still present in the body six months after treatment but 80% eliminated in urine after 48 hours.

Cisplatin cannot be used in patients with renal disease or bone marrow suppression. Other chemotherapeutic agents must be chosen for these patients

Cisplatin impairs fertility and causes birth defects. It should not be used in breeding females unless no other options exist.


Carboplatin

Other names: Paraplatin

Very similar to Cisplatin, and useful in cancers that are unresponsive to cisplatin. Carboplatin is considerably more expensive than cisplatin and causes greater bone marrow suppression. For these reasons it is usually used only after cisplaten therapy has failed. Mainly used for Osteosarcoma and other bone cancer treatment.


Chlorambucil

Oral medicine - available in 2 mg tablets

The treatment of cancer with chemotherapy (as opposed to surgery or radiation) is especially helpful when the cancer is not localized to one body area. Using medication allows the body's blood vessels to carry the medication to even remote or otherwise inaccessible areas. In order for chemotherapy to be effective, the medications must destroy tumor cells and spare any healthy cells which may be adjacent. This is accomplished by using medications that affect cell activities that go on predominantly in cancer cells but not in normal cells. Most chemotherapy agents focus on the rapid cell division that characterizes the spread of cancer cells.

Chlorambucil is what is called an alkylating agent of the nitrogen mustard group. Alkylating agents work by binding DNA strands so that the double helix cannot unzip and replicate. (In other words, cell division is not possible). They also bind other important biochemicals impairing their function and can even break DNA strands. Cancer cells (and other cells that rapidly divide) cannot reproduce.

Alkylating agents as a group have had problems with side effects. Because Chlorambucil is relatively slow acting, fewer side effects have been an issue with this medication. The use of chlorambucil has made the treatment of numerous cancers and immune-mediated diseases more successful

HOW THIS MEDICATION IS USED:

Chemotherapy protocols for the following cancers have included chlorambucil:

Lymphocytic leukemia

Multiple myeloma

Ovarian cancer

Lymphoma

Polycythemia rubra vera

Chlorambucil is typically given daily or every other day.

SIDE EFFECTS:

The main side effect of concern with chlorambucil is bone marrow suppression. The bone marrow is one's source of all blood cells - both white cells and red cells. When the bone marrow is suppressed, one can develop an anemia (inadequate amount of red blood cells), a drop in white cells (which constitute the bulk of the immune system), or both. This side effect is generally evident at some point during the second week of therapy and blood testing at this time is definitely in order to determine if this side effect is occurring. Once the medication is discontinued, the marrow should recover in another 1-2 weeks, though more severe and long lasting suppression has rarely occurred. Immune Modulating compounds tend to offset this negative side effect.

Poodles and Kerry Blue Terriers may have hair loss problems on chlorambucil but the hair loss humans experience with chemotherapy generally does not occur with dogs.

Overdose of chlorambucil results in bone marrow suppression in all cell lines as well as seizuring.

INTERACTIONS WITH OTHER DRUGS:

Chlorambucil's bone marrow suppression side effect may be compounded if chlorambucil is used with other medications that also share possible bone marrow suppression as a side effect. Such medications include:

Chloramphenicol

Azathioprine

Colchicine

Cyclophosphamide

The use of chlorambucil may lead to the need to increase the dose of allopurinol for patients who take it (such as uric acid bladder stone forming Dalmatians).

CONCERNS AND CAUTIONS:

The DNA poisoning effects of this medication precludes its use in pregnant patients; further, pregnant women should not handle this medication, nor the urine/feces of animals taking chlorambucil.

Chlorambucil should not be used in patients with pre-existing bone marrow suppression.

Chlorambucil is suppressive to the immune system and should be used with caution in patients already immune suppressed or with chronic infections.

Immune Modulating compounds are highly recommended for concomitant use with chlorambucil to help offset these immune suppression effects.

Chlorambucil may cause permanent infertility when given to patients prior to puberty.

Some authorities list such drugs as Benadryl and Prednisone as chemotherapy agents, but we opt to exclude these here since they do not fit the definition of cytotoxic chemicals used in the treatment of cancer.

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NOTE: The information and statements contained on this on this website have not been evaluated by the Food and Drug Administration and is provided for informational purposes only. It is not meant to substitute for the advice provided by your veterinarian. Our products are not intended to diagnose, treat, cure or prevent any disease. Health decisions for your pet are much too important to be made without the advice of a veterinarian. We invite and encourage you to share this information with your veterinarian.