Chemotherapy Drugs

The following information is simply informational. It’s intent is not to replace the advice of a veterinarian nor to assist you in making a diagnosis of your pet. Please consult with your own veterinary physician for confirmation of any diagnosis. Your pets life may depend on it.

This is not an all-inclusive list. Though it mainly consists of Chemotherapeutic drugs, other drugs which are widely used in cancer dogs are also included below. We will be adding more information on chemotherapy drugs as it becomes available to us. Unless otherwise stated, the following work was originally published by Veterinary Information Network, Inc. (VIN) and is republished with VIN’s permission.


(Brand names: ELSPAR, ONCASPAR, ERWINASE) Available as injectable only.


To make an effective medication for the treatment of cancer, some fundamental difference between normal cells and cancer cells must be defined. The chemotherapy agent must exploit this cellular difference such that normal cells are spared and only cancer cells are injured. L-asparaginase exploits the unusually high requirement tumor cells have for the amino acid “asparagine.”

Asparagine is an amino acid required by 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.


Mostly this medication is used against lymphoma but it also is used 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.


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.


Methotrexate is another common anti-tumor drug. L-asparaginase and methotrexate work against eachother and should be administered at least 48 hours apart.


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 been associated with pancreatitis.




Prednisone and prednisolone are members of the glucocorticoid class of hormones. This means they are steroids but, unlike the anabolic steroids that we hear about regarding sports medicine, these are “catabolic” steroids. Instead of building the body up, they are designed to break down stored resources (fats, sugars and proteins) so that they may be used as fuels in times of stress. Cortisone would be an example of a related hormone with which most people are familiar. Glucocorticoids hormones are produced naturally by the adrenal glands.

We do not use the glucocorticoids for their influences on glucose and protein metabolism; we use them because they are also the most broadly anti-inflammatory medications that we have. Their uses fit into several groups:

  1. Anti-inflammatory (especially for joint pain and itchy skin)
  2. Immune-suppression (treatment of conditions where the immune system is destructively hyperactive. Higher doses are required to actually suppress the immune system)
  3. Cancer Chemotherapy (especially in the treatment of lymphoma)
  4. Central Nervous System Disorders (usually after trauma or after a disc episode to relieve swelling in the brain or spinal cord)
  5. Shock (steroids seem to help improve circulation)
  6. Blood Calcium Reduction (in medical conditions where blood calcium is dangerously high treatment is needed to reduce levels to normal)

Prednisone is activated by the patient’s liver into Prednisolone.

Prednisolone may be administered in tablet form or produced by the body from prednisone. These medications are considered to be interchangeable.


Prednisone & prednsolone have activity in the kidney leading to the conservation of salt. This creates the classical side effects of prednisone/prednisolone use: excessive thirst and excessive urination. If this occurs, another steroid can be selected or the predisone/prednisolone dose can be dropped.

Prednisone/prednisolone are commonly used for several weeks or even months at a time to get a chronic process under control. It is important that the dose be tapered to an every other day schedule once the condition is controlled. The reason for this is that body will perceive these hormones and not produce any of its own. In time, the adrenal glands will atrophy so that when the medication is discontinued, the patient will be unable to respond to any stressful situation. An actual circulatory crisis can result. By using the medication every other day, this allows the body’s own adrenal glands to remain active.

Any latent infections can be unmasked by prednisone use. (Feline upper respiratory infections would be a classical example. When a cat recovers clinically, the infection simply goes dormant. Glucocorticoid use could bring the infection out again.)

Glucocorticoid hormone use can be irritating to the stomach at higher doses.


Glucocorticoid hormones should not be used in combination with medications of the NSAID class (ie aspirin, Rimadyl, phenylbutazone etc.) as the combination of these medications could lead to bleeding in the stomach or intestine. Ulceration could occur.


Prednisone and prednisolone are considered to be intermediate acting steroids, meaning that a dose lasts about a day or a day and a half. After two weeks or more of use, it is important to taper the dose to an every other day schedule so as to keep the body’s own cortisone sources able and healthy.

The same salt retention that accounts for the excessive thirst and urination may also be a problem for heart failure patients or other patients who require sodium restriction.

Diabetic patients should never take this medication unless there is a life-threatening reason why they must.

Glucocorticoid hormones can cause abortion in pregnant patients. They should not be used in pregnancy.

Prednisone/Prednisolone use is likely to change liver enzyme blood testing and interfere with testing for thyroid diseases.

When prednisone/prednisolone is used routinely, serious side effects would not be expected. When doses become immune-suppressive (higher doses) or use becomes “chronic” (longer than 4 months at an every other day schedule), the side effects and concerns associated become different. In these cases, monitoring tests may be recommended or, if possible, another therapy may be selected.


(Also called cis-Platinum II, cis-DDP, CDDP, DDP, or cis-diamminedichloroplatinum)


Cancer is the condition where a significant number of malignant cells have defeated the body’s natural protective mechanisms and have proliferated.

Malignant cells are dangerous because they have reverted to characteristics typical of embryonic cells. Instead of doing the jobs that normal cells of their tissue type are supposed to do, they simply divide rapidly over and over and ultimately obliterate the normal tissue from whence they came. Often they invade local lymphatic or blood vessels so as to spread to distant body areas and set up new cancerous areas far from where they originally started.

If a group of cancer cells is localized to one area it may be possible to surgically removed them but treatment is more difficult if they have spread. For this situation, we need medications that selectively kill cancer cells and leave normal cells alone. We can use the body’s own bloodstream to carry these medications to all the distant sites where cancer may have set up. . This kind of treatment is called “chemotherapy.”

Most chemotherapy drugs target the fact that cancer cells are rapidly dividing and interfere with cell division. I is not known exactly how cisplatin attacks cancer cells.


Cisplatin is used intravenously only. Administration requires a process called “diuresis,” which helps protect the patient’s kidneys from damage. This means that your pet will have to be hospitalized on the day of treatment and receive intravenous fluids.

Tumors for which cisplatin is effective:

Tumors for which cisplatin is effective:

  1. Squamous cell carcinoma
  2. Transitional cell carcinoma
  3. Ovarian carcinoma
  4. Mediastinal carcinoma
  5. Osteosarcoma
  6. Nasal carcinoma
  7. Thyroid carcinoma


Nausea beginning six hours after treatment and persisting for another six hours is expected with use of cisplatin.

Cisplatin can cause kidney damage. Monitoring blood tests are done regularly so that therapy can be modified should kidney parameters elevate.

Bone marrow suppression can also occur on cisplatin. Monitoring tests are also regularly performed to assess the counts of different blood cells.

Cisplatin can interfere with normal hearing by affecting the cochleovestibular nerve which controls hearing. (Cisplatin is what is called an “ototoxic” drug.) In humans, a cisplatin-associated neuropathy has been described (involving a sensory nerve interference). This has not been documented in the dog but several cases of dogs who developed nerve problems (“Lower Motor Neuron” weakness) in their rear legs have been reported. It is not clear if this weakness, though, was part of their cancer syndrome or due to the medication.


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.

Cats are vulnerable to severe pulmonary (lung) side effects and cannot receive cisplatin.

Cisplatin cannot be used in patients with renal disease or bone marrow suppression. Patients with renal disease can take another medication called Carboplatin.

Cisplatin impairs fertility and causes birth defects.





The treatment of cancer with medication (as opposed to surgery or radiation) is especially helpful when the cancer in question 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. This form of treatment is called “chemotherapy.”

In order for chemotherapy to be effective, the medications must destroy tumor cells and spare the normal body cells which may be adjacent. This is accomplished by using medications that affect cell activities that go on predominant 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. Lymphocytes, whose normal function involves antibody production and other immune activities, are also very sensitive to the effects of alklyating agents thus making the alkylating agents helpful in treating immune-mediated diseases (i.e. disease where the immune system erroneously attacks the body).

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, especially in feline use. The use of chlorambucil has made the treatment of numerous cancers and immune-mediated diseases more successful especially in cats.


Chemotherapy protocols for the following cancers have included chlorambucil:

  1. Lymphocytic leukemia
  2. Multiple myeloma
  3. Ovarian cancer
  4. Lymphoma
  5. Polycythemia rubra vera

Immune Mediated conditions where chlorambucil may be especially helpful include:

  1. The Pemphigus diseases
  2. Eosinophilic Granuloma Complex
  3. Inflammatory Bowel Disease
  4. Feline Infectious Peritonitis
  5. Immune-mediated hemolytic anemia
  6. Immune-mediated platelet destruction

Chlorambucil is typically given daily or every other day.


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.

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 and cats.

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


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:

  1. Chloramphenicol
  2. Azathioprine
  3. Colchicine
  4. 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).


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 (such as FIV+ cats) or with chronic infections.

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



(Oral suspension is too high in alcohol content to be used for animals)


Histamine is an inflammatory biochemical that causes skin redness, swelling, pain, increased heart rate, and blood pressure drop when it binds to one of many “H1″ receptors throughout the body. Histamine is a very important mediator of allergy in humans, hence a spectacular array of different antihistamines has proliferated. Histamine, perhaps unfortunately, is not as important a mediator of inflammation in pets which means results of antihistamine therapy are not as reliable in pets.


Diphenhydramine has several important effects and thus several uses. Most obviously, diphenhydramine is an antihistamine and it is used for acute inflammatory and allergic conditions such as:

  1. Snake Bites
  2. Vaccination reactions
  3. Blood transfusion reactions
  4. Bee stings and insect bites

Diphenhydramine is frequently included in antihistamine trials for allergic skin disease. It is not one of the more effective antihistamines in this regard but its availability and inexpensiveness make it worth trying in many cases.

Mast cell tumors are tumors involving cells which contain granules of histamine. Patients with mast cell tumors experience chronic inflammatory symptoms due to circulating histamine. Antihistamines such as diphenhydramine may be helpful given long term.

Diphenhydramine has a strong anti-nauseal side effect which makes it helpful in treating motion sickness.

Diphenhydramine causes drowsiness in animals just as it does in people and can be used as a mild tranquilizer.


With so many possible uses of this medication, it is difficult to separate out a side effect from a primary effect. Drowsiness is generally regarded as an undesirable side effect.

At doses higher than the recommended dose, human patients complain of dry mouth and experience difficulty with urination.


In the treatment of allergic skin disease, antihistamines are felt to synergize with omega 3 fatty acid supplements and, as a general rule for this condition, it is best to use these medications together.

Diphenhydramine should not be used with additional tranquilizing medications.

In animals that experience a hyperactivity reaction while taking Metoclopramide (Reglan), this effect can be reversed with a dose of Diphenhydramine.


It is important to realize that the name “Benadryl” is a brand name. It is easy to try to save money and try to buy over-the-counter diphenhydramine and end up with an inappropriate product. It would seem like it would contain diphenhydramine but, in fact, it contains a combination of diphenhydramine and other medications, including a dose of acetaminophen which could be lethal to a pet.

Never buy over-the-counter medication for your pet without knowing exactly what you are supposed to get and never medicate your pet without your vet’s guidance.


AVAILABLE IN 15 mg (1/4 GRAIN), 30 mg (1/2 GRAIN), & 60 mg (1 GRAIN) TABLETS


When animals have frequent seizures, medication becomes necessary. In the dog and cat, phenobarbital is probably the first choice for seizure suppression. It is effective, safe if used responsibly, and is one of the least expensive medications in all of veterinary practice. Since treatment with phenobarbital is generally life-long, monitoring blood tests are periodically recommended.

Most often phenobarbital is used to suppress epileptic seizures (i.e., seizures for which a cause has not been identified) but phenobarbital can also be used against seizures due to brain tumors, poisonings, or infection as well.

Phenobarbital is absorbed well into the body when given orally and it’s peak activity occurs 4-8 hours after the pill is given.

When phenobarbital is started, it takes 2-4 weeks to reach a stable blood level and cannot be fully relied upon to prevent seizures until this period has elapsed. It is usual to run a blood phenobarbital level at the end of this period to determine how the pet is absorbing the medication.


Excessive thirst and urination and excessive appetite are not uncommon side effects of phenobarbital. If they occur, they do not generally go away as the patient adjusts to medication. If they are severe, medication may have to be changed.

It is not unusual for some patients to demonstrate depression or sedation when phenobarbital therapy is initiated. This effect is generally transient and resolves as the patient acclimates to the medication. If this problem has not resolved after two weeks, a phenobarbital blood level can be drawn to determine if the dose is too high for the individual in question. Running a blood level sooner may not be useful as it takes a couple of weeks to achieve a stable and meaningful blood level.

Rarely, anemia (lack of red blood cells) can occur with phenobarbital exposure. Should this occur, a different seizure medication should be selected.

Chronic exposure to phenobarbital can lead to scaring in the liver and liver failure that can be irreversible. Proper monitoring tests are geared for heading off such an event in plenty of time to change medication.


Phenobarbital is able to “induce” the metabolic enzymes, thus making them more efficient at removing toxins. Part of this phenomenon involves elevation of liver enzyme tests on a blood panel. As previously mentioned, monitoring by periodic blood testing is important in catching any impending liver problems while they are still insignificant but this is complicated because elevations in liver enzymes occur with normal phenobarbital usage.

There are many monitoring protocols. Our hospital recommends a phenobarbital blood level drawn at the time of day when the level is the lowest (a “trough” level) 3-4 weeks after starting phenobarbital followed by a similar phenobarbital level every 6 months. We also run a liver function test called a “bile acids” test every 6months to accompany the phenobarbital level.


Phenobarbital is removed from the body primarily by the liver (75% is removed by the liver, 25% by the kidney). As mentioned, in the liver, phenobarbital has a unique ability to “induce” the microsomal enzymes which means in more simple terms that chronic exposure to phenobarbital makes the liver more efficient at removing other toxins. Other medications which will not work as well in the presence of phenobarbital include: lysodren (treatment for Cushing’s disease), chloramphenicol (an antibiotic), corticosteroids (such as prednisone, desamethasone), doxycycline (an antibiotic), cardiac beta-blockers, quinidine (a heart rhythm medicine), theophylline (an airway dilator), and metronidazole (a multi-purpose antibiotic/GI medicine). They will not work as well because they are removed from the body much faster than usual by the phenobarbital induced enzymes.

Phenobarbital’s activity can be enhanced by concurrent administration of the following medications: chloramphenicol (an antibiotic), any anti-histamine associated with drowsiness, or any other sedative or tranquilizer.Rifampin, a special antibiotic, may reduce the effectiveness of phenobarbital when the two are used concurrently.If phenobarbital is used with griseofulvin (treatment for ringworm), the griseofulvin may not be absorbed optimally into the body and may not be as effective.When unacceptable side effects develop with phenobarbital use, phenobarbital dose may be substantially cut back or even discontinued. Potassium bromide can be used as a seizure control medication in such cases.Primidone is another anti-seizure medication that was once more popular in the past. The liver converts primidone to phenobarbital thus it is generally more efficient (and less expensive) to simply use phenobarbital. Further, if there is any question about liver function in a seizure patient, phenobarbital is likely to be a better choice.


Missing even one phenobarbital dose can be enough to trigger a seizure.

It is very important to comply fully with medication recommendations.Because of the induction of microsomal enzymes previously mentioned, it is normal to see elevated liver enzymes (“AST”, “ALP”, and “ALT”) on any blood chemistry that is performed. This makes interpretation of these values somewhat difficult.
The blood level of phenobarbital attained in an individual is not completely predictable by knowing the oral dose given. With time, the patient’s liver becomes especially able to remove phenobarbital from the system and the level may go down. Or the opposite may be true and the liver becomes less efficient so that blood level goes up. For these reasons, blood levels of phenobarbital are periodically measured so as to periodically adjust the oral dose as noted above.In patients with poor liver function or liver failure, phenobarbital may not be the best choice in seizure control.The use of phenobarbital will interfere with thyroid function testing as well as with adrenal function testing. Monitoring hypothyroidism or Cushing’s disease in patients taking phenobarbital is extremely difficult as test results will be difficult to interpret.


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.

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.

We usually recommend that every patient receive at least 2 cycles of chemotherapy and then be evaluated for response before we decide to continue the treatment, change drugs or discontinue chemotherapy.It is imperative that you, as a pet owner, are committed to treatment and that you bring your pet to the veterinary hospital when scheduled for therapy. In many cases, we are unable to cure our veterinary cancer patients.

Our goal is therefore to improve a pet’s quality of life. To this end, chemotherapy can be used to minimize the discomfort caused by a tumor or to slow down the progression of the disease. For most (but not all) types of tumors, the oncologist will provide information on average life expectancy with and without treatments.The decision of whether to pursue chemotherapy treatments can be complex.

Medical information, practical concerns (such as need for repeated visits, your pet’s temperament, etc.), and financial responsibility all play a part in this decision. We encourage you to discuss your concerns with the oncologist and/or our social worker when making this decision.