Even though the oncologist carefully plans your pet's protocol, hoping to kill the tumor cells and avoid harming the patient, there are always some adverse effects on normal body tissues (fig.1).
Figure 1: Unfortunately, normal cells can also be affected by chemotherapy.
Chemotherapeutic drugs are targeted to kill tumor cells, which generally divide more rapidly than normal cells. However, cells in certain tissues in the body also divide rapidly, and these may be injured by the drugs as well. Blood cells (made in the bone marrow), cells in the reproductive tract (sperm cells and dividing ovarian follicles), cells of the hair follicles, and gastrointestinal cells all divide rapidly, and therefore can be expected to sustain some damage during chemotherapy treatment. Other drugs may cause specific damage to particular organs, such as the heart, liver, or kidneys. Side effects differ for each chemotherapy drug and may be different for each individual animal treated; for example, some animals seem to be more predisposed to gastrointestinal side effects than others, and may experience nausea or vomiting when the great majority of other animals tolerate the drug very well.
When bone marrow suppression is caused by chemotherapy, the white blood cells, red blood cells, and platelets may be suppressed (fig.2).
Figure 2: Suppression of the normal bone marrow by chemotherapy can result in anemia, neutropenia, and thrombocytopenia. 
White blood cells (neutrophils) help to protect against bacterial invasion, and a very low count (neutropenia) may predispose a patient to an infection such as pneumonia. Platelets are tiny cells that assist in the formation of a blood clot. The patient with a low platelet count (thrombocytopenia) may have hemorrhagic tendencies, with such occurrences as nosebleeds or bleeding from the gums. Black, tarry stools may also be noted, caused by bleeding into the stomach and intestine. Chemotherapeutic damage to red blood cell formation in the bone marrow or loss of blood by hemorrhage may lead to anemia, a condition in which the patient is pale and cannot adequately oxygenate tissues, with resultant fatigue and intolerance of normal exercise. Damage to the blood cell-producing tissues of the bone marrow, or myelosuppression, is very common with chemotherapy; almost all patients experience this at one time or another during treatment. The lowest count your dog or cat will have during treatment is called the nadir, which is usually seen at a different time after therapy for each drug administered. Your oncologist will take blood samples from your pet at periodic intervals to check to see whether his cell counts are at safe levels, and to tell whether the next drug can be administered. You should know the signs that might suggest that your pet's blood cell counts are too low, so that you can seek immediate attention from your veterinarian. These would include fever, coughing, loss of appetite for more than a day or so, vomiting/diarrhea, small hemorrhages on the gums or over the skin of the abdomen, or urinating more frequently with only small amounts of urine produced each time. You should purchase a thermometer for your pet, and learn how to take his temperature rectally. The normal temperature for a dog or cat is 100-102° Fahrenheit. Always take your pet's temperature when he has been resting indoors for a while, since playing outside or other exercise may elevate his temperature. You should call your veterinarian if your dog or cat's temperature rises to 103.5° Fahrenheit or more, since this may be a sign that neutrophil numbers are dangerously low. Your doctor will probably prescribe antibiotics, and may hospitalize your pet if he is severely ill. Sometimes prophylactic antibiotics to prevent infection will be prescribed if the animal's neutrophil count is low, even if there is no evidence of infection at the time. Certainly, if your pet seems ill or has a fever while receiving chemotherapy, do not give any more chemotherapy drugs until your veterinarian has said that it is safe to do so!
A patient receiving chemotherapy may have loss of appetite (anorexia) for a few days or for a long time. Since advanced cancer may cause anorexia even without treatment, it is sometimes difficult to tell whether the appetite decrease is caused by the cancer or by the anticancer drugs that are being administered. If the drugs are causing the problem, the patient's appetite should return after the drugs are discontinued. In some animals, loss of appetite related to treatment with a particular drug may be serious enough that it may cause the oncologist to recommend discontinuing administration of that drug permanently. Cats seem to lose their appetite with chemotherapy much more frequently than dogs do. Humans report alterations in their sense of smell and in the taste of foods after receiving chemotherapy, such that a favorite food may suddenly taste or smell bad. Cats are exquisitely sensitive to changes in the taste and smell of their food, and any change may cause them to avoid that food permanently. It may be this effect of chemotherapy on smell and taste that causes cats to become anorexic more frequently than dogs. A few weeks after chemotherapy has ended, taste and smell sensations should return to normal, however.
Because of the effects of chemotherapy on the rapidly dividing cells of the gastrointestinal tract, chemotherapeutic drugs may cause nausea, vomiting, and/or diarrhea. Signs that your pet is nauseated would be loss of appetite, excessive salivation, frequent swallowing, and retching. Although there are new medications to both prevent and treat the nausea and vomiting of chemotherapy, these are expensive and not generally used to prevent nausea caused by cancer treatment in animals at this time (fig.3)
Figure 3: Newer medications are available in both injectable and oral forms to treat nausea and vomiting.
. A day or two of nausea or a vomiting episode or two during chemotherapy is not unexpected and is rarely dangerous. If your animal does not eat or drink for one day or longer, if he begins to vomit and cannot hold water down, or if you notice blood in the vomitus or in the diarrhea, you should inform your veterinarian immediately, since your pet may become dangerously dehydrated. Occasionally, intravenous fluids are necessary to support the patient through the episode.
In some dogs and cats, thinning of hair or hair loss may occur just as it does in people. In man, hair loss occurs because the hairs are continually growing. In most dogs and cats, the hairs grow and shed in a cycle and are not growing in a continuous fashion.
Figure 4: A poodle before chemotherapy treatment.
Thus, most pets will not lose their hair during chemotherapy treatment. Poodles, poodle-type mixed-breed dogs, and certain breeds of terriers have hair that is continuously growing, however, and these pets will experience the same sort of hair loss that is seen in humans (fig.4-5). Most cats will lose their whiskers during chemotherapy, but their hair coat will usually remain normal in appearance (fig.6). Hair loss during chemotherapy is temporary and regrowth begins after chemotherapy ceases. The dog or cat usually does not seem to care that he has no hair, but it is important that owners deciding on chemotherapy for their pet consider the
Figure 5: A poodle that developed hair loss following chemotherapy treatment.possibility that hair loss may occur.
In show dogs and cats that are to be used for breeding, 
owners must take into account the fact that chemotherapy may cause temporary or permanent damage to reproductive tissues (fig.7). Sperm counts may drop so that the male dog or cat is infertile, and the female animal may cease cycling or fail to ovulate, at least for a while. Which, if any, reproductive problems develop depends on the age of the individual being treated, the
Figure 6: Cats often loss their whiskers after receiving chemotherapy. dose and duration of the chemotherapy, and the chemotherapy drug(s) that are being given. In male dogs, owners who had planned to bree
d their pet in the future may consider storing sperm in a canine semen bank. The American Kennel Club (AKC, 5580 Centerview Drive, Raleigh, NC 27606-3390, Telephone # (919) 233-9767) can provide a list of those individuals/companies involved in collecting/storing canine semen with record-keeping methods that have been deemed by AKC to be in compliance with its regulations. While it is possible for a female dog or cat to conceive
Figure 7: Sperm abnormalities and infertility are common side effects of chemotherapy in the breeding animal.
during chemotherapy treatment, the toxicity of many of the drugs may cause birth defects in the offspring. Therefore, it is suggested that non-neutered female dogs receiving chemotherapy be confined when they are in heat.
Certain chemotherapy drugs can damage the muscle of the heart, sometimes leading to heart failure; this is rare in the cat, but occurs with some frequency in the dog. The most common cardiotoxic drug used in veterinary oncology is doxorubicin (Adriamycin®) (fig.8).Generally, the heart failure associated with doxorubicin is dose-related. It is an accumulative toxicity---that is, it does not generally occur until a certain accumulative dosage has been
Figure 8: The dose limiting toxicity of doxorubicin in man and dogs is cardiotoxicity.
reached, generally not before 6-8 treatments. However, abnormal heart beats (arrhythmias) have been reported in some dogs after just one doxorubicin treatment. Dogs with pre-existing heart problems are at much higher risk for earlier signs of heart damage from the drug. If a veterinarian suspects heart disease (clinical signs of an unexplained cough, abnormal heart beats or a heart murmur heard when listening to the heart), an assessment of the patient's heart function will probably be done before chemotherapy is started to assure that there are no major problems. During the time of the treatments, the dog's heart function may also be checked periodically to assure that no changes have occurred. One of the cardiac tests that may be performed is echocardiography, which evaluates the contractility and function of the heart. An electrocardiogram (ECG) may also be needed to check for abnormal heart beats. Certain breeds of dogs are predisposed to the development of cardiomyopathy (heart muscle disease) as they grow older, and doxorubicin may be dangerous for these patients. Boxers, Doberman Pinschers, and several other large and giant breeds are known to have cardiomyopathy as breed-related problems, and the veterinary oncologist may be especially cautious in these dogs.
Many of the breakdown products of chemotherapy drugs are eliminated from the body through the kidneys. Certain drugs and drug byproducts can damage the kidneys or bladder. These drugs cannot be used safely in dogs or cats with a previous history of kidney damage. Even in dogs with normal kidney function, frequent laboratory checks of kidney function will be necessary as these drugs are given. Two drugs currently used in chemotherapeutic protocols in animals, cyclophosphamide (Cytoxan®) and ifosfamide (Ifex®), can cause hemorrhagic cystitis (blood in the urine due to inflammation of the bladder wall) (fig.9)
Figure 9: A unique toxicity of cyclophosphamide is the development of hemorrhagic cystitis. 
. This side-effect can continue for some time even after the drug is stopped, and the dog's straining to urinate small volumes of bloody urine may produce a great deal of concern for the owner. If chemotherapy with one of these drugs is continued after signs of hemorrhagic cystitis begin, the inflammation and irritation of the bladder wall may become a serious or permanent problem. For this reason, a veterinary oncologist will always want to check a urine sample from your pet prior to beginning chemotherapy, to look for the presence of blood (or infection). Also, urinalyses will probably be performed periodically during the treatment to make sure that a problem is not beginning. If your animal is receiving chemotherapy and you notice any blood in your dog's urine, see your doctor immediately for evaluation of the problem.
