The Dog Cancer Survival Guide (122 page)

A group of drugs, called antimetabolites, can be useful in treating cancer because of their ability to masquerade as part of the cancer cell. These plant alkaloids mimic the building blocks of DNA; when the cancer cell uses them to build new DNA, its structure is permanently weakened and the cell dies.

One of the most popular of the antimetabolites is cytosine arabinoside. Used in leukemia and some lymphoma protocols, it interferes with the ability of the cancer cell to repair DNA or replicate. Cytosine arabinoside can cross the blood-brain barrier, which means that it can enter the nervous tissue in the brain and spinal cord. This makes it useful for lymphomas that are “hiding” in those tissues.

Cytosine arabinoside attacks cancer during the replication phase of the cell cycle (the S-phase or synthesis phase), only. To make sure the drug kills as many cancer cells as possible, it is dripped from an IV continuously over a long period of time, sometimes twelve or even twenty-four hours. Your dog is in the hospital during the entire course of treatment. Some oncologists avoid hospitalizing dogs, by dividing the dose into two to four fractions, which are given by subcutaneous injection over two days.

Some vomiting and diarrhea occur with cytosine arabinoside, and the main side effect is bone marrow suppression, which must be monitored with follow up CBCs.

Another antimetabolite is methotrexate, which is used in some lymphoma protocols. Methotrexate works by blocking folic acid, an important nutrient, needed to build new cancer cell DNA. The most common side effects are gastrointestinal; it may cause severe nausea, vomiting and diarrhea.

Methotrexate can also cause low red blood cell counts (anemia) and, with high doses, liver toxicity and kidney damage.

The antitumor metabolites are another class of drugs, which include a type called anthracyclines. Anthracyclines work in several phases of the cell cycle, to cross-link DNA strands and alter the function of the enzyme topoisomerase type II, which winds and unwinds DNA during replication. Some anthracyclines, such as doxorubicin, can also produce free radicals, which damage DNA and the cell’s membrane.

Doxorubicin (brand name Adriamycin) is an extremely powerful chemotherapy drug that is used in many protocols. Used alone or in combination with other drugs, it’s the basis of protocols for lymphoma, osteosarcoma, hemangiosarcoma, mammary cancer and a wide variety of carcinomas.

One of the ways doxorubicin kills cancer cells is by generating free radicals. Those free radicals create oxidation, which harms cancer cells, so you do not want to counteract that oxidation with mega-doses of antioxidants. As Dr. Dressler has discussed throughout this book, antioxidants sometimes interfere with chemotherapy drugs, and doxorubicin is the classic example of this phenomenon. If your dog is on doxorubicin, do not give antioxidants or substances that act like antioxidants; stop them one week before and one week after doxorubicin.

Doxorubicin is a fluid, administered by IV, directly into a vein through an indwelling catheter. Like Mustargen, it is a potent vesicant and causes severe damage to skin and other tissues. These injuries, in some severe cases, can require surgery to repair, and the tissue is typically slow to heal. For this reason, the drug must be directly injected into a vein and always through an indwelling IV catheter that is carefully placed for proper and safe administration.

Doxorubicin can cause expected side effects, such as hair loss, nausea, vomiting, diarrhea and bone marrow suppression (all discussed in
Chapter 11
). It can also cause an acute (sudden) allergic reaction in the body called anaphylaxis. During anaphylaxis, the immune system reacts to the drug by releasing histamines (the same thing can happen to people or dogs with “allergies,” when an environmental allergen like pollen is encountered).

Rarely, anaphylaxis occurs during administration. Symptoms include vomiting, red skin, itchiness and difficulty breathing. Anaphylaxis can be treated with antihistamines, like diphenhydramine (brand name Benadryl) or corticosteroids. Symptoms usually reverse in the treatment room, and do not recur at home.

To avoid anaphylaxis, I recommend giving antihistamines before administering doxorubicin. Slow administration of the drug over twenty to thirty minutes also helps lower the chances that your dog will have an allergic reaction. In addition, I use Adriamycin, rather than the generic form of doxorubicin, because published data show that it causes less anaphylaxis. In one study, thirty-four dogs were given both Adriamycin and the generic form. While Adriamycin caused zero side effects, the generic form caused itchiness, head-shaking, red skin, vocalization, vomiting, and high heart and breathing rates in thirteen out of the thirty-four afflicted dogs (44%). If you are going to use this potent drug, I strongly recommend using Adriamycin rather than the generic.

There is a risk for heart problems on doxorubicin. In the short term, abnormal heart rhythms (arrhythmias) can develop. These usually only occur during the actual administration of the drug, and cease when the treatment is over. The slow administration I recommend helps to reduce the likelihood of arrhythmias.

Chronic heart problems can also develop from using multiple doses of doxorubicin (more than six to eight doses) and sometimes these are long term, showing up months or years after treatments have ended. For example, dilated cardiomyopathy (DCM) can occur, a serious condition in which the heart grows enlarged and weakened and cannot pump blood effectively. As the body gets less blood supply, heart failure can occur or shortness of breath, coughing, swelling and lethargy can be experienced. Obviously, the quality of life can really plummet as a result of this condition.

DCM and other heart problems rarely occur as a result of just one dose of doxorubicin, and they are usually not seen, if the doses are limited. For this reason, I recommend no more than six to eight doses of doxorubicin. I also check for pre-existing heart problems before using doxorubicin, and weigh the decision carefully, when such a history exists. I also take extra care with deep-chested or giant breeds, because some are predisposed to heart disease (Dobermans and Boxers, for example).

Some oncologists recommend administering dexrazoxane (an iron chelator) just before administering doxorubicin because it can reduce the risk of heart toxicity. This combination is generally well tolerated, with minimal side effects, so I use this drug, also, when I suspect heart toxicity might be a problem. However, I decide on a case-by-case basis, because it is not yet known whether dexrazoxane’s antioxidant properties interfere with doxorubicin’s efficacy.

To protect your dog from infection, due to possible bone marrow suppression, I consider the use of preventative antibiotics. A recent study revealed that dogs with lymphoma and osteosarcoma, who received preventative antibiotics to help with bone marrow suppression, had lower hospitalization rates, lower toxicity and performed better overall.

Doxorubicin is more likely than some other chemotherapy drugs to affect appetite and/or cause nausea, vomiting or diarrhea. For this reason, I routinely recommend preventative oral medications (maropitant, brand name Cerenia) for the four days after treatment. This decision is validated by a recent placebocontrolled study in which dogs on the placebo experienced more and more severe vomiting and diarrhea than the dogs on Cerenia.

Doxorubicin is a powerful chemotherapy agent, and it’s used in quite a few protocols because it can be very effective. The decision to use it is a complicated one, and must be considered carefully and in deep consultation with your vet or oncologist.

Also, keep in mind that it is broken down in the liver and excreted in the feces – so take extra care when you clean up after your dog (as outlined on
page 134
).

Mitoxantrone is another anthracycline. It’s used alone or in combination protocols to treat lymphoma, some sarcomas and some carcinomas, including anal sac adenocarcinoma and transitional cell carcinoma (TCC). Mitoxantrone is not as effective for lymphomas as doxorubicin; however, it is sometimes used as a replacement because it is not as toxic to the heart. For other cancers, like TCC, it is the drug of choice.

The most common side effect of mitoxantrone is bone marrow suppression. It usually lowers white blood cell counts, sometimes to severe levels. Other expected side effects, like nausea, vomiting and diarrhea, are typically mild.

Because it does not form free radicals, it is all right to use antioxidants with mitoxantrone.

Mitoxantrone is an irritant and must be injected directly into a vein. If it does contact other tissues, however, it is not as damaging as Mustargen and doxorubicin, and the damage can usually be treated topically.

Mitoxantrone is a distinctive blue liquid, so you may see a bluish hue to your dog’s urine, or you may see the whites of his eyes turn a light shade of blue. This is normal and not considered toxic.

There is a type of chemotherapy drug that uses enzymes to battle cancer. One that I use in dogs with cancer is L-asparaginase (also called Elspar).

Instead of directly killing cancer cells, L-asparaginase breaks down asparagine, an amino acid and a building block for proteins. When asparagine breaks down, the cancer cell cannot create the necessary proteins to make DNA and RNA, so it cannot replicate. Healthy body cells can manufacture their own asparagine; tumor cells cannot. Because of this, L-asparaginase preferentially targets tumors without damaging other body cells.

L-asparaginase is used to treat lymphoma and lymphoid leukemia. It is given as an injection, typically into the muscles or under the skin (not as an IV injection). Dogs tolerate Elspar very well. It does not cause low cell counts, unless it is given with vincristine, and side effects, such as nausea, vomiting and diarrhea, are uncommon and usually mild.

There are a few important side effects to consider when using L-asparaginase. The first is anaphylaxis (allergic reaction). When an allergic reaction occurs, it usually happens after repeated treatments, and within thirty minutes after the treatment has ended, so your dog must be monitored for swelling, red skin and itchiness after receiving L-asparaginase. I keep my patients for observation for 30 minutes after treatment and also give antihistamines and/or steroids before treatment to counteract allergic effects. Anaphylaxis is rare, but the risk increases with repeated doses. (I use this agent often, and I have never had an episode.)

Pancreatitis, or inflammation of the pancreas, is another rare side effect to watch for. Your dog may be at risk if he has ever had pancreatitis before, so monitor your dog at home for symptoms such as abdominal pain, nausea, vomiting and fever. Call your vet immediately when any of these signs develop.

In a few cases, abnormal blood clotting (too much or too little, depending upon the case) can be a problem with L-asparaginase, particularly if your pet has clotting issues related to lymphoma.

Plant alkaloids are often used in chemotherapy treatments. They are sometimes referred to as vinca drugs because they are commonly derived from the periwinkle plant (vinca is the Latin name for periwinkle). Plant alkaloids disrupt the cell’s ability to divide by interfering with the mitosis phase of the cell cycle.

Vincristine is the most commonly used plant alkaloid. Lymphoma and some sarcoma protocols combine it with other drugs, while transmissible venereal tumor protocols use it as a single agent.

Side effects like nausea, vomiting and diarrhea are usually mild, as is constipation, and vincristine is typically tolerated well. Bone marrow suppression and hair loss are not common side effects, although they can occur.

Vincristine is metabolized in the liver and excreted in the bile, which exits the body in the feces, so make sure you clean up after your dog carefully, according to the safety instructions on
page 134
. If your dog has a liver condition or disease, the dose of vincristine may need to be significantly lower, so check with your vet or oncologist, if this is true for your dog.

Like doxorubicin, vincristine is toxic to tissues when not injected directly into a vein. Though the damage it causes is typically not as severe as that of doxorubicin, it can still be severe enough to warrant extreme caution on the part of your vet or oncologist.

Vincristine occasionally damages the nerves, causing a condition called peripheral neuropathy, or temporary weakness and wobbliness when trying to move or stand.

Another commonly used plant alkaloid is vinblastine, which is often used in lymphoma and mast cell tumor protocols. Much like vincristine, vinblastine can cause tissue damage when not injected directly into the vein.

Unlike vincristine, vinblastine can suppress the bone marrow, so follow up appointments to draw blood and run a CBC are very important. Other side effects include nausea, vomiting, diarrhea, loss of appetite and hair loss. Because vinblastine is metabolized by the liver and excreted in the feces, be very careful cleaning up after your dog and follow the safety instructions in
Chapter 11
. Your vet or oncologist may need to reduce your dog’s dose if she has a liver condition.

Vinorelbine (brand name Navelbine) is another plant alkaloid from the vinca family. It’s a newer drug, a “second generation” vinca drug (which means that it is a refinement of the first generation drugs like vincristine and vinblastine), and is particularly useful for lung tumors. It is metabolized in the liver, so your dog’s doses may need to be reduced if he has a liver condition, and you must be extra careful when cleaning up after him.

Like its older sister drugs, vinorelbine is a severe vesicant, which must be injected directly into the vein to avoid tissue damage. Other side effects can include hair loss, nausea, vomiting, diarrhea and bone marrow suppression.