The Dog Cancer Survival Guide (123 page)

Another group of chemotherapy drugs is platinumbased. The beautiful white metal can be compounded (mixed) and administered as a fluid, directly into the vein. These drugs create cross-links, or bind strands of DNA together, so that they cannot separate from each other later during cell division. The two most common platinum compounds are cisplatin and carboplatin.

Cisplatin can be used to treat osteosarcoma, some carcinomas (including squamous cell carcinoma), bladder tumors, and nasal cancers. This is a very toxic chemotherapy drug, and I personally do not use it in my practice because of its severe toxic side effects, the complexity of its administration protocol, and my worries about staff safety.

Administering cisplatin is a daylong process. Beforehand, a CBC will be performed to check for normal blood cell counts. Cisplatin is hard on the kidneys, so the oncologist will also check the kidney markers and get a urine sample to see its concentration. If the bone marrow and kidneys seem able to handle the treatment, IV fluids are given at very high rates in order to cause diuresis, or increased urine production through the kidneys. Cisplatin is excreted in the urine, so these extra fluids (given both before and after treatment) keep the drug from resting in the kidneys and causing irreversible kidney damage, which is one of cisplatin’s worst side effects.

Both because of the diuresis and the cisplatin, dogs urinate a great deal during and after treatment, which is why hospitals must keep the dog in a special cage that drains urine away. Staff must be very careful not to touch this urine directly, as it is toxic.

Cisplatin is not a particularly expensive drug, but the intensive procedures and the other medications needed to administer it can make it expensive to use.

In addition to the need to void large fluid volumes for hours on end, dogs also experience nausea and vomiting during treatment. Anti-nausea and antivomiting drugs are a required part of the protocol to counteract these side effects.

In addition to these side effects, some dogs experience severe bone marrow suppression. Hair loss may also occur, and nerve damage in the ear may (rarely), too, which results in permanent hearing loss and/or loss of balance and wobbliness while walking.

For all of these reasons, I prefer carboplatin when a platinum-based chemotherapy drug is needed.

Carboplatin is used to treat sarcomas, including osteosarcoma, and some carcinomas. It’s a newer platinum-based drug with fewer and much less severe side effects than cisplatin. It is expensive (although not as expensive as it once was); on the other hand, it doesn’t require daylong hospitalization, extra staff or extra IV fluids.

Carboplatin is an IV drug. It can also be injected straight into the chest or abdominal cavity, which is sometimes helpful for dogs with large effusions accumulating in either cavity.

Unlike cisplatin, carboplatin does not directly damage the kidneys, does not cause vomiting during administration and does not require an extensive diuresis procedure. It takes ten to fifteen minutes to inject the drug, making it a much less intense than cisplatin.

The main side effect is bone marrow suppression, especially the white blood cells and platelets. While most chemotherapy drugs show bone marrow suppression after seven days, carboplatin takes ten to fourteen days. Checking on the bone marrow with a CBC is a standard follow up, as is monitoring your dog at home for easy bruising or bleeding problems. Your oncologist may also recommend antibiotics (see the doxorubicin section for details).

While carboplatin does not directly damage the kidneys like cisplatin does, it is ultimately cleared from the body through the kidneys and the urine. If your dog has kidney problems, your oncologist will likely reduce the dose to decrease the chance of side effects.

Tyrosine kinase inhibitors, also known as TKIs or c-Kit inhibitors, are a relatively new class of drugs that offer targeted therapy. While most of the drugs we’ve talked about so far kill all rapidly dividing cells – including normal cells – TKIs target cells with specific mutations, or with abnormal proteins found only in some cancer cells. They leave most normal cells alone.

There are variations among TKI drugs and, therefore, differences in their effect on different patients’ tumors. Three TKIs have been successfully used in dogs: imatinib (brand name Gleevec), masitinib (brand name Kinavet CA-1) and toceranib (brand name Palladia).

We are starting to use TKIs in combination with more traditional chemotherapy drugs. The hope is that, by giving them at the same time, or in alternating rounds of therapies, the more specific actions taken by TKIs will kill more tumor cells, help inhibit new blood vessel formation and increase the length of remissions. Of course, more drugs mean more potential toxic side effects, so this decision must be made carefully and on a case-by-case basis.

Palladia is the first chemotherapy drug approved by the FDA specifically for use in dogs (all other chemotherapy drugs are human drugs that we have learned how to use effectively in dogs). Palladia is approved for mast cell tumors, specifically those of grade II and III, with or without regional lymph node involvement. Any other use of Palladia is technically off-label (but as always, vets can prescribe any medication for any condition they judge safe and appropriate).

Palladia targets mast cell tumors in two ways: it kills them directly by targeting the mutation, and also inhibits their ability to build new blood vessels. When looking at all of the original safety and efficacy trials as a whole, about 60% of the dogs experienced their mast cell tumors disappearing, regressing or stabilizing. Their overall health was also improved.

It is unlikely that one drug is all a dog needs to fight cancer. We must attack from different angles, using drugs with different mechanisms. For most MCT patients, I recommend a protocol that uses Palladia with other MCT drugs. These protocols are now being developed, evaluated, and optimized.

Palladia comes in pill form and is administered at home, usually every other day; it is still a powerful chemotherapy agent. Its use requires office visits, so your vet or oncologist can monitor your dog for problems. Regular visits, particularly for the first six to eight weeks will include full physical examinations, monitoring of body weight changes, blood work including CBCs and chemistry panels, and a fecal test for blood in the stool.

The most common side effects dogs experience on Palladia are nausea, vomiting and diarrhea. Lack of appetite, lethargy, lameness, weight loss and perforations (ulcers) in the stomach or intestines have also been reported. To detect a perforation, look for black or tarry feces and/or blood in the feces or vomit. Side effects can be serious, and when this or any other symptom is experienced, stop Palladia immediately and call your vet for advice.

It should be noted that most side effects occur within the first six weeks, and your oncologist may need to make dose adjustments, or even take a break for a week or two. In my own practice, I can find the right dose for the majority of dogs. Dogs are usually on Palladia for a minimum of six months, but I have managed some patients on the drug for greater than a year.

While Dr. Dressler has heard some real horror stories from readers about Palladia, I have found it to be no more problematic than other chemotherapy drugs, especially when handled by an experienced oncologist. I recommend watching your dog closely for side effects, committing to regular office visits, and asking your vet for advice on how to manage your dog proactively. It’s a good idea to discuss possible side effects before you start Palladia, so you can really understand what to look for. Palladia must be handled very carefully according to the safe handling instructions in
Chapter 11
.

I am very excited by the addition of this drug to our arsenal. Although it was approved specifically for MCT, oncologists including myself have used Palladia to treat other cancers, with promising results. Palladia’s anti-angiogenic effects make it an excellent candidate for metronomic chemotherapy (see
page 137
). Data presented recently at the annual Veterinary Cancer Society meeting demonstrated its efficacy in OSA, anal sac carcinoma and thyroid carcinoma. As we continue to use this drug, we’ll find out more about its potential for both traditional and metronomic chemotherapy.

Another tyrokinase inhibitor is masitinib (brand name Kinavet CA-1). Masitinib is a new drug in the United States (conditionally approved by the FDA in December of 2010), which had already been approved in Europe for mast cell tumors. Masitinib targets some of the same tyrosine kinase receptors (c-Kit) Palladia does, and also some cell structures involved in angiogenesis. Masitinib has been safely combined with other traditional chemotherapy drugs, when used in Europe (or in the U.S. through the FDA’s compassionate use program). It has similar side effects to Palladia, including vomiting, diarrhea, low blood cell counts, low blood proteins and increased liver markers. Dogs sometimes develop resistance or intolerance to Palladia, in which case they may be helped by masitinib.

You may have heard of Gleevec, the brand name version of imatinib; in 2001 it was approved for use in humans for chronic myeloid leukemia (CML), a cancer of the white blood cells. This TKI targets an abnormal cellular protein, present in nearly all CML patients, called BCR-ABL. When normal, BCRABL is much less active than in the mutated form found in CML patients. This mutation seems to be involved in CML, and blocking its activity helps kill the leukemia cells. In 2002, Gleevec was also approved to treat a rare form of stomach cancer in humans, called gastrointestinal stromal tumor (GIST). Gleevec can also be used to treat mast cell tumors in dogs. It has similar side effects to Palladia, including vomiting, diarrhea, low blood cell counts, low blood proteins and increased liver markers.

Corticosteroids (cortisol-based hormones) are often used in chemotherapy protocols. Many protocols use them in combination with other drugs.

The steroid prednisone is converted to prednisolone in the liver. It can be used alone for lymphoma treatments, or in combination with other drugs in chemotherapy protocols.

Prednisone/prednisolone is an anti-inflammatory, which is why it can be so effective in treating cancer. As cancer creates inflammation in and around the tumor, reducing it often makes your dog more comfortable.

Prednisone is inexpensive, especially compared to other chemotherapy drugs, and it is used to treat many other diseases and conditions, so it feels familiar to many owners. Unlike other chemotherapy agents, prednisone can be handled with bare hands and does not make your dog’s leavings toxic. It can be given at home in pill form. Prednisone does have a lot of side effects, which are usually mild, in comparison to other drugs used for cancer.

The most common and expected side effects include excessive thirst, urination and appetite. There can also be dark or black stools from stomach ulcers, loss of muscle, and immune suppression, which can leave your dog open to infections. Some dogs also experience increased panting. Long-term use can cause thinning of the hair and coat, changes in the skin color, and a “pot-belly.” Other problems that can happen over time include diabetes, liver problems, kidney problems, and muscle loss or wasting, so it is best to limit its chronic use.

Prednisone should never be combined with other anti-inflammatory drugs like aspirin, ibuprofen, any other NSAIDs (non-steroidal anti-inflammatory drugs), carprofen (brand name Rimadyl), meloxicam (brand name Metacam), deracoxib (brand name Deramaxx), Tylenol with codeine, other corticosteroids like methylprednisolone or budesonide, or piroxicam (brand name Feldene). This is because all of these drugs have a potential to cause stomach ulcers, and combining any of them with prednisone can increase that risk. Using Apocaps with prednisone warrants special instructions, which can be found on
page 169
.

Another consideration, when using prednisone, is the potential necessity to taper off usage. After seven days of using prednisone, the body significantly decreases its own corticosteroid production. If prednisone is stopped abruptly, the body can be thrown into a kind of shock, with symptoms like nausea, vomiting, weakness, pain and fever. Tapering the use of prednisone, however, allows the adrenal glands (which produce corticosteroids) to gradually increase steroid production. This helps your dog’s hormones to stay in balance. The longer you have used prednisone, the longer the tapering period, so check with your vet or oncologist.

Prednisone can be a very good, inexpensive option for some owners, although its use is complicated by many factors. Make sure you and your vet take all of your dog’s health conditions into account as you decide whether to use prednisone.

Piroxicam (brand name Feldene) is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used in vet practices as an anti-inflammatory, for pain relief and to reduce fever. It is prescribed as an anticancer agent for transitional cell carcinoma and oral squamous cell carcinoma.

Piroxicam inhibits the growth of some tumors, apparently by shutting down an important enzyme called cyclooxygenase (COX-2). COX-2 converts certain acids into prostaglandins, which are known to promote tumor cell growth. They also promote the development of new blood vessels and immune suppression, which allows tumors to thrive. By inhibiting COX-2, prostaglandins are inhibited, so tumor growth can be slowed.

Piroxicam can be given at home in pill form and is not toxic to handle.

When piroxicam is used, it’s important to monitor your dog for ulcers and gastro-intestinal bleeding. These symptoms include decreased appetite, vomiting (with or without blood), black and tarry stools, and diarrhea. If any of these symptoms crop up, stop giving piroxicam and call your vet or oncologist. The problems usually end soon after medication is stopped, but some temporary medications may be prescribed to help the ulcers heal.