The Dog Cancer Survival Guide (121 page)

Cyclophosphamide (brand name Cytoxan) is the most common alkylating agent. It is used most commonly for lymphoma, and also for lymphoid leukemias, carcinomas, sarcomas and some autoimmune disorders. While most chemotherapy drugs come in just one form, cyclophosphamide comes in both an injection and a pill form.

Cyclophosphamide needs liver enzymes to “turn it on” before it becomes an active chemotherapy agent. If your dog has severe liver disease, she may not activate enough of the drug to produce an effective dose, which is a factor your vet or oncologist will likely take into account, when including it in your protocol and choosing a dosage.

Common side effects of cyclophosphamide include hair loss, nausea, vomiting, diarrhea and bone marrow suppression. Dogs on cyclophosphamide must be encouraged to urinate frequently for the three days after treatment, in order to clear the by-products from their urinary system. For this reason, it’s commonly given in the morning (if you’re using the oral form at home, make sure to give it early in the day) to allow for daytime urinations. Dogs will not necessarily feel the urge to urinate, so you should encourage your dog to relieve himself frequently, especially right before bedtime, for the next three days.

These frequent walks are necessary to prevent sterile hemorrhagic cystitis (SHC), which develops when one of the by-products of cyclophosphamide, acrolein, irritates the bladder, and 9% of dogs develop this condition. SHC is irritating and causes your dog to void small amounts, much more often than usual and sometimes pass blood in the urine. When your dog develops these symptoms, a urine test and urine culture must be run to rule out a possible bladder infection. When a bladder infection is present, the culture will show which antibiotic is needed; when there is no bladder infection, the irritation is probably due to the cyclophosphamide, which should no longer be used (chlorambucil is the typical replacement).

To further reduce the risk of developing SHC, I recommend pre-treating with a diuretic to help increase the output of urine. For example, an injection of furosemide (Lasix) decreases the risk of SHC to only 1.2%.

It is also important to keep your dog from dehydrating from urinating so often. Give your dog extra water and keep the bowl full. Also, be particularly careful to clean up urine, if your dog has an accident in the house.

Chlorambucil (brand name Leukeran), another alkylating agent, is most commonly given for small cell (low grade) lymphoma, chronic lymphocytic leukemia and, occasionally, mast cell tumors. It is also used as a replacement for cyclophosphamide, when SHC develops. This is an oral medication, typically given regularly (daily or every other day), at home, by owners.

Compared to other drugs, chlorambucil is minimally toxic. Most chemotherapy drugs cause bone marrow suppression within seven to fourteen days; chlorambucil has a much slower effect – it often takes months for symptoms to show up, and then the bone marrow can take weeks or even months to return to normal function. Because of this slow effect, routine follow up (usually every other week for the first two months, and then every four to six weeks) is important: to monitor for bone marrow suppression and to correct problems as they arise. These follow-ups must include a blood draw for a complete blood count (CBC).

Chlorambucil comes in tablets and is given by owners at home, every day or every other day, depending upon the prescription. In addition to bone marrow suppression, it can cause hair loss and, sometimes, nausea, vomiting and diarrhea.

No chemotherapy drug is safe for use in pregnant dogs. This is because the developing fetus in the womb is full of rapidly dividing cells – which are vulnerable to the chemotherapy.

There are several common and expected side effects associated with chemotherapy drugs. Most dogs will experience mild digestive upset (vomiting, nausea or diarrhea), at least once or twice during the course of a typical chemotherapy protocol. This usually clears up easily on its own or with supportive at-home medications. In fewer than 5% of dogs, these symptoms may be so severe that dogs will require hospitalization for IV fluids, antibiotics and injectable anti-nausea drugs. Detailed information on how to manage these side effects is included in
Chapter 11
.

Remember: many chemotherapy drugs lower the levels of white blood cells, thereby suppressing immunity. Unless this suppression is very severe, most dogs do not have any symptoms associated with immunosuppression. Even so, it is important that your dog’s blood be checked before every chemotherapy session and sometimes during follow-up visits. A complete blood count will show your oncologist how your dog is doing and help him calculate the best dosage of chemotherapy. See
Chapter 11
for more details on chemotherapy.

In addition to a CBC, depending upon the drug involved, your oncologist may need to run other tests (for example, for liver or kidney values), before starting a chemotherapy treatment.

Lomustine (also called CCNU) is an alkylating agent used to treat mast cell tumors, some brain tumors, and lymphoma that has relapsed. It belongs to a unique group of drugs which can cross the brain’s barrier (called the blood brain barrier) and get directly to the nervous tissue. Because of this ability, it may also be useful for lymphomas involving the brain and spinal cord.

This potent drug can cause vomiting, nausea and diarrhea. It can also cause severe bone marrow suppression, including very low white blood cell counts, usually seven to fourteen days after administration (these may not occur until after multiple doses, so blood counts must be monitored as treatments progress).

High doses of lomustine have led to liver damage in a small number of dogs, so I always check liver values before I administer a dose. Signs of liver damage are typically non-specific or vague, and can be similar to other chemotherapy side effects, including lethargy, loss of appetite, vomiting and diarrhea. (Call your vet immediately if you notice severe symptoms.) Most dogs recover from the liver toxicity, but the drug will typically need to be discontinued. Recent preliminary research suggests that using Denamarin (a liver supplement that combines Denosyl, also known as SAM-e, with milk thistle) may decrease the issue of elevated liver values and allow for more Lomustine doses. I use this supplement with my patients.

In a recent report, Lomustine used in a metronomic protocol (frequent, daily small doses given with no extended rest periods), was shown to avoid the SHC associated with chronic cyclophosphamide use. This protocol was generally well tolerated, with 27% needing to stop due to side effects. Fifteen percent developed elevated kidney values, and 21% developed elevated liver values, so these organs need to be closely monitored with blood work. Complete blood counts are also important, as is monitoring for gastro-intestinal side effects. Specific metronomic protocols, including tumor types, doses, and schedules, are still being developed.

Lomustine comes in capsule form only, and can be given at home, with the blood work checked and approved just before each dosing. Its potency makes it very dangerous, so be sure to follow the side effect management advice, detailed in
Chapter 11
. Give lomustine on an empty stomach, several hours after a meal, to reduce nausea and vomiting.

Mechlorethamine (brand name Mustargen) is an alkylating agent and one of the original chemotherapy drugs. It’s derived from mustard gas and often used in combination with several other drugs in the MOPP and MVPP protocols used to treat lymphoma (typically relapsed lymphomas).

Mustargen must be handled with great care, because it is a severe vesicant, which means that it has an extreme damaging effect on tissues, when it gets outside the vein during administration. It comes as an injection only, and must be given at the vet hospital by staff experienced in handling and using this specific drug. A carefully placed catheter must go directly into a vein, and great care must be taken to inject mechlorethamine directly into the vein, so that it does not damage other tissues. When it comes in contact with other tissues, there can be serious irritation. Other side effects include nausea, vomiting, diarrhea and low white blood cell counts.