Understanding the Treatment Process II:
Drugs and drug protocols
This chapter discusses some of the most common chemotherapy drugs, how the drugs are administered, commonly reported side effects and reactions, and observations based on our experience. This is the most technical part of the book, and I have limited it to compiling basic information available from multiple sources including our VHUP discharges, veterinary hospital websites, and other materials.
How Chemotherapy Drugs Work
Chemotherapy works by attacking and killing rapidly dividing cancerous cells. Unfortunately, the drugs used in treatment generally can’t distinguish between cancer cells and other fast growing cells in your dog’s body. As a result, fast growing cells needed for other vital processes may be affected. In particular, your dog’s bone marrow, the site where new red and white blood cells and platelets are produced, and his gastrointestinal tract, may be adversely affected by chemotherapy (See "Side Effects", below). Effective chemotherapy is a balance between killing cancer cells and not killing too many other cells that are needed to support your dog’s vital organs.
The chemotherapy drugs affect the process of replication of rapidly dividing cells by interfering at the most basic cellular level with their DNA or RNA. (See http://www.cvm.tamu.edu/oncology/glossary/glossary.html ("chemotherapy"), also http://www.perseusfoundation.org/oc.html (p. 49, Indications and Toxcities of Selected Antineoplastic Agents) . Different drugs may work in different ways, or on what are believed to be different sub-groups of cancer cells. This is why many treatment programs or "drug protocols" rotate drugs frequently. This is sometimes called "combination chemotherapy", as opposed to "single agent" chemotherapy in which just one drug is used.
What is a drug protocol?
A drug protocol is a group of drugs, selected for their differing and complementary cancer fighting properties, administered in a particular order and on a pre-determined schedule, to treat lymphoma. Most (but not all) protocols either administer multiple drugs simultaneously or rotate drugs frequently. This is done for two reasons. The first is that use of multiple drugs or rotating drugs reduces the likelihood of the cancer becoming resistant. The second is that rotation can help avoid side effects from cumulative use of a single drug. A "cycle" is a completed sequence of all of the drugs in the rotation. Depending on the number of drugs in your dog’s protocol and the spacing of treatments, a cycle may take a month to three months to complete. A useful discussion of drug protocols is at: http://www.vetmed.lsu.edu/oncology/lymphoma1.htm
Many canine lymphoma protocols include some combination of vinblastine/vincristine, Cytoxan (cyclophosphamie), Elspar (L-asparaginase), Adriamycin (doxyrubicin), and prednisone. http://www.oncolink.upenn.edu/experts/article.cfm?c=3&s=32&ss=86&id=1788
The carefully selected group of drugs is given in a precise combination and rotation on the theory that some kinds of cancer cells will be killed by one or two of the drugs while other cancer cells will be killed by the other drugs. In addition, some drugs act together so that the combined effect of the two is greater than that of each if given separately.
Certain standard protocols have names. There are the Wisconsin protocol, COP, CHOP, etc. You may want to ask your oncologist the name of the protocol that is used for your dog – this makes it easier to access literature and do internet research. A useful article discussing some different protocols and factors influencing survival is at http://www.vetmed.lsu.edu/oncology/lymphoma1.htm
Is there an ideal protocol? How does the oncologist select one?
If you surf the net, or talk to other oncology clients in the waiting room of a hospital such as VHUP, you will encounter other owners whose dogs are in treatment for lymphoma, perhaps even the same type that your dog has. You will learn what drugs, and in what sequence -- different treatment "protocols" – are being used for other dogs. Another dog’s protocol may be different from yours, and you may worry: "Is my dog receiving the "right one" for his disease?" We had this question in our minds as we did reading and searched the internet, and realized that Adriamycin (doxyrubicin), characterized by some sources as the wonder drug of chemotherapy, was not in Berry’s protocol.
The answer is that a canine oncologist will select a protocol based on his or her training, experience, and professional perspective; on your dog’s particular type of lymphoma; and, as time passes, on the nature of the drugs themselves, and the reactions, if any, your dog and your dog’s disease have had to the drugs previously used. A protocol should be selected that provides the best opportunity to successfully treat your dog’s disease, coupled with as few risks of serious complications as possible. We have never seen Berry’s precise protocol reported in anything we have read, but it was obviously highly effective for him –3 ˝ years of good days.
Be aware that different veterinary research or teaching hospitals may have different theories about what sorts of protocols work best. This may be based on research they have performed, or their clinical experience with relative survival times in different protocols. But it is important to understand the protocols that other oncologists or facilities are using, and question your oncologist about differences and choices. That said, there is probably no "ideal" protocol that works for all dogs or all lymphoma. Berry’s two major protocols, each of which lasted 18 months, were very different, but each was highly effective for him. The first was a schedule of three frequently rotated drugs, plus prednisone. The second involved only one drug plus prednisone.
Most protocols begin with higher, more frequent doses of drugs. Intensive therapy is needed at the outset to beat the cancer back. But four to six months after commencement, your dog may become less able to tolerate the cumulative effect of the drugs, so the frequency is reduced.
How dosages are determined
Dosages of drugs must be high enough to be medically effective but not so high as to cause unnecessary damage to healthy cells in the body. A helpful discussion of the relationship between killing cancer cells and damage to other body systems is at: www.cvm.tamu.edu/oncology/faq/questions/chemo02.htm
Based on our experience at VHUP, initial dosages are based on general rules – in some cases your dog’s weight -- but there is no precise scientific formula to tell the oncologists how your dog will react. Initial dosages may be adjusted downward based on the reaction of the individual dog and the cancer but will still be effective. Berry’s initial dose of Cytoxan and his course of vincristine therapy were at reduced levels from that initially prescribed, but it did not affect his remission times. Unfortunately, this aspect of treatment seems to be a sort of educated "trial and error". This is one of the areas where the uniqueness of your dog comes into play: different dogs have problems with different drugs, and some dogs don’t have any problems at all.
What about delays in treatment?
Blood tests performed prior to a scheduled treatment may reveal that your dog’s white blood cell count is too low for chemotherapy that day. In some cases, delay does not affect the overall outcome. Berry’s first Cytoxan treatment in 2000 was administered a week late, and his second Lomustine treatment was delayed a week in 2003 due to a campylobacter infection; neither delay seemed to have any negative impact. On the other hand, in the last month of Berry’s life, when we were forced to delay his Lomustine treatment, his lymph nodes rose immediately -- one of a complex of health problems that signaled the end was near.
Protocols from Berry’s Chemotherapy
Berry’s first protocol (February 2000 – August 2001):
Elspar (10,000 IU) (injection), vincristine (.6 mg) (IV drip), cytoxan (75 mg pills for 4 consecutive days), vincristine (.6 mg) (IV drip); prednisone (a declining dose over time)
He received one drug weekly, in rotation, from February 18, 2000 until June 8, 2000 (4 months), then one drug every other week until March 2, 2001 (8 months), then one drug every third week until August, 2001 (six months), at which time chemotherapy was terminated. The vincristine dosage was .8 mg on the first administration, but Berry experienced side effects, so it was cut to .6 mg for subsequent administrations. Later, as Berry regained lost weight, the dosage was increased to .65 mg.
Prednisone. As initially prescribed: Two 20 mg tablets each day for 2 weeks, one 20 mg tablet each day for 2 weeks; one-half 20 mg tablet each day thereafter
As administered: Two 20 mg tablets each day for 2 weeks; one 20 mg tablet each day for 4 months; two 20 mg tablets every other day for 4 weeks; one-half 20 mg tablet every other day for 8 weeks
Berry’s second protocol (January 2002 – June 2003)
Leukeran - 2 mg tablets. 3 once daily for 10 days, then reduced to 2 once daily alternating with 1 daily for a year; then reduced to: 2 once daily, skip a day, 1 daily, skip (sequence repeated for 6 months).
Prednisone – 20 mg. 1 ˝ tabs daily for 7 days, 1 daily for 7 days, ˝ daily for 7 days, then ˝ every other day.
Berry’s third protocol (June 2003 – August 2003)
Lomustine (CCNU) 75 mg every three weeks. His second Lomustine treatment was delayed one week due to an unrelated infection.
You will hear the doctors discuss "rescue protocols". These are drug programs, generally consisting of a combination of drugs, that are used when your dog has come out of remission, to attempt drive the cancer back under control and attempt to achieve remission again. A site discussing rescue protocols for treatment of mast cell tumors at http://www.vetmed.ufl.edu/sacs/Oncology/treatmentprotocols.htm discusses some rescue protocols for canine lymphoma. Choice of a rescue protocol is influenced by a number of factors. If your dog is currently in a drug protocol that is not containing the cancer, different drugs will be chosen. Prior adverse drug reactions obviously influence the selection, as may cost and scheduling.
Technically speaking, Berry’s treatment never used a rescue protocol. Each time he came out of remission, he was receiving little or no chemotherapy, so he really just went back into a regular treatment regimen. If your dog is in the later (maintenance) phases of a protocol, he may just be placed on a different drug as Berry was in January 2002 and June 2003, rather than a rescue protocol.
On December 16, 2001, about four months after Berry had stopped chemotherapy, we noticed blood in his urine and immediately took him to VHUP. He was ultimately diagnosed with a benign sterile cystitis (probably a delayed reaction to the Cytoxan he had regularly received in his first chemotherapy protocol). But the veterinarians who examined Berry also grew concerned that he might be coming out of remission, and in early January 2002, the pathologists made the diagnosis that Berry was out of remission. Leukeran and prednisone, both given in pills, were prescribed. Berry did well on this therapy, with no side effects, and the small pills were a wonderfully non-intrusive medication. The second time Berry came out of remission he was again borderline. So, we don’t think these were technically "rescue protocols". In neither case was an effort made to hit the cancer with a big wallop of drugs, or to use the drugs like doxyrubicin that are saved for the really tough times; it was more like Berry just switched chemotherapy.
Drugs used in Treatment of Canine Lymphoma
There are many drugs used in canine chemotherapy, but the core group is relatively small. These drugs are called "antineoplastic agents". This means they prevent the development, growth, or proliferation of malignant cells. Several of the drugs are the same drugs used in human chemotherapy. A technical chart describing these drugs is located at http://www.vet.purdue.edu/vcs/Pcop/chemotherapyinfo.htm. Information about the various chemotherapy drugs can be located through web searches for pet information such as http://www.veterinarypartner.com/Content.plx?P=SRC&S=1&SourceID=52, and on some of the teaching hospital sites listed in Appendix II. From an owner’s perspective, the most important aspect of how these drugs disrupt cancer cells is what that implies for the healthy cells in your dog’s body. In other words, what are the negative effects of the drugs.
Drugs used in Berry’s Treatment
Elspar (L-asparaginase). This drug is a protein type drug. Elspar works by depriving cancer cells of an amino acid "asparagine, " which is required by the cancer cells to continue to grow. Elspar is delivered in a simple, subcutaneous (under the skin) injection. Unlike most of the other chemotherapy drugs, Elspar does not suppress production of cells in the bone marrow. Because Elspar is a protein drug, it can produce a sudden, anaphylactic allergic reaction in the first 24 hours after it is administered. We were told to bring Berry to the emergency service if his muzzle became swollen, or he pawed at his face or became agitated. Detailed information about Elspar is available at: http://www.marvistavet.com/html/body_l-asparaginase.html and at http://www.vin.com/petcare/articles/vethospital/m00938.htm
Cytoxan (cyclophosphamide). Cytoxan is an alkylating agent that interferes with the replication of cells. It is a nitrogen mustard and is related to gases used in chemical warfare. Cytoxan is given in pills, which must be handled with extreme care. Cytoxan is an inactive drug in the capsule. It is activated in your dog’s liver, where it is broken down, and then it is broken down again in the bladder. It is extremely important for dogs to receive ample water while on Cytoxan so that the drug wastes can be flushed out of your dog’s organs. Your dog also needs to be let out often to urinate while taking Cytoxan to remove the waste products from his bladder as quickly as possible. Detailed information about Cytoxan is available at: http://www.marvistavet.com/html/body_cyclophosphamide_.html
Leukeran (Chlorambucil). Leukeran is also an "alkylating agent" of the nitrogen mustard group. It prohibits cell replication so that cancer cells cannot reproduce. Leukeran is given in pills. Leukeran can cause a decrease in the white blood cell count so careful monitoring is needed. This usually occurs in the early weeks of treatment. Detailed information about Leukeran is available at: http://www.marvistavet.com/html/body_chlorambucil.html
Lomustine (CCNU). Lomustine is a member of the nitrosurea class of chemotherapy agents which acts by interfering with cell reproduction. Lomustine is not subject to multi-drug resistance; as a result, VHUP considered it a good choice for Berry’s third course of chemotherapy. Lomustine works more slowly than some other chemotherapy drugs and takes multiple administrations before it can be determined whether it is working to reduce the level of lymphoma. This made it a difficult drug from an owner’s perspective. We were worried that Berry did not seem to be improving, and wanted to know as soon as possible if the Lomustine therapy was working. As it turned out, he was not improving, but the problem was not his lymphoma. Detailed information about Lomustine is at: http://www.marvistavet.com/html/body_lomustine.html
Prednisone. Predisone is one of the mainstays of chemotherapy treatment. It kills cancer cells and also acts in concert with the other drugs. Prednisone is a steriod hormone. Prednisone is given in reducing doses during the course of chemotherapy. Detailed information about prednisone is at: http://www.marvistavet.com/html/body_prednisone.html
Vincristine and vinblastine. Both of these drugs are alkaloids derived from the vinca plant and are members of the "vinca alkaloid" class of chemotherapy drugs. Vincristine and vinblastine act by destroying fast growing cancer cells, but these drugs can also harm other fast growing cells in the body, notably in the bone marrow and the digestive tract. Veterinary oncologists have considerable experience with vincristine in animals, mostly with only minor side effects. It is also very sparing of the bone marrow. Some dogs experience delayed but dramatic reactions to vincristine. Vinblastine is easier on the gastrointestinal tract, but is harder on the bone marrow. Detailed information about vincristine is available at http://www.marvistavet.com/html/body_vincristine.html
Berry received vincristine, which is administered in an intravenous "drip", usually into a vein in the front or rear leg.
Other major drugs Berry did not use
Adriamyacin (Doxorubicin). Adriamycin works by impairing DNA and hinders cell division in cancer cells. This drug is commonly regarded as one of the most effective chemotherapy drugs, but it also is widely reported as having potential for significant harmful side effects. http://www.marvistavet.com/html/body_doxorubicin.html Doxorubicin has also been reported to be effective in inducing a second remission in dogs previously treated with combination chemotherapy. http://www.vetmed.lsu.edu/oncology/lymphoma1.htm
Berry did not receive this drug. Adriamycin can only be used a certain number of times without risking damage to your dog’s heart.
Drug Reactions and Side Effects
As discussed above, the manner in which chemotherapy drugs work can also result in damage to healthy tissues and organs in your dog’s body. This damage may occur shortly after administration of a drug, or later, based on the cumulative effects of a drug. A useful paper, "Indications and Toxcitities of Selected Antineoplastic Agent" at http://www.perseusfoundation.org/oc.html (page 49) categorizes the major short term ("acute") and long term ("delayed") medical side effects of the chemotherapy drugs discussed above. Our focus is to put some of the medical terminology into plain language and practical owner’s concerns.
Why do side effects occur?
As noted above, most of the chemotherapy drugs focus on reducing the cancer either by killing cancer cells or by preventing fast-growing cancer cells from reproducing. Unfortunately, the chemical attack of several of the principal drugs does not distinguish between cancer cells and non-cancer cells. Consequently, the destruction of beneficial fast growing cells in the bone marrow, and gastrointestinal tract is a concern. Chemotherapy drugs also can damage the heart, liver, kidneys, and bladder. This is the reason that blood samples and other diagnostic tests are performed to monitor the levels of blood components and organ function prior to administration of new chemotherapy. Finally, cells of hair follicles and cells in the reproductive tract can be affected – not life threatening to the family dog, but of concern to professionals who show and breed dogs.
An excellent general discussion of common side effects appears at "What are the Side Effects of Chemotherapeutic Treatment?" http://www.cvm.tamu.edu/oncology/faq/FAQ.html
Canine oncologists have considerable experience with the standard chemotherapy drugs and know how they affect dogs. Oncologists know whether a particular drug can be toxic, and what types of side effects may occur. What the oncologists cannot tell is whether your dog will be one of the dogs that experiences a particular reaction or side effect. Despite the generalizations that can be made, reactions and side effects vary widely among dogs. Happily, oncologists often are able to treat reactions and resolve side effects, by prescribing a counteracting medication, lessening drug dosages, or substituting other drugs.
What can you do?
Your job is to learn how drug reactions and side effects may present themselves so that you can watch for them. The timing of reactions and side effects also varies depending on the drug and your dog. Some reactions or side effects usually appear very soon after administration of the drug; others may take several days to appear. Some are most likely to occur the first time a drug is administered, while others may arise after cumulative exposure from multiple treatments. For example, with repeated use, Adriamycin can damage the heart muscle and Lomustine can suppress production of precusor cells in the bone marrow.
One of the more difficult issues for owners is that some drug reactions or side effects --– vomiting, diarrhea, weakness, lethargy, loss of appetite -- mimic symptoms of lymphoma or other cancers. This confused us in the first weeks of Berry’s treatment, when he experienced vomiting and dehydration following the first administration of vincristine in his protocol. Your dog, like Berry, may be in a weakened condition when treatment begins, without a lot of "reserves". At that point, it may be difficult for you (and sometimes the doctors) to determine whether further physical or behavioral changes in your dog are associated with the disease, or side effects of treatment. Similarly, toward the end of our dog’s life, we were unsure whether Berry’s symptoms were caused by deteriorating health or by his new chemotherapy.
In our experience, symptoms are hardest to evaluate during the initial phases of a protocol or first use of a drug – when you have no benchmarks to use. The initial administration of a drug may produce side effects that are very distressing and make you question whether or not to continue treatment. But the side effects may be manageable, or it may be possible to reduce the chemotherapy dosage to a level that is still effective for your dog, or to substitute another drug.
Your job? To observe every detail of your dog’s behavior between treatments, to record that information, and to report accurately on the timing (onset and duration), and intensity of any side effects. To act quickly if your observations indicate immediate medical attention is needed. Otherwise, to try to be patient and give the drugs a chance to work.
Our advice? Educate yourself in advance about the possible side effects of every drug your dog will receive. Review those side effects with your oncologist and take steps to avoid the stress and costs of emergency care that can be avoided through care in diet, additional medications, and other precautions. Particularly with respect to potential GI side effects of vincristine, we would recommend that you ask the oncologist to prescribe metaclopramide so that you have it on hand if gastrointestinal side effects occur. The few dollars are well spent to avoid trying to explain your dog’s health status to a different veterinarian in an emergency care setting.
Nearly all of the most common chemotherapy drugs may cause nausea or vomiting. Below are some of the other particular reactions and side effects we were alerted might occur with the various drugs.
Elspar (L-asparaginase). Because Elspar is a protein drug, there is a chance of an allergic reaction occurring. This would typically in the first 24 hours after the injection is given, and could occur on the first dose or later administrations. We were told to watch for swollen muzzle or ears, pawing at the face, restlessness, agitation, or vomiting. Berry never had any reaction to this drug.
Cytoxan (cyclophosphamide). Other than nausea and vomiting, Cytoxan can cause severe bone marrow suppression, hair loss, and sterile hemorrhagic cystitis. One source indicates that up to 30% of dogs receiving Cytoxan for over 2 months develop bloody urine caused by excretion of the drug by-products. http://www.marvistavet.com/html/body_cyclophosphamide_.html
We were told by VHUP that in rare cases, a dog may have a traumatic reaction to Cytoxan, and be incapacitated for several days. More typically, we were told, Cytoxan can cause irritation of the bladder lining. This reaction, which may occur anytime during the week of Cytoxan treatment, mimics a bladder infection. Your dog may strain to urinate, or try to urinate repeatedly, or you may see blood in the urine. Make sure your dog drinks lots of water during the Cytoxan course of therapy and that he is able to go out frequently to urinate. This way, the drug by-products are removed from his body as soon as possible.
Our dog probably did not get out as frequently as he should have. Cytoxan had no ill effects on Berry while he received it regularly during his first 18 months of chemotherapy. However, he did develop cystitis several months after he stopped receiving the drug. Four months after Berry’s initial program chemotherapy was completed, we noticed fresh blood in Berry's urine and went to VHUP. Initially believed to have a bacterial infection, he was ultimately diagnosed with benign sterile hemorragic (bleeding) cystitis, probably a delayed reaction to the Cytoxan he had received in prior chemotherapy. The bleeding cleared up when our dog was put back on prednisone as part of his new chemotherapy protocol.
Leukeran (Chlorambucil). Leukeran can cause myelosuppression. Leukeran was a breeze for Berry. Leukeran can cause a decrease in the white blood cell count. Five months into his Leukeran therapy, VHUP reported Berry had "moderate lymphopenia", (mild anemia) but this was not apparent in his behavior and was never a problem. The pills, which he took in conjunction with prednisone, were easy to administer. Leukeran provided Berry with a sustained remission and high quality of life for 18 months. We don’t know if the Leukeran played any role, but during these 18 months Berry’s coat was at its finest. Although he had experienced a thinning coat in his first chemotherapy protocol, while on Leukeran, Berry’s coat was thick and luxuriant, his feather reached to the ground, and his tail was dubbed "the Plume".
Lomustine (CCNU). We were told by VHUP that Lomustine can affect the bone marrow, but more slowly than some chemotherapy drugs. This is called "cumulative myelosuppression". One source indicates that at least one in five dogs becomes neutropenic (lacking in white blood cells that destroy bacteria)) 5-10 days after Lomustine therapy. http://www.perseusfoundation.org/oc.html (p. 54). Also, reportedly rarer, VHUP indicated that Lomustine can damage the liver after multiple treatments.
We don’t really know how Lomustine affected Berry. He received the drug 3 times, and he seemed increasingly more lethargic as the course of therapy progressed. At first, we attributed this to the new, higher dose of prednisone in conjunction with the Lomustine. Then, his platelet count dropped and could not be replenished. At one point, VHUP theorized that by the third administration, in early September 2003, the Lomustine might be suppressing the production of megacareocytes (precursor cells in Berry’s bone marrow). But in the end the data were contradictory. Bone marrow aspirations indicated that the production of precursor cells was more than adequate – instead, the blood platelets were being destroyed – cannibalized – elsewhere in his body. Berry clearly had other significant health problems by this time.
Prednisone. Common side effects of Prednisone include increased appetite (a plus for lymphoma patients), thirst, frequent urination (oh, yes!), loose stool, and mild lethargy. Prednisone can also irritate the stomach, cause muscle wasting, delay wound healing, and have other immuno-suppressive effects. Prednisone also needs to be decreased gradually other health problems may occur. VHUP told us this when we considered stopping treatment early in Berry’s chemotherapy.
Berry was initially prescribed Prednisone at two 20 mg tabs per day for two weeks. The initial, high dosage of Prednisone made Berry urinate every 2-3 hours (hence, his nickname "Sir Peezalot"). Anticipate this possible side effect and plan for it – if someone is at home during the day, put your dog on a new schedule for very frequent trips outdoors. If this is not possible, plan to confine your dog in an area where he can urinate when he needs to without damaging rugs or floors. This problem will probably go away once the Prednisone dosage is reduced – usually in a matter of weeks, but in the early days of treatment, this temporary behavior can contribute to your feelings of frustration and loss of control as you repeatedly mop up dog pee.
Two more subtle changes related to Prednisone that we observed. The first is a general lethargy. This side effect was categorized by VHUP as unusual and seen only in the initial, higher dosage, however, during Berry’s first protocol, we found that each time the Prednisone dosage was reduced, Berry seemed to regain energy.
The second is deterioration of muscle mass when Prednisone is administered over a long period. VHUP described this to us as "pred head", their nickname for how the appearance of your dog’s head subtlely changes, looking a little pointy at the top. During Berry’s first protocol, we didn’t notice pronounced changes, although he did seem to have more difficulty jumping into the car. But during Berry’s third protocol, what we and VHUP thought was "pred head" was probably actually muscle depletion from other causes, not the prednisone.
Vincristine and vinblastine. Vincristine is one of the drugs that can affect rapidly dividing cells in the GI tract. Dogs that receive vincristine may exhibit can have gastrointestinal side effects such as nausea, vomiting, diarrhea, constipation, and paralytic ileus (food failing to move through the intestine). These side effects are reported to be infrequent, occurring only at high doses, and generally within 48-72 hours after treatment. But they can occur later, and, in a small number of dogs, vincristine can slow or stop the passage of food through the stomach and intestines, temporarily disabling the digestive process.
We believe this is what happened to Berry in March 2000. Four days after the drug was first administered, Berry began pacing and could not settle down. Although the VHUP discharges instructed us to watch for diarrhea, with Berry, the reverse occurred: his stools became smaller and harder, and then stopped coming at all. Then vomiting began. Concerned that he needed to eat to withstand the rigors of chemotherapy, we tried to feed him, resulting in more vomiting. (Today we understand that water, not food, is critical.) Dehydration ensued, resulting in an Emergency Service trip for intravenous (IV) fluids. Because it was Berry’s second week of treatment, we didn’t know if these events were more likely a drug reaction, disease progression, or another, unrelated cause. VHUP’s Emergency Service didn’t know either, and believed Berry had an intestinal obstruction – the problem they see most frequently in the ER. Some veterinary sources refer to these episodes as "not unexpected" or dangerous, but our advice is to obtain the counteracting medicine before you go home – just in case!
Shortly after this crisis, we had our first formal consultation with the Oncology Service, and learned Berry had probably experienced a vincristine side effect – just later than typical. We were advised that when vincristine was next scheduled in Berry’s protocol, we could consider the possibility of substituting vinblastine. Vinblastine would be easier on the gastro-intestinal tract, we were told, but tougher on the bone marrow. VHUP ultimately recommended trying a reduced dosage of vincristine, coupled with metaclopramide, an anti-nausea medicine, and metamucil, to add roughage. This modification of the protocol worked well for Berry.
In addition to the short term effects of these drugs – such as the impact that a drug may have on the bone marrow a specific number of days following administration – cumulative long term effects may occur. As previously mentioned, this may occur with Adriamycin, Elspar, Cytoxan, and Lomustine after multiple administrations. Another possible long term effect is that your dog’s bone marrow may become "tired". This means it is unable to respond any longer to produce pre-cursor cells after being repeatedly forced to do so to replace blood components destroyed by prior chemotherapy treatments. The technical term for this situation is "myelosuppression."
The Relationship between Chemotherapy and other Treatments
If your dog is in chemotherapy treatment for any period of time, you may need to give drugs for other, non-cancer related reasons. These may be as basic as a flea and tick treatment purchased at a pet store, a monthly heartworm pill, or a prescription antibiotic for a hot spot. You will wonder what is and is not safe for your dog.
The answer lies with your oncologist. Always be sure to coordinate regular veterinary care with chemotherapy and to ask your oncologist (as well as your regular vet) about possible drug reactions/interactions. Your oncologist may suggest a different drug, or adjust the timing of giving it. We were always careful to ask, but I can’t recall that in Berry’s case any routine non-chemotherapy drug created a problem for him or his chemotherapy. However, we were instructed not to give Berry’s heartworm pill or a flea and tick treatment until at least 48 hours after a chemotherapy treatment was completed. During his chemotherapy, Berry received Baytril (campylobactor, diarrhea and blood in urine), Cephalexan (hot spots) Tri-top (hot spots), Ivermectin (scabies), Interceptor (heartworm), and Frontline(flea and tick), and Phenylpropanolamine (incontinence).
A related issue is whether to have unrelated surgery performed on your dog while he is in chemotherapy. This is a touchy question that I would answer differently today than a year ago. If the surgery is essential, you may have no choice. But more elective surgery is a harder call, and the costs and benefits should be weighed very carefully.
In February 2003, Berry had a small but growing non-malignant cyst removed from his eyelid and that went fine. But in the summer of 2003, we were faced with deciding whether or not to remove an ambiguous growth believed to be a spindle cell tumor, possibly cancerous, or pre-cancerous, on his elbow. We decided to proceed based on the idea that, if not removed, the tumor might spread locally (in a complicated area without "extra" tissue), or spread (metastacize) elsewhere. Berry seemed ok, although a little lethargic, and his blood values, etc. being measured by Oncology, were ok. We didn’t realize he was already failing.
While successful in removing the tumor, the surgery turned out to be much more invasive than we had understood— a large incision in a difficult area, and involving parts of the lymph system in his armpit. After the surgery, Berry expended precious resources trying to recover, had several trips to the Emergency Service, and he went into a rapid decline. His blood values declined rapidly and he never was able to receive chemotherapy again.
Hindsight is a great teacher. Today, we would try to be more deliberate and weigh the possible benefits against the risks. We would try to have a much clearer understanding of whether the tumor was likely to spread (or to have spread already – we later found two similar structures on his other side), and in what time period. If, for example, it was likely to take six months or a year for the tumor to create other problems, the odds were that Berry’s third remission wouldn’t last that long. So the risks on the other side were that the surgery itself would result in problems, or that even doing the surgery would not help. Berry was in his third round of treatment, and we knew that, for whatever reason, he was struggling somewhat. Pat, whose cat was also treated at VHUP, had a similar experience with a surgery.
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