Can’t you just give me the “chemo pill?”

I’ve been a major slacker lately when it comes to writing articles. I blame the fact that a few months back, the staff at PetMD cut back on asking me for contributions, therefore reducing my incentive (read: deadlines) for completing my tasks. My absence doesn’t stem from a lack of thought. I still possess a mind full of tangled deliberations and complicated goals. I’ve simply been depleted of the requirement to put fingertips to keyboard to iterate them intelligently.

One of the topics I’ve churned over and over in my mind is how best to educate owners who inquire about oral chemotherapy options in lieu of injectable treatments because they perceive the former as being less ‘intensive’, and therefore less impacting for their pet.

Countless times, owners ask me if I couldn’t just prescribe the “chemo pill” they heard about from one of several typical sources (insert any one of the following: primary veterinarian, friend, cousin, groomer, teenager worker at the pet food store, etc.) It’s funny, but in all my years of training as a medical oncologist, I never once learned about the “chemo pill”. I’m the first to admit, it would be remarkable if there was a pan-cancer tablet that effectively treated a multitude of tumors. Sadly, this magic bullet doesn’t exist.

After a few awkward seconds and a bit of further probing, I’m usually able to discern owners are asking about one of two oral chemotherapy options: Palladia ®, a tyrosine kinase inhibitor licensed for treating a form of skin cancer called mast cell tumors in dogs, or metronomic chemotherapy, which entails administration of low-dosages of chemotherapy drugs on a continuous basis to inhibit blood vessel growth to malignant cells.

Mainstream use of oral chemotherapy is a relatively recent development in veterinary oncology. For some cancers and the patients attached to those tumors, it can be an excellent treatment alternative. Research with a few specific cancers is available, and data is promising regarding its efficacy. However, evidence based information supporting a superior effect of oral protocols compared to well-studied injectable protocols is lacking for most cancers we treat. In fact, for most tumors, the efficacy of an oral protocols is, at best, theoretical.

Owners are attracted to the option of treating their pet with oral chemotherapy for several reasons. One of the major perceived pros is the incorrect belief that oral chemotherapy is less toxic than injectable treatments. This is a problematic thought process for two reasons: one is it perpetuates the overestimation of frequency and severity of side effects seen with injectable treatment and the two, it underestimates the potential negative effects of the oral drugs. Chemotherapy drugs, regardless of form of administration, carry narrow therapeutic indices, and their ability to induce adverse effects remains a major consequence of their administration.

The typical side effects of injectable chemotherapy include adverse gastrointestinal signs including vomiting, diarrhea, and/or poor appetite, and a temporary lowering of the recipient’s white blood cell counts. These signs are the same potential consequences of oral medications as well.

Another perceived benefit of oral chemotherapy is that treatment is less stressful for pets because it’s done at home, rather than at the hospital as is done for injections. While I cannot argue against the concept that pets, especially cats, are most comfortable in their familiar environments, the majority of animals remain absolutely calm during treatments. The process of administering intravenous chemotherapy is not stressful, and rarely do animals exhibit any distress from the process.  Many owners overestimate the degree to which their pets would be affected by the restraint required for injecting chemotherapy and assume the administration is in some way uncomfortable for them. In reality, this simply isn’t true.

A last area of misconception about oral chemotherapy occurs when owners mistakenly believe animals receiving this form of treatment do not require monitoring. This usually relates to the aforementioned goal of keeping things as low-stress as possible. It also relates to a perception that oral chemotherapy drugs are less costly than injectable ones. Owners are surprised to learn pets receiving oral chemotherapy are monitored closely as they are. For example, I recommend monthly exams and lab work for most patients. Therefore, owners must be aware that choosing an oral treatment plan doesn’t mean their pets are ‘off the hook’ from spending time at the veterinarian’s office. When you consider how little is known about the potential benefits of oral chemotherapy along with their relative newness, it makes sense that an oncologist would want to monitor your pet even more frequently than for a more well-established therapeutic plan. Cost-wise, all this monitoring means most oral chemotherapy plans are on par with injectable protocols.

What concerns me more than owners wanting to use oral chemotherapy are the primary veterinarians who offer such treatments rather than the standard of care injectable protocols because doing so requires no specific equipment or training in its administration. Injectable chemotherapy drugs pose health hazard risks to staff members if not properly drawn up in a biosafety cabinet and without wearing appropriate personal protective equipment and using a closed contained system. The physical act of injecting chemotherapy drugs requires advanced technical skills and experience. These fundamentals may not be present in a general veterinary hospital.

If a veterinarian discusses an oral chemotherapy plan, it should not be done under the guise of it being easier, less toxic, or less invasive. Especially if that veterinarian lacks the necessary training or equipment to successfully administer injectable drugs. A drug that is ‘easier’ to prescribe is not an appropriate substitute for a proven intravenous option for a particular diagnosis.

While I can comprehend why the idea of treating your pet’s cancer with a pill would, on the surface, seem like a simpler and less formidable solution, owner’s must be aware of the potential limitations and drawbacks to such a treatment plan. Consultation with a veterinary oncologist would be the most effective way to understand the available options and potential risks. To locate a veterinary oncologist near you, please visit www.acvim.org

When you can’t make up your mind…

During nearly every consultation, there comes a time where pet owners must make the decision whether to pursue chemotherapy or not. While a small number of people arrive assured that they will treat their pets, more frequently owners arrive with an open mind to the available options, searching for all possible choices before moving forward.

On rare occasions, at the onset of an appointment, an owner will inform me they have no intention of ever pursuing chemotherapy. I’m marginally astonished when faced with such assuredness, given I’m a veterinary oncologist and treating cancer is what I do for a living. With time, I’ve come to appreciate such an owner’s motivation for simply seeking my advice without intention to follow it.

Somewhere in the middle lie owners who initially decline therapy, but later change their minds and elect treatment.

Personal Experience Influences Decision

Most animals with cancer are diagnosed at relatively asymptomatic stages of disease. Owners are typically shocked if I tell them their otherwise happy and healthy dog or cat might only be expected to live a few weeks or months following a diagnosis of an aggressive cancer such as lymphoma or high-grade mast cell disease. Convincing that owner to pursue treatment is a challenge, until the pet’s health declines and the owner feels urgency to move forward out of desperation.

More often, owners digest the information I present to them and reverse their initial decision to not treat after learning the facts about chemotherapy. Their prior misconceptions may stem from personal experience with chemotherapy, or from observations of close friends or family members. Even an owner’s primary veterinarian can discourage meeting with an oncologist by perpetuating myths about cancer care in animals.
Of all the misunderstandings related to chemotherapy preventing owners from pursuing treatment, the biggest hurdle I face is communication with owners who are certain chemotherapy is guaranteed to make their pet sick.

Chemotherapy Side Effects and Quality of Life

The goal of veterinary oncology is to preserve quality of life for as long as possible while minimizing potential deleterious effects. Approximately 25% of all animals receiving chemotherapy will experience self-limiting side effects from chemotherapy. This generally entails mild gastrointestinal upset and/or lethargy that occurs during the first several days following treatment, and they only last for a day or so.

Adverse signs can usually be controlled using over the counter or prescription medications. Roughly 5% of chemotherapy patients will have severe side effects that require hospitalization. With appropriate management, the risk of these side effects causing the death is less than 1%.

If a patient experiences serious side effects, the prescribing oncologist will reduce future doses of chemotherapy to avoid similar complications in the future. Additionally, to help reduce the risk of complications in sick pets, every precaution is made to ensure they are strong enough to undergo treatment prior to instituting therapy.

The quality of life for animals receiving chemotherapy is excellent. Multiple studies indicate that the majority of owners are happy with their choice to pursue treatment for their companions and their outcomes and would elect to pursue treatment again if necessary.

Placing Your Trust in Medicine

For those owners who initially decline treatment, but then move ahead, experience tells me they would feel no different from those owners committed from the onset of diagnosis.

If you’re facing a diagnosis of cancer in your pet, you do not need to be absolutely positive you want to pursue treatment prior to speaking with an oncologist about your options. If you’re concerned chemotherapy will be “torture” for your animal, I can assure you this is untrue. No veterinary oncologist endures the rigors associated with their training and credentialing with the goal of imparting pain and suffering on their patients.

Veterinary oncologists are here to make your pet feel better from their disease and to know the appropriate and least impacting treatment for their situation. We’re not here to convince you to treat with chemotherapy. We’re here to provide the facts and allow you to consider what is most appropriate for your companion.

Even if it takes a little time for you to reach your decision, your oncologist will be there for you and your pet during your time of need.

Chemotherapy for Dogs: Everything you need to know!

I recently participated in an interview with a fellow writer for petmd.com on what pet owners need to know about chemotherapy in dogs.  You can find the link to the full text here and a transcription of the article below.

By: Carol McCarthy

“Your dog has cancer” might be the four scariest words a pet parent can hear. After you get that diagnosis, chances are you scarcely hear your vet lay out the treatment options, which likely include chemotherapy. Understanding exactly what this treatment is and how it works, however, will ensure that you make the best decision for your dog. Learn more about what chemotherapy for dogs is, how much it may cost, and what the process will be like for your pet, below.

What is Chemotherapy and Why Would My Dog Need It?

Chemotherapy is a term given to a group of drugs that have the ability to kill cancer cells in dogs. The specific medication or combination will depend on the type of cancer your dog has, as well as his overall health. Your vet will monitor the chemotherapy treatment to ensure that it is working well with minimal side effects. If not, he or she might try another drug or change the dosage and frequency.

Chemotherapy is often prescribed for one of the most common cancers in dogs, lymphoma, as well as for some other malignancies.

“Chemotherapy is recommended for cancers that either have already spread to other areas of the body (metastasized) or are known to have a high potential for metastasis,” said Dr. Lisa Barber, assistant professor of oncology and chemotherapy at Tufts University’s Cummings School of Veterinary Medicine.

Dr. Joanne Intile, staff oncologist at the East End Veterinary Emergency and Specialty Center in Riverhead, N.Y., said that the use of chemotherapy depends on the type of cancer and other factors. “The ultimate recommendation depends on whether it is a single tumor on the skin, whether we can do surgery, if it is more widespread or the dog isn’t a good candidate for surgery,” she said.

If surgery is advised, the doctor will remove the cancerous tumor. The tissue containing the cancerous cells will be sent to a laboratory where a pathologist (a veterinary specialist) will examine the cells under a microscope. The pathologist will look at the edges of the cancerous tissue to determine if they are likely to regrow in that location and will grade the cancer on its likelihood for metastasizing. Cancers considered “high grade,” that is, those that have the likelihood to metastasize, often are treated with chemotherapy, Barber said.
The goal of chemotherapy in animals is different from for humans, which is why treatment is less aggressive. With pets, the primary goal of chemotherapy is to provide your cat or dog with the best quality of life for as long as possible.

“We hope for a cure,” Intile said. “But we don’t see a lot of cures because we don’t treat them as aggressively. Their quality of life is most important. Unlike human oncology, it’s quality-of-life [treatment], not life-at-all-costs [treatment].”

How Much Does Chemotherapy for Dogs Cost?

As with any medical treatment, chemotherapy cost can vary widely depending on the frequency and duration of the treatment, the drug(s) used, the medical facility and geographic location.

“At Tufts, a standard chemotherapy protocol for lymphoma is likely to cost $3,500 to $4,500. At other clinics, the cost can be $10,000 or higher,” Barber said. A commonly referenced standard treatment for this type of cancer is the Madison Wisconsin Protocol, which combines three drugs over a 25-week period of time.

A least expensive option would be an approximately $30 charge per injection, Intile said, with costs rising into the thousands for more comprehensive treatments that require a duration of many months and/or more frequent injections. When describing treatment plans to pet parents, “we never say ‘this is the only way to do it,’” she said. “We always come up with options based on their budget, lifestyle and how often they can come in.”

Barber and Intile said that pet insurance should cover some of the costs of chemotherapy, but it depends on the company and the policy. “For some dogs that are particularly prone to cancer, insurance companies may require a specific cancer rider,” Barber said.

A rider provides an insurance policy holder with additional coverage for a specific illness or situation. Insurance companies typically offer these policy options at an additional cost, which can vary widely.

What Can I Expect During My Dog’s Chemotherapy Treatment?

How chemotherapy is administered depends on the drug given. Intile said most treatments are administered by injection and last just a few seconds (similarly to a vaccination) to a few minutes. Some intravenous drug infusions can take all day but are rarer, she said. Other chemotherapy treatments are given orally, in the office or at home.

Intile allows an hour for a chemotherapy treatment appointment, which includes time for paperwork, bloodwork, an exam and follow-up instructions. These appointments are similar to a typical vet visit, she said, and are designed to minimize stress for both dog and pet parent.

What Are the Side Effects of Chemotherapy in Dogs?

Side effects for dogs are milder and generally last for a shorter period of time than for humans receiving chemotherapy because dogs are given less-aggressive treatment, Intile said. In fact, 75 to 80 percent of dogs have no side effects, she said. When present, typical side effects include loss of appetite, vomiting and diarrhea.

Less than five percent will suffer those effects more severely and will need to be brought into the vet to receive fluids, she said. “There may be little windows of time to restrict activity, maybe days three to five (after treatment). But we don’t want you to put your dog in a bubble. Our goal is for your pet to have a totally normal lifestyle,” she said.

If symptoms do not resolve in a day or two, call your veterinarian.

What causes side effects is the indiscriminate nature of chemotherapy drugs, which kill both normal and abnormal cells in an “innocent bystander” effect, Barber said. Such indiscriminate destruction can affect your dog’s bone marrow, which produces blood cells. “The most common problem that we see is low white blood cell counts. The white blood cells are the first line of defense against infection,” and a low white blood cell count can put dogs at risk for infections, she said.

Unlike people, dogs typically do not go bald from chemotherapy, although they might lose their whiskers, Intile said. Breeds that have hair that grows constantly, such as Poodles, Yorkshire Terriers, Portuguese Water Dogs, can lose some hair, which might grow back in a different color, she said.

How Often Will My Dog Need Chemotherapy?

Frequency of treatments will depend on the type of cancer, the dog’s overall health, the specific drug and family wishes. Most treatments are given in intervals ranging from once a week to once every three weeks, Barber said. That frequency can last a couple of months, followed by every four to six weeks.

The duration of the treatment is also dependent on the type of cancer and can last from a few months to a few years.

“For lymphoma, most standard chemotherapy protocols last between 16 and 24 weeks. However, unless the client wishes to stop, this often is not the end of treatment. Once the initial protocol is completed and the animal is in complete remission (no cancer detected), we give the animals a rest from treatment and wait until we see that the cancer is back. We then start chemotherapy again,” Barber said.

For other types of chemotherapy, particularly when a malignant tumor has been removed and prevention or delay of a reappearance is the goal, a typical course of chemotherapy lasts about three months, she said.

Is it Safe to be Exposed to my Dog’s Chemotherapy Drugs?

The drugs remain active in your dog’s waste for the first few days after treatment, so pet parents are advised to be cautious and to wear gloves when cleaning up after their pet. Intile said her practice provides pet owners with chemo-proof gloves to wear if administering oral drugs and advises them to always wash their hands after administering the drugs and cleaning up, even if wearing gloves.

Women who are pregnant or breastfeeding and those with weakened immune systems, such as the elderly, should be particularly careful around their pet’s waste, she said. However, you do not have to worry about your other pets sharing water bowls, food dishes or utensils with your sick dog, she added.

When storing chemotherapy drugs in your fridge, be sure to keep them in a container within a container away from your own medications. If you do accidentally ingest any of your dog’s medication, call your doctor, not your vet, who by law cannot dispense medical advice to people.

Are There Alternative Treatments for Dogs with Cancer?

Adding to your vet’s cancer arsenal of surgery, radiation and chemotherapy is another option: immunotherapy. This is a type of vaccine that is used to stimulate your dog’s own immune system to attack the cancer. “Right now the main focus for that is in dogs with melanoma (and osteosarcoma),” Intile said.

Some of the larger veterinary university research hospitals are also using bone marrow transplants to treat some cancers, Intile said. To be sure you and your pet have access to the latest treatments and possible clinical trials, consider bringing your dog to a facility that specializes in veterinary oncology.

When the remedy is the poison…

There’s a specific routine we follow for each pet arriving for a chemotherapy appointment. Owners arrive and are greeted by a technician, who will ask several questions about how their pet is doing and if any complications from a previous treatment arose.

If all is “status quo,” the patient will be taken to our treatment area, where their vital parameters (temperature, heart rate, respiratory rate, and body weight) will be recorded and the required blood samples will be drawn and run in our laboratory.

I then perform a full physical exam and make sure there are no contraindications to treatment (i.e., health related reasons to withhold treatment).

The oncology technician will retrieve the lab results, examining the printout for any sign that the blood machines are having a meltdown, and if necessary, make blood smears for me to interpret in conjunction with the automated results.

I review the results, then write out the prescription for the chemotherapy drug, including all associated calculations, determining the amount of drug in both milligrams and millilitres where applicable, and reiterating the route of administration (e.g., intravenous, subcutaneous, orally). Every calculation is then double checked by the technician responsible for administering the dosage.

The patient’s body weight, drug, dosage, and amount, as well as results of their lab-work, are manually entered on their “chemotherapy flowsheet,” a tangible record of all prior treatments.

Current dosages are back-checked to that patient’s previous dosages, where applicable. For example, we cross-reference their current weight to be sure it is within their previous weights, that it was recorded in the correct units (kilograms versus pounds), and that the dose of chemotherapy is similar to what it was at a previous visit.

This painstaking attention to detail may seem ridiculously tedious. Why is the process of administering a medication so involved—especially when that patient has received the same drug numerous times before? What is the point behind the orderly procession of events we prescribe?

The answer lies in what is known as the narrow therapeutic index of chemotherapy drugs.

Therapeutic index refers to a comparison of the amount of a drug necessary to cause a beneficial effect and the amount causing toxicity.

Paracelsus, a 16th century philosopher, stated, “All things are poison and nothing is without poison; only the dose makes a thing not a poison.” This is frequently paraphrased to, “the dose makes the poison” (Latin: sola dosis facit venenum), an excellent summary of the basis of therapeutic index.

Every prescription medication has a therapeutic index. A dose below the lowest margin of this index will result in a lack of effectiveness. A dose above the highest margin can lead to side effects. In the most extreme cases, the side effects can equal death. Dosages within the therapeutic index will be effective for treating the condition in question, but will remain non-toxic for the patient’s healthy cells.

Some prescriptions have a wide therapeutic index, and veterinarians have a good deal of “wiggle room” in what can be dispensed based on a given patient’s size.

For example, the same exact dosage of an antibiotic can be equally therapeutic for a 30lb dog as for a 50lb dog. Similarly, a 50lb dog can be prescribed 2-3 tablets of a particular pain medication to be given every 8-12 hours. The wide therapeutic index of those drugs allows for such variations.

Chemotherapy drugs, on the other hand, have little to no safety margin and a very narrow therapeutic index. This means the dosage of a chemotherapy drug necessary to cause an anti-cancer effect is very similar to that which causes adverse effects.

Therefore a slight error in calculation leading to even a minuscule overdose of drug can lead to catastrophic effects for that patient. In those cases, the patient’s healthy tissues will be exposed to levels of drug that can be at best moderately damaging or permanently affected, and at worst cause a fatal reaction.

We might be able to cure more cancers in pets if we could give them higher dosages of chemotherapy, but we would also bring those animals to the brink of death before any potential success. This is neither an ethically or financially feasible option in veterinary medicine. We also would have a much higher death rate from treatment, losing large numbers of patients to complications from treatment rather than disease.

I’d be remiss if I didn’t acknowledge that at least part of my anxiety about dosing chemotherapy arises from my Type A personality. I’m known for calculating and re-calculating doses several times before giving a thumbs up on the prescription (and even continuing to recheck calculations as the drug is being given). My paranoia stems from knowing all the things that can go wrong when the therapeutic index is breached. However, it’s certainly fueled by a tiny bit of compulsion as well, as I tend to be more obsessive about such details than my colleagues.

With proper and meticulous attention to detail, I’m ensuring that the therapeutic index of chemotherapy drugs I prescribe isn’t breached and errors are avoided.

Although it’s certainly monotonous to perform so many extra steps for every appointment, the process is integral to guaranteeing my patients are treated with the same standard of care I would expect for myself.

A surprising risk of chemotherapy you may never have considered…

During the final year of my residency in medical oncology, I was required to give chemotherapy to my patients with cancer. One case that stands out is a cat I treated with intralesional chemotherapy for a recurrent fibrosarcoma.

As a typical resident, I possessed an inappropriate level of enthusiasm about this task and I asked one of my colleagues to take pictures of me performing the treatment.

In one picture I’m mixing two syringes: One contains sterile sesame oil, which provides a repository for the chemotherapy to remain in the tissue after injection. The other contains carboplatin chemotherapy.

Untitled

Improper mixing of chemotherapy using minimal personal protective equipment and incorrect syringes/adaptors

In the next picture, I’m injecting the sesame oil/chemotherapy mixture into the surgical scar on the cat’s head. The only personal protective equipment I’m wearing in either picture is a pair of nitrile gloves.

I had a healthy respect for the hazards related to chemotherapy, but I primarily focused on those related to side effects. I knew which drugs were vesicants versus irritants (i.e., severe blisters versus annoying rashes), and the deleterious effects they could wreak on bystander organ systems.

What I lacked was an understanding of the risks that unsafe handling of chemotherapy posed to my health. In fact, the bulk of my awareness of chemotherapy safety came following my board certification.

The treatment of cancer in pets is far more popular today than ever before. Yet there is a lack of concurrent education of the risk chemotherapy poses to the healthcare team during its preparation, administration, and cleaning of eliminations.

Studies characterizing the impact of secondary exposure to chemotherapy on human oncology health workers with regard to cancer prevalence, reproductive risks, and acute toxicities show little risk.

However, markers of toxicity and measurable levels of drugs and their metabolites have been found in the urine of healthcare workers exposed to chemotherapy. This occurs in highly trained and experienced individuals working in human medicine, where, unlike working with animals, contact with bodily eliminations (a major source of contamination) is minimal.

Veterinary studies regarding environmental risks from chemotherapy are lacking. We know dogs undergoing chemotherapy treatment for lymphoma and mast cell tumors have measurable levels of vincristine, vinblastine, and doxorubicin—all chemotherapy medications—in their urine at up to 3, 7, and 21 days after administration, respectively. This is a serious consideration for potential exposure.

Pet owners ask a lot of questions about chemotherapy and what to expect as their dog or cat goes through treatment. Surprisingly, I’ve never been asked about what ‘s done to ensure the treatments are done safely and without risk to their animal or to the staff. Either they haven’t considered the consequence of a lack of experience with the treatments or, more likely, they simply assume correct measures will be taken.
Here are some key points related to safe administration of medications that chemotherapy clinics should employ on a regular basis:

Experience is key:
Any technician or doctor giving chemotherapy must be adequately trained in the safe handling and administering of the drugs. Persons administering drugs need to be familiar with their mechanisms of action, correct dosage and route of administration, side effects, and potential routes of exposure.

Use a hood:
A class IIB or III, biological safety cabinet contained in a separate room, with venting to the outside should be used for the preparation of chemotherapeutic drugs, including oral medications. Using the appropriate biosafety hood ensures inadvertent contact does not occur through aerosolization during the preparation of drugs, or in case of accidental spill.

Use a closed, contained system:

Proper use of a commercially available closed contained system for administering chemotherapy

Proper use of a commercially available closed contained system for administering chemotherapy

There are several options for commercially available adaptors for syringes and vials used in the preparation and administration of chemotherapy. These systems reduce the risk of aerosolization of vapors from drug containers to ensure no drug leaks out of the syringe into the air or on the staff or pet’s skin during treatment. These systems do not circumvent the need to use a hood as mentioned above.

Dress for the Job:
Individuals should wear powder-free latex or nitrile gloves along with the appropriate chemotherapy resistant face shields and eye protection, and a closed-front, elastic cuffed, non-permeable, lint-free gown.

Be prepared:
Should a chemotherapy spill occur, commercially available spill kits are recommended, and staff must be trained in the appropriate way to clean bodily fluids from patients and also any surfaces coming into contact with chemotherapy during its preparation and administration.

 

I’ve always sought to deliver the highest standard of care for my patients. Time and experience allowed me to recognize the importance of extending that goal to provide the highest level of safety for my co-workers, owners, and myself. If your pet receives chemotherapy, I would urge you to inquire about the safety measures taken to ensure that those involved in your pet’s treatment are doing the same.

Metronomic chemotherapy – is it the right choice for your pet?

In order for tumor cells to multiple and spread, they must develop their own blood supply through a process called angiogenesis. Angiogenesis inhibitor chemotherapy drugs work to stop or slow down this process, thereby controlling tumor growth. Metronomic chemotherapy is one example of angiogenesis inhibition treatment, which is becoming a popular treatment option for pets with cancer.

 

The definition of metronomic chemotherapy is variable, but usually refers to the continuous administration of low doses of oral chemotherapy drugs designed to target the endothelial cells lining the blood vessels supplying tumor cells.

 

When traditional cytotoxic chemotherapy is administered at maximally tolerated doses (MTD – see previous blog article entitled “Is the remedy for cancer worth the cure?”), death of the endothelial cells lining the blood vessels of tumor cells occurs first, followed by the death of the tumor cells. When we administer chemotherapy in this manner, we typically need to give our patients a rest period between subsequent treatments so healthy cells can repair and regenerate. This delay, necessary to prevent excessive side effects, unfortunately allows damaged tumor blood vessels to recover as well, and may lessen the overall efficacy of the treatment.

 

Metronomic chemotherapy entails the chronic administration of low-dosages of chemotherapy, so theoretically the inhibitory impact on the tumor blood vessel growth is maintained, but the dose is insufficient to cause damage to healthy cells.

 

Historically, metronomic chemotherapy in veterinary medicine consisted of the combination of low doses of oral cyclophosphamide with a non-steroidal anti-inflammatory drug (Feldene/Piroxicam ®), and in some cases, an antibiotic (Doxycycline).

 

Since it’s inception, several other drugs have been examined as metronomic therapy including veterinary approved non-steroidal anti-inflammatory drugs (e.g. Metacam) and other chemotherapeutic drugs (e.g. Lomustine (CeeNu®) and chlorambucil (Leukeran ®))

 

My opinion of metronomic chemotherapy is it’s utilized most effectively in patients where we suspect microscopic cancer cells are present, but at levels where we are unable to detect them. There are two studies I feel are good examples of using metronomic chemotherapy in this exact setting. One looked at dogs with splenic hemangiosarcoma and one looked at dogs with soft tissue sarcomas.

 

Splenic hemangiosarcoma is a very aggressive type of cancer in dogs, and even when the primary tumor is removed via splenectomy and there is no evidence of spread at the time of surgery, most dogs will go on to develop metastases within just a few short weeks to months. Soft tissue sarcomas typically present us with the exact opposite challenge. They are extremely difficult to remove completely with surgery, but usually have a low chance of spread. Though not perfect in their design, in those studies, dogs that underwent treatment with metronomic treatment survived longer and had longer time to tumor regrowth when compared with dogs treated with surgery alone.

 

Metronomic chemotherapy is used to treat a variety of cancers in veterinary patients, other than those listed above. I feel metronomic therapy is most effective in cases where the primary tumor is adequately controlled (e.g. with surgery and/or radiation therapy) and there is no evidence of spread AND that patient has undergone the current standard of care of treatment. For me, the best example would be a dog with appendicular osteosarcoma, which underwent limb amputation and full course injectable cyctotoxic chemotherapy. We know that even with such aggressive treatment, most of those dogs will still go on to develop spread later on and succumb to their disease within 6 months of stopping treatment. I recommend metronomic treatment in those cases. For most cases this will be once injectable chemotherapy is complete, but I am becoming more and more comfortable combining metronomic treatment with injectable chemotherapy.

 

I will also use metronomic chemotherapy in cases where the pet isn’t a good candidate for conventional chemotherapy, or when owners simply can not travel to the hospital to see me as frequently as would be required for other protocols.

 

I’ve used metronomic treatment in cases where visible tumors are detected (e.g. metastases) and the pets are still feeling well. Those are the most challenging cases to treat with chemotherapy, and the major limitation to using metronomic chemotherapy in this setting is once you can detect a tumor, it probably has grown a very decent blood supply of it’s own, and your chance of slowing that down is going to be less (but not impossible). In such cases, owners must be willing to monitor their pets very closely so we can be sure the treatment isn’t causing harm, and to be sure we are truly seeing a benefit from the treatment.

 

A very important aspect of treating cases with metronomic chemotherapy is making sure owners understand this is chronic therapy that requires constant monitoring. Since this form of treatment is relatively new for veterinarians, we don’t really know what adverse effects are possible, so it’s important to watch patients carefully and recognize early signs of drug intolerance before the animals are showing adverse effects. We are usually seeing patients on a monthly basis and performing tests to look for tumor progression and/or spread every few months.

 

Metronomic chemotherapy is a promising new treatment option for veterinary cancer patients and I’m excited to see where research is headed in the future. I enjoy being able to provide owners with cutting edge treatment options, and many owners feel empowered by my ability to expand my own knowledge from information I gain from their pet.

 

In this respect, metronomic treatment certainly brings truth to the statement “Less is more”, as we’ve learned a great deal about how low dose chemotherapy brings a great deal of information on how to control cancer, and in many cases, additional survival time with a great quality of life for our patients.

“Could cat feces help cure cancer?”

My eyes widened as they scanned over the title of the website I’d stumbled across.

After pausing for a few moments to recover my composure and swallow a mild wave of nausea, I rolled my eyes sarcastically and thought ,“Yet another misinterpretation of sound medical research written in the name of Internet propaganda for the sake of promoting Dr. Google.”

Yet, as I continued to read further, I found myself intrigued by the concept behind the scientist’ work. The experiments were (thankfully) not designed to establish cat poop as a cure-all for cancer, but rather on using a common intestinal parasite called Toxoplasma gondii to battle tumor cells.

Toxoplasma gondii (T. gondii) is a relatively simple organism found in the digestive tracts of many mammals. T. gondii can cause toxoplasmosis, a disease that is usually not a life-threatening condition, but can result in flu-like symptoms and malaise. In immunocompromised people or animals, toxoplasmosis can be a much more serious problem, and in very rare cases, can even be fatal.

Infection with T. gondii occurs via 4 main mechanisms:

Ingestion of T. gondii tissue cysts in undercooked meat
Ingestion of material contaminated with T. gondii oocysts
Via a blood transfusion or organ transplant
Transplacental transmission from a pregnant female to her offspring.

T. gondii can infect any mammal, but as in real estate for people and single-celled parasites, it’s all about location, location, location. T. gondii thrives in the intestines of cats and it’s our feline friends who are considered the primary hosts for this creature.

Oocysts, which are the “offspring” of adult T. gondii, are shed in the feces of infected animals, including cats. This is the reason why doctors tell pregnant women to avoid scooping their cat’s litter boxes. If they were to become infected by accidentally ingesting oocysts shed in the waste, they could experience a miscarriage.

So what does this all have to do with cancer?

Regardless of the the cell of origin, cancer exists to some extent because the host’s immune system fails to recognize tumor cells as being “different” from healthy cells. Cancer cells work very hard to evade immune reactions and do this by two main mechanisms – they either work to suppress immune reactions or they work to keep themselves appearing as “normal” as possible.

Conventional anti-cancer treatments such as chemotherapy or radiation therapy work by causing damage to cells in a non-specific manner. These modalities attack both healthy and tumor cells with nearly equal fervor. This leads to issues with toxicity and also greatly limits the doses that can be administered safely.

These latter factors have led to a great interest in developing targeted therapies for treating cancer, including options immunotherapy (for example: http://www.petmd.com/blogs/thedailyvet/jintile/2012/nov/how_dogs_with_oral_melanoma_mouth_cancer_are_treated-29501). Immunotherapy anti-cancer treatments attempt to use the hosts’ own immune system to fight off cancer cells in a specific and controlled manner.

The theory behind using T. gondii as an anti-cancer treatment stems from the it’s ability to elicit a strong immune response within the host, designed to fight off the infection. By infecting people or animals with cancer with the parasite, the hope is the patient’s immune system will more effectively primed to battle tumor cells previously hidden from attack.

Research with T. gondii has shown anti-tumor activity in mice with ovarian carcinoma and melanoma. Tumors were confirmed to reduce in size and mice treated with T. gondii developed potent immune reactions. Perhaps the most exciting data showed the mice with melanoma whose tumors reduced in size following treatment with T. gondii maintained their ability to withstand new tumor development when re-challenged with melanoma cells later on.

The long-term goal for the researchers is to develop an anti-cancer vaccine containing the weakened T. gondii organism. Unlike conventional vaccines, T. gondii will be used as a treatment for cancer, rather than a preventative measure.

I do question the efficacy of the vaccine will be in people and/or animals that have been previously exposed to T. gondii. Up to 1/3rd of humans and many household pets test positive for prior contact with the parasite. I would be concerned those individuals would already have immune systems geared towards fighting off T. gondii, and may actually eradicate it before it enough time has passed to stimulate the immune response necessary to kill tumor cells.

Fortunately, treatment with T. gondii does not involve feces, feline or otherwise. Also reassuring is the strain of T. gondii used in the research is a purified and attenuated (meaning weakened) version of the organism that cannot replicate within the host and should not lead to the development of toxoplasmosis.

As for cat-poop being the cure all, I’ve leave you with my parting advice to make sure to keep gloves on and maintain pristine hygiene when your scoop the litter box. And keep on hugging your feline friends with fervor. You never know when you might need one of them to save your life!

Chemo causes what???

During chemo appointments, I always catch up with owners to find out how things are going since the last time I saw their pet. Since > 75% of our patients won’t have anything happen to them after a treatment, I’m usually just checking in to confirm all is going well.

 

For about 20% of patients, there are mild side effects from chemotherapy – nausea, vomiting, diarrhea, decreased appetite, lethargy, etc. We usually hear about these events prior to a pet’s appointment as most owners keep us up to date (sometimes up to the minute…) about what’s going on at home. We are all very comfortable explaining why they side effects can happen and what can be done to prevent them in the future.

 

Sometimes owner’s observations stump me, and I’m at a total loss to explain what they are witnessing. It seems there are some potential “side effects” from chemotherapy I never learned during my residency. Perhaps some examples would clarify what I mean:

 

Me: “Hi Mr. and Mrs. Smith! So good to see you! I’ve taken a look at Fido and his exam and blood work are both completely normal! The technician said he didn’t have any reaction to his treatment last week. That’s great!”

 

Mrs. Smith: “Yes, we really haven’t noticed any side effects from his treatment, and he still has a ton of energy. So much so that we think, we’ll lately he’s just been extra, I don’t know exactly how to put it, but maybe ‘frisky’ would be the right word?”

 

Mr. Smith: “Frisky? Is that what you’re going to call it?”

 

I notice Mrs. Smith’s cheeks have turned an interesting shade of crimson and her eyes are not making contact with mine anymore.

 

Mrs. Smith: “Well it’s really not a big deal, and we’re really happy with how Fido is doing!”
Mr. Smith: “Not a big deal! It’s not your pants leg he won’t stop latching on to!”

 

After a few stunned moments of silence, suddenly it becomes clear to me a diagnosis of cancer and a course of chemotherapy caused a dramatic rise in Fido’s libido, or at least according to his owners it did. As I certainly never learned about this side effect during my training, I had no response other than “Maybe we should look into finding him a girlfriend?”

 

Another one of my favorite “complaints” came from the owner of a cat diagnosed with lymphoma, who noted with complete seriousness, that her cat “never blinked” since starting treatment.

 

“I can just stare at her and she will start back at me and never blink!” she wailed, thoroughly upset and completely expecting me to explain her observation. I sat speechless. I pictured my own cats and thought, “I seriously cannot think of when I’ve seen any of them blink before! Do cat’s really blink? Did I miss the day in vet school when we learned the appropriate blink rate per minute for a cat?” Nothing I offered would console this owner, and I left the room feeling like a bit of a failure.

 

Ben’s owner once told me he thought his dog was becoming “nostalgic” from chemo treatments. This conjured up images in my head of his beloved Ben sitting at home in a high-backed chair near the fireplace, winsomely peering through photo albums of his “life before diagnosis.”   Would he have a pipe in his mouth and a faraway look in his eyes? It took a full three minutes, and a lot of awkward silence before I somehow realized he meant “lethargic” instead of “nostalgic”, and was able to assure Ben’s owner this was not something life threatening at that time.

 

Many owners note their dog will bark less since starting chemo and equally as many note their dog will bark more. Dogs sleep “harder” and cats “sleep more”. Dogs will “pant more, but only at night” and cats will “yowl more, but only at night” And I’m left wondering how is it owners know what their pet is doing more of at night, when they are not home during the day because they are at work?

 

I don’t mean to downplay owner’s fears for their pets. There are definitely legitimate concerns to watch for while a pet is undergoing treatment and also to watch for signs of disease progression. I also recognize pets are likely to experience some of the more nebulous side effects from treatment, just as people do, but are unable to communicate those to us in a way we can understand.

 

However, I secretly find it just a tiny bit amusing knowing many of the signs they describe are likely because they are simply watching their pets so more closely now that they’ve been diagnosed with cancer. And all the strange and bizarre habits and behaviors they had their entire life are now becoming so much more noticeable and are just part of what makes pets such wonderful parts of our lives.

 

In other words, if you stopped staring at your cat, maybe she would stop staring right back at you and blink once in a while. I know. I’ve tried it myself.

Answers to the top 5 questions from owners of pets with cancer:

1. What caused my pet’s cancer?

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The short answer to this question in many cases is “We don’t know”.  I recognize this is a heated question in veterinary medicine and owners are inundated with theoretical causes of cancer (in people and an animals) in the media, in print, and on the Internet.   In general, the best answer I can give is cancer results from a combination of genetic and environmental factors. Evidence for a genetic cause of cancer in animals is supported by examples of breed predispositions to certain tumor types.  There are also heritable forms of cancers that result from mutations in sperm and egg cells. The majority of genetic alterations leading to cancer to occur because of spontaneous mutations. These mutations may occur as a result of chronic exposure to known cancer-causing substances (e.g. sunlight or chemicals.) Environmental causes of cancer have been established in veterinary patients, but I think it’s very important to recognize  how difficult it is to truly prove causality when it comes to tumor development and environmental factors. Although we often do not know the underlying cause of the cancer, advances in surgical, medical, and radiation oncology allow us the opportunity to provide treatment options for owners and help their pets live longer as a result.

 

2. Will performing an aspirate/biopsy cause the cancer to spread/become more aggressive?

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Though tumor cells can disseminate into the bloodstream during surgical manipulation, the ability of these cells to actually arrest within a distant anatomical site and grow into new tumors is poor, and fortunately, most circulating tumor cells are rapidly destroyed by the host’s immune system.  Pretreatment biopsies are typically recommended in order to obtain a diagnosis prior to making more definitive treatment recommendations.   Exceptions would include cases where the biopsy procedure is associated with a high degree of morbidity (e.g. biopsy of the brain/spinal cord) or when knowing the tumor type would not change the
choice of therapy (e.g. biopsy of a splenic mass or primary lung tumor.)

 

3. Will my pet become sick from chemotherapy?

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The goal of veterinary oncology is to preserve quality of life for as long as possible, while imparting the least amount of adverse effect to the patient. In general, approximately 25% of all animals receiving chemotherapy will experience some sort of side effect. This generally entails what are considered mild and self-limiting gastrointestinal upset and/or lethargy during the first few days after treatment. If side effects should occur, they are usually well controlled using over the counter or prescription medications. Approximately 5% of chemotherapy patients will have severe side effects that require hospitalization. With appropriate management, the risk of these side effects causing the death of a patient is less than 1%. If a patient experiences serious side effects, the dose of chemotherapy is reduced to avoid similar complications in the future.  In general, the quality of life for patients receiving chemotherapy is excellent.  Studies have indicated that the majority owners are happy with their decisions to pursue treatment for their pets and their outcomes and would elect to pursue treatment again, after seeing how well their animals did during therapy.

 

4. Does my pet’s age factor in to his/her ability to withstand treatment with chemotherapy/radiation/surgery?

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Cancer is a disease of older animals, and most of the information available for how pets will respond to treatment, risk of side effect, and outcome are based on studies where the average age of patients is in the geriatric (>10 years) range.  Every precaution is made to be sure that patients are healthy enough to undergo treatment prior to instituting therapy, which is the rationale behind the recommendation to perform baseline staging tests and lab work. These tests will ideally allow us to know everything about a cancer patient from nose to tail before starting treatment, and can help us better predict outcomes, side effects, and even tailor treatment plans.  The age of the patient typically does not factor in nearly as much as their overall health status does.


5. Can my pet be around family members or other animals while undergoing treatment?

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In general, while a pet is receiving chemotherapy, it is considered safe for that animal to interact with all family members.  Depending on the chemotherapy drug(s) that the pet is receiving, there may be certain times after a treatment that the pet would be considered at a higher risk for picking up an infection, so precautions may be necessary during a very specified time period. For oral chemotherapy drugs administered at home, it is important that the capsules or pills are kept out of the reach of children. Individuals who are pregnant, trying to become pregnant, nursing, or considered immunocompromised should not handle chemotherapy drugs.  We recommend owners wear non-powdered latex or nitrile gloves when handling chemotherapy drugs and that the person handling the drugs washes their hands afterwards. It is very important never to split or crush drugs, or open the capsules, as this can increase the risk of exposure.  Metabolites of chemotherapy drugs are present in urine and/or feces for up to 72 hours after an animal has been treated. Dogs should be walked away from public areas during this time period. Gloves should be worn when handling an animal’s feces, litter, vomit, etc.  Hands should be washed thoroughly after handling and potentially contaminated fluids/waste.

This entry is paraphrased from a lecture designed for veterinary students originally written by one of my mentors who probably would rather remain anonymous, but somehow manages to come through in my voice more often than would be expected.