How to Know What the Best Chemotherapy Treatment Is for Your Dog

We know you want to do what’s best for your pet—and what’s best for your family’s situation. Treatments for cancer are certainly not cheap, but we’re going to cover the different chemotherapy protocols and how you can find the best one for you and your pet.

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Why chemotherapy is usually the best option

Chemotherapy treatment is typically the best route for dogs with lymphoma, as it gives them the highest chance of going into remission and provides the longest survival time. Lymphoma usually affects multiple places in the body rather than staying localized, so by putting a treatment in action that requires the medicine to appear throughout the body, the best results are achieved. 

Dogs also react totally differently to chemotherapy than humans do. In veterinary oncology, quality of life is the priority followed by survival. This is different than in people where survival is the top goal. Quality of life is important in animals for multiple reasons including having a shorter lifespan and the inability to speak for themselves. With quality over quantity, dogs are not treated as aggressively with chemotherapy as these protocols haven’t been found to increase response to therapy. As their treatment goes on, they usually only have a few slight side effects. These can include loss of appetite, nausea, etc. 

Your veterinary oncologist will work to make sure your pet experiences as few symptoms as possible. 

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Different protocols 

There are a few different routes that chemotherapy treatment for lymphoma can take, this depends both on the type and the intensity of the cancer. The treatment will depend on what your dog needs because of the type and extent of cancer. Every treatment plan has its own benefits and costs Choosing the best option for you and your pet is a hard decision to make, so we're here to ease some of your confusion and list the different options you could choose. 

Single drug treatments

Lymphoma responds well to treatments that can outsmart the cancer cells’ adaptability. Because the immune system is designed to learn how to beat new threats, it becomes tricky when it is those same immune system cells that become cancerous. It is in their nature to adapt, and once a cancerous cell receives prolonged exposure to any single drug, it quickly learns how to combat it.

Therefore, single-drug treatments are not always the most effective for achieving remission on their own but can do a lot to mitigate symptoms. However, any drugs that can be used alone can also be added to a multi-drug treatment plan by your vet if your dog is not seeing the ideal results. 

Prednisone 

Prednisone is a steroid drug that is commonly given to dogs as an anti-inflammatory medicine, sometimes for allergies or itchiness. The drug has many uses, including helping the immune system combat diseases that cause the system to go out of whack. 

Because Prednisone is able to work with the immune system, it has the ability to also treat lymphoma patients by leading to lymphoma cell death. There are a few downsides in choosing Prednisone as your primary treatment. If this is the first line of defense at an early diagnosis of lymphoma it could inhibit further testing and staging of lymphoma because it starts to treat the disease which often leads to confusing and erroneous test results. Another downside is that it is harder to start a chemotherapy regimen after treatment with Prednisone because prednisone alone can lead to chemotherapy resistance by upregulating the p-glycoprotein pump which then pumps some chemotherapy drugs out of the body too fast before they can have an effect on the lymphoma cells We do not know the exact timeframe dogs have to be one prednisone alone to develop chemotherapy resistance, but it is thought to be a few weeks.¹

But treating with Prednisone alone doesn’t have as strong of response rates as a more involved chemotherapy treatment would. Prednisone can make dogs more comfortable by shrinking lymph nodes and stimulating appetite and energy, but sadly most dogs succumb to their disease within 50 days. Still, this is significantly better than the average survival rate of a Lymphoma patient with no treatment, which is 4-6 weeks. 

A Prednisone treatment can be the most cost-effective because it is just a common steroid drug. Most dogs are on prednisone for the remainder of their life.

Managing lymphoma with a steroid-only treatment is a common option for a lot of pet parents, and while it might not bring your pet into complete remission, it can help mitigate some of their symptoms to give them a better quality of life. You can learn more about how a steroid-only treatment will help your dog’s lymphoma in our blog post here.

Laverdia®-CA1

Laverdia®(verdinexor tablets) is an FDA conditionally approved oral tablet for treating canine lymphoma. It has demonstrated the ability to limit a nuclear cell process that can lead to the complete destruction of a lymphoma cancer cell.

This drug is more targeted and works differently than other more traditional chemotherapy drugs. Laverdia has been found to be effective in treating lymphoma but it is not better than multi-agent injectable chemotherapy. Laverdia is a good option for pet owners who want more than prednisone alone but do not wish to pursue more traditional chemotherapy.

More info on Laverdia. 

Doxorubicin

Doxorubicin is one of the more common single-agent chemotherapy drugs; the nickname for this treatment is Red Devil, but most veterinary oncologist will refer to it as “doxo”. This medicine works well in combination treatment, like CHOP as it is the H drug in this acronym (hydroxydaunorubicin) and the other drugs (Cyclophosphamide, Oncovin (vincristine), and Prednisone), but it can also be seen as a standalone medicine when a single-agent chemotherapy protocol is chosen—either for less frequent treatment interval, cost efficiency or because it is the best option for that particular case. 

Doxorubicin as a single-agent treatment is effective in treating B-cell lymphoma, though it is significantly more likely to bring a dog into remission if combined with other chemotherapy drugs during treatment. The likelihood of remission in a single agent doxorubicin treatment is 74-88% and remission can last anywhere between 4-6 months. 

When using a doxorubicin treatment, it’s usually given once every 2-3 weeks for a total of 5 treatments.⁵ While treatment with single-agent chemotherapy is naturally going to be less costly, be sure to consider if the difference in remission time is worth the cost to you.

More info on Doxorubicin.

Leukeran® (chlorambucil) 

Chlorambucil, also known as Leukeran®, is a chemotherapy drug that interferes with the growth and spread of cancer cells in the body by adding alkylate groups to nucleic acids, distrupts DNA strands, and limits cell division. It is commonly prescribed to pets with indolent lymphoma and chronic leukemia. It is not very effective for high-grade lymphoma, but can be a substitute for cyclophosphamide in the CHOP protocols for dogs who do not tolerate that drug.

Chlorambucil is administered typically as a tablet and is given on an empty stomach and ismetabolized by the liver. The dosage schedule depends on the other drugs your pet may be taking, the type of cancer being treated, and a dog’s response to the drug. The dosage to be given is also reliant on several factors, including the dog’s size and general health. 

More info on Chlorambucil. 

L-asparaginase

L-asparaginase, also often referred to as Elspar, is an enzyme that is used as a chemotherapy drug. This enzyme is used as an antitumor agent because it speeds up the breakdown of L-asparagine, a nutrient that cancer cells basically feed off. Adding Elspar to a cancer treatment helps by removing the fuel source for the cancer cells, which effectively starves them so that the cells can’t reproduce at a rate that would advance the cancer.

Not all healthy cells can rely on their own production of L-asparagine, so it is important for your vet to pay attention to your dog’s intestine, bone marrow, liver, and pancreas if your dog experiences any of the side effects associated with trouble in those areas.

More info on L-asparagnaise.

Tanovea® (rabacfosadine)

Tanovea® is a promising new anticancer chemotherapy drug designed to treat canine lymphoma. While most cancer treatments are initially targeted for human use and then secondarily modified for animals, Tanovea® was developed specifically for dogs, heralding a new era in veterinary research and drug discovery.

The active ingredient of Tanovea® is a compound that quickly mixes in with lymphoid tissues, especially rapidly dividing lymphoma cells. Once inside the cell, this medication inhibits DNA synthesis, interrupts cell division, and induces cell death. 

Clinical studies demonstrated that 73-87% of dogs with lymphoma responded positively to Tanovea® whether they were new to treatment (naive) or had stopped responding to conventional chemotherapy (drug-resistant).

More info on Tanovea®.

Mustargen® (mechlorethamine)

Mechlorethamine is an alkylating agent which is prescribed as a chemotherapeutic drug known as Mustargen®. It binds to the DNA of a cancer cell and prevents it from duplicating prior to cell division. This works to treat cancer because cancer cells usually divide faster and with less DNA error correction during replication than healthy cells do. Because of that, a cancer cell’s DNA is more sensitive to inhibition and cell death. 

The start of the investigation of this particular chemical compound was inspired by the effects of nitrogen mustard, a derivative of mustard gas which was used in chemical warfare during World War I. Being exposed to nitrogen mustard was shown to have an effect on bone marrow and white blood cells, and from this observation, scientists were quick to connect its possible use as a cancer treatment.

This medication combats cancers that originate in white blood cells. Sometimes it is administered as palliative chemotherapy to reduce malignant effusion, which results in fluid accumulation around the heart or lungs. Lately, it has found use as a lotion for treating skin lesions of cutaneous T-cell lymphoma, and mycosis fungoides, which is a cancer of the immune system.

More info on Mechlorethamine.

Mitoxantrone

Mitoxantrone is a synthetic drug classified as an antitumor antibiotic that is used to halt cancer growth. It’s similar in structure to doxorubicin but does not have the same cardiotoxic side effect. It works by disrupting the DNA synthesis and repair by inserting itself between the DNA bases and blocking the enzymes that make the two DNA strands. Cancerous tumors are characterized by an out-of-control, rapid cell division and are unable to stop dividing when they contact other like cells. This drug blocks them from contacting other cells and interferes with DNA functions during multiple phases of the cell cycle and is cytotoxic to both rapidly dividing healthy and non-healthy cells. Similar to many chemotherapeutic agents, cells dividing rapidly are more likely to be destroyed. Unfortunately, rapidly dividing cells such as blood cells and cells lining the gastrointestinal tract and hair follicles are also adversely affected affected similar to other chemotherapy drugs.

More info on Mitoxantrone.

Vincristine

Vincristine is used to treat various types of cancer. It is a cancer chemotherapy drug that is often used with other chemotherapy drugs to slow or stop cancer cell growth. The job of chemotherapy is to kill cancer cells, including those that may have spread beyond the main tumor.

Vincristine comes as a liquid solution and is given through an IV push or infusion. It is a vesicant, which is a chemical that can cause extensive tissue damage and blistering if it escapes from the vein. Vincristine can have some dangerous side effects if not given correctly so your vet will have to be carefully trained to administer this drug. Afterward, you’ll have to keep an eye on the location of the IV site. Should there be any pain, discomfort, swelling, or redness at the site, alert your healthcare provider immediately. Vincristine is often used to treat cancers like Leukemia, lymphomas, sarcomas, and tumors in the bones and lungs. Typically, treatment is given once a week for as long as your dog’s oncologist deems required, a timeline that is generally based on how well your dog’s body responds to the treatment. Vincristine is part of the CHOP protocol and is not often used as single-agent treatment for lymphoma

More info on Vincristine.

CCNU (Lomustine)

Another commonly used single-agent chemotherapy medicine, as well as one that works great in combination treatments, is CCNU. CCNU, also called Lomustine, is an alkalizing agent designed to cause trouble to the dog’s DNA and RNA, stopping them from transcription and replication respectively leading to tumor cell death CCNU can affect the liver so many dogs are put on the liver supplements to help combat this.

CCNU is a common medicine chosen to combat initial cases of T-cell lymphoma. It is also one of the go-tos of rescue protocols to give at the beginning of relapse because it is so commonly effective.

CCNU is helpful for treating cutaneous lymphoma specifically, having roughly an 80-90% response rate in dogs that use it as part of their treatment protocol, with 26% of pets getting to complete remission.⁶

More info on CCNU/Lomustine.

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Multi-agent Treatments 

Prednisolone + chlorambucil 

Prednisolone is similar to Prednisone in more than just spelling. They are effectively doing the same thing with the difference of one step within the body. When Prednisone is given to the patient, their liver works to process the medicine and turn it into Prednisolone. By giving your pet Prednisolone to begin with, you cut out that middle step within the body's process.⁴ Prednisolone is often given to cats but rarely dogs.

Chlorambucil is an alkylating drug described above.³ 

When these two drugs are partnered together they are effective in treating low-grade T-zone cell lymphoma. They work together to provide two different attacks on the cancerous cells and create a stronger chance for remission. 

CHOP

For many vets treating lymphoma, this protocol is considered the “Gold Standard”—the one that they know will most likely have the best response and remission times. It’s the best for treating multicentric lymphoma, which is the most commonly found form. 

CHOP consists of 4 different chemotherapy drugs. Cyclophosphamide, Doxorubicin Hydrochloride (sometimes called Hydroxydaunomycin), Vincristine sulfate (brand name Oncovin), and Prednisone. Each of those different drugs works to attack cancer cells in a different way. 

The CHOP protocol is effective for the initial treatment of multicentric, B- or T-cell lymphoma.

This treatment typically goes over the course of 15-19 weeks, or up to 25 weeks. Your dog will be alternated between the medicines so that the cancer cells don’t develop a resistance to any of the drugs.⁷ 

The CHOP protocol is one of the most commonly used treatment plans for dogs with lymphoma; you can learn more about how the CHOP protocol works and how much it can cost in our blog post here. 

L-CHOP

Although CHOP is already a very strong protocol, in certain situations it can make sense to add to it. L-CHOP is a protocol that follows the same pattern as CHOP with the addition of L-asparaginase—which is given as an injection.

The addition of L-asparaginase is often used in sick lymphoma pets and animals with leukemia. It is also used as a rescue chemotherapy drug.⁸

This is added towards the beginning of a CHOP protocol and typically lasts the same number of weeks, between 15-17.

COP

COP protocol is similar to the CHOP protocol in that they both feature a multiagent chemotherapy treatment and most of the same drugs, with the exception of Doxorubicin. This particular protocol has treatments that are more spread out than the CHOP protocol which can be more convenient for many pet owners. Also, this is a good option for pets who cannot receive doxorubicin because of their heart. 

The COP protocol is more beneficial for the treatment of B-cell lymphoma types. When the COP treatment is given to B-cell lymphoma patients they are expected to be in treatment for up to 12 months and many achieve a remission time of around 6-9 months on average.¹⁰ 

While the COP protocol is slightly cheaper than CHOP, the remission length and rates reflect the difference on average.

LOPP

LOPP is a high-grade T-cell lymphoma equivalent of the CHOP protocol. It has a few of the same drugs: vincristine (O), and Prednisolone (P). LOPP runs on a similar multi-agent process that CHOP protocol is known for and targets the harder-to-treat high-grade T-cell lymphoma. 

LOPP treatment uses Lomustine (CCNU), Vincristine, Prednisolone, and Procarbazine. This is one of the most effective treatments for T-cell lymphomas, a cancer that otherwise is difficult to treat.

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Relapse treatments 

When a dog’s remission ends they often have to go into a new treatment plan, although there are times when a repeat of the same system that got them into their remission is safe to reuse. A patient who participated in the CHOP protocol to get into their first remission, for example, would be a good candidate to restart the CHOP treatment if they relapsed after a minimum of two months after finishing CHOP. In this instance, the chance of them achieving a second remission with the same treatment plan is very possible.

For other dogs, there are a few options that can extend their life through a second remission. 

MOPP

The MOPP protocol is one of the more common multi-agent chemotherapy treatments given in the case of a relapse as a rescue protocol. It consists of a combination of two injectable drugs and two oral drugs similar to LOPP. The combination of chemotherapy drugs for this protocol consists of Mustargen, Vincristine, Prednisone, and Procarbazine. Mustargen and Vincristine are injectable drugs that are given on day one of the process and repeated again after 7 days. Prednisone and Procarbazine are given orally at home on day one and given regularly for 14 days. After that cycle of 14 days is completed, there is a 7-day rest period. 

When this program is put into action the 3-week cycles are repeated as necessary; in an effort to achieve complete remission, it takes around 6-8 cycles. This totals out to about 4.5-6 months of active treatment time.¹¹ In the case of a relapse the chances of achieving a second complete remission is about 31% and it can last an average of 2 months which means most dogs do not finish the full protocol.¹² 

Dacarbazine + DOX(B-cell) or + CCNU (T-cell) 

Dacarbazine was originally used in treating human Lymphoma cases. After identifying its usefulness in treating canine lymphoma and verifying that it was completely safe to use on dogs, it was found to be more beneficial to lingering cases. 

Dacarbazine, or DTIC in short form, has been discovered to be one of the best medicines to use in a rescue protocol because it is not commonly used in the initial multidrug treatment. This newness is useful to rescue protocols because the cancer cells have usually developed resistance to the old drugs, rendering them practically useless.

By pairing this medicine with either Doxorubicin or CCNU, the treatment plan can target B-cell and T-cell lymphomas more directly and effectively.¹³ 

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How the MDR1 gene affects lymphoma treatment

Chemotherapy treatment for dogs is generally one of the best ways to achieve remission from canine lymphoma, but some dogs are not able to be given the same treatment as others. There’s a genetic mutation called the MDR1 (ABCB1) gene that affects a dog’s body’s ability to process drugs. This gene is common in herding breeds with white feet.

If a dog with the MDR1 genetic mutation is treated without consideration for the gene, there are several dangerous side effects that may arise because some drugs are not able to be removed from the body like normal leading to increase side effects from certain medications. If you have a dog that could potentially fall into the herding dog category it is very important to test them for this gene before starting a treatment plan. If your dog has the MDR1 gene mutatation, their options of chemotherapy drugs are more limited, but knowing this information will allow you to make a more informed decision in your pet’s care and will prevent your dog from undergoing any treatments that are guaranteed to fail. 

You can learn more about the MDR1 gene in our blog here. And you can learn about getting your dog tested for the gene here. 

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Personalized Prediction Profile

ImpriMed has developed their lab to go further than just identifying the type of lymphoma that your pet has. Our systems have the added option of our Personalized Prediction Profile, which includes a CHOP response prediction. 

We provide a personalized prediction profile that shows how the treatment will impact your dog, as well as their predicted time frame of relapse.

This prediction allows us to inform both you and your vet what the best route of action would be, as well as what the outcomes are likely to be based on cellular response to our tests combined with artificial intelligence. 

Ask your doctor if they offer ImpriMed’s Personalized Prediction Profile or find an oncologist near you that is already involved.

Learn how to get your vet involved with our program.