After Cancer Remission, Using Chemotherapy to Prevent Recurrence

By Patrick Mahaney, VMD, CVA, CVJ on Nov. 6, 2015

Now that Cardiff has fully healed from the surgeries to remove his small intestinal tumor and nine skin masses, it's time to pursue the plan for chemotherapy. This is not the first time Cardiff has undergone chemotherapy, as his first course involved seven months of University of Wisconson-Madison Canine Lymphoma Protocol (aka CHOP), ending in July 2014.

Part of me is conflicted about giving him chemotherapy again, as he’s essentially in remission now that his cancer has been surgically removed from his body and no other detectable traces can be found. Yet, I want to give him the greatest chance of having a good quality of life that is longer than a few months, and cancer cells could still be lurking in his body that will become new tumors over the coming weeks to months (see Microscopic vs Macroscopic Disease — What is the Difference?). Additionally, Cardiff tolerated his chemotherapy so well last time that I’m hopeful he will do so again.

I’m fortunate to have Cardiff’s chemotherapy plan overseen by the Veterinary Cancer Group’s Avenelle Turner DVM, Diplomate ACVIM (Oncology), as I’m not experienced enough in the realm of chemotherapeutics to govern the process myself.

Cardiff’s upcoming protocol will involve four drugs given concurrently or individually over an eight week re-induction course. The drugs are known by the acronym CHOP, which stands for:

Cyclophosphamide (brand name Cytoxan)

As an alkylating agent, the effects of Cyclophosphamide are to bind to cellular DNA to prevent cell division and cause cell death. Unfortunately, Cyclophosphamide is not specific for cancer cells, so normal cells can be affected and killed in the process of achieving an anti-cancer effect. Rapidly dividing cells are those that are the most susceptible, so normal cells lining the intestines, composing bone marrow, and allowing for reproduction are commonly affected along with the cancer cells.

Digestive tract signs (decreased appetite, vomiting, and diarrhea) and bone marrow suppression are common side effects of Cyclophosphamide administration. As Cardiff has been neutered, there’s no fear of lowering his sperm count by treating him with Cyclophosphamide or other chemotherapeutics.

Hydroxydaunorubicin (brand name Doxorubicin or Adriamycin)

Hydroxydaunorubicin is actually an antibiotic produced by the bacterium Streptomyces peucetius, which has anti-cancer properties. Like Cyclophosphamide, Hydroxydaunorubicin also kills rapidly dividing cells and has similar side effects. Yet, Hydroxydaunorubicin is cardiotoxic, so it damages heart cells and can induce or worsen cardiac diseases. Each successive dose of Hydroxydaunorubicin increases the likelihood of cardiotoxicity, so the more times Cardiff receives it the more closely his heart function will need to be evaluated via ECG (electrocardiogram) and echocardiogram (cardiac ultrasound).

Hydroxydaunorubicin has been nicknamed the “red devil,” as it’s one of the chemotherapy drugs most-likely to induce undesirable side effects.

Oncovin (drug name Vincristine Sulfate)

Like Cyclophosphamide, Oncovin is an alkylating agent that damages cell DNA and also interferes with the production of certain amino acids. It also has side effects similar to Cyclophosphamide.

Prednisone

Prednisone is a corticosteroid prescribed to many pets for a variety of health conditions, with the primary effects being anti-inflammatory to help with allergic conditions.

Depending on the dose prescribed, Prednisone can have an anti-neoplastic/cytotoxic (anti-cancer/cell-killing), immunosuppressive, or anti-inflammatory effect. Higher doses are anti-neoplastic/cytotoxic, mid-range doses are immunosuppressive, and the lowest doses are anti-inflammatory. Common Prednisone side effects will actually be beneficial in Cardiff’s case, as he’ll be more motivated to eat and drink even if he’s feeling digestively upset from his chemotherapy. Less-desirable side effects include increased urination and respiratory rate.

Each week during the re-induction, Cardiff will receive Cyclophosphamide, Hydroxydaunorubicin, or Oncovin, either as an injection or oral administration.

Hydroxydaunorubicin and Oncovin are given as in intravenous injection and Cyclophosphamide is orally administrated. Prednisone will be dosed concurrently over the first few weeks of treatment in a tapering dose and frequency.

With injectable drugs, there’s concern for extravasation, which is where the drug gets out of the vein and causes damage to adjacent tissues. We faced this issue with Oncovin during Cardiff’s last course of chemotherapy, but fortunately it readily resolved with supportive care (see Unexpected Side Effects of Chemotherapy Treatment). With oral drugs, there’s potential for the stomach or intestines to be irritated and digestive tract signs to occur.

Fortunately, Cyclophosphamide and Oncovin are known to have the effect of immunosuppression for diseases like Immune Mediated Hemolytic Anemia (IMHA), which Cardiff has endured four times in his ten years of life. At his last IMHA occurrence in October 2014, Cardiff completed his chemotherapy course three months prior but was not put back on Azathioprine (Imuran) as it was unclear to me and Cardiff’s team of veterinary internal medicine specialists and oncologists whether doing so was necessary.

Azathioprine is the immunosuppressive drug that had been successfully keeping him from developing another IMHA episode without causing detectable side effects. During the first course of CHOP, Azathioprine was discontinued as there wasn’t a perceived benefit in further immunosuppressing him in addition to CHOP. Cardiff didn’t have another IMHA occurrence during the CHOP course, but once CHOP was done his immune system apparently had other plans and he again started destroying his red blood cells (see What Does a Veterinarian Do When a Pet With a Complicated Medical History Gets Sick Again?).

If Cardiff is still in remission after the eight week re-induction period, then his treatments will be given every 14 days for six months. If he’s still in remission after six months, then the treatments will be given 30 days on an indefinite basis.

This course of chemotherapy will also involve a new treatment called T-cell monoclonal antibody (MAb). It’s an immunotherapy agent having a different mode of action from CHOP drugs and will be the topic of my next post.

So, wish us luck in starting chemotherapy again and stay tuned for the latest update.

Has your pet ever undergone chemotherapy for cancer or other ailments? Feel free to share your experience, good or bad, in the comments section.