Managing chemotherapy adverse effects

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When treating patients with chemotherapy in your practice or referring to an oncologist, you may get questions from your clients regarding chemotherapy adverse effects (AEs). Most are mild to moderate, with rare patients (<5%) experiencing serious AEs.

The most common AE is gastrointestinal (GI) upset including loss of appetite, vomiting, and diarrhea. For injectable chemotherapy, this tends to occur 2 to 5 days after treatment. Most patients can be treated on an outpatient basis with antinausea medications such as maropitant citrate (Cerenia) or ondansetron. Metoclopramide can be used as well and is of particular benefit for vincristine-induced ileus in dogs. Crofelemer delayed-release tablets (Canalevia) area new drug specifically for chemotherapy-induced diarrhea that modulates hypersecretion of chloride and normalizes fluid influx into the intestinal lumen. Metronidazole, probiotics, and clay supplements also can be used for diarrhea. Hospitalization is recommended for pets experiencing severe GI upset.

The second most common AE of chemotherapy is myelosuppression, particularly neutropenia. Most injectable chemotherapy drugs cause the neutrophil count to be lowest around 7 days after chemotherapy. Some drugs such as carboplatin, dacarbazine, and lomustine in cats can cause delayed neutropenia 2 or more weeks after treatment. In dogs, a neutrophil count of less than 1000 is associated with a significantly increased risk of sepsis. Most oncologists will prescribe antibiotics in a well, afebrile, neutropenic patient with a neutrophil count below 1000 to 1500. Cats are less likely to develop sepsis even in the presence of neutropenia, and antibiotics are typically prescribed only for cats with a neutrophil count below 500 to 1000.

For patients presenting with febrile neutropenia (sepsis) or signs of sepsis in the absence of a fever, aggressive treatment is needed. These pets should be hospitalized with IV fluids and broad-spectrum antibiotics (such as ampicillin/sulbactam [Unasyn] and enrofloxacin). If available, filgrastim (Neupogen) can be used to try to speed white blood cell recovery and shorten hospitalization. However, once pets are neutropenic, the benefit is limited. Neupogen is most effective when given prior to the development of neutropenia (ideally, started 24 hours after chemotherapy) to prevent neutropenia in pets at risk for sepsis, such as those diagnosed with serious infections after chemotherapy was administered. Neupogen should not be given sooner than 24 hours post chemotherapy, as this can potentiate stem cell death from the chemotherapy and worsen cytopenias instead of improving them.

Some chemotherapy drugs have unique AEs that should be discussed with clients. Examples include the following.

Doxorubicin

Doxorubicin (Adriamycin) can cause damage to the heart and dilated cardiomyopathy. In pets with normal heart function, a cumulative lifetime dose of less than 180 mg/m² (typically, 6 treatments) is generally well tolerated. A screening echocardiogram is recommended in all large-breed dogs and should be strongly encouraged for dogs at high risk of dilated cardiomyopathy, such as Dobermans, or large-breed dogs with a heart murmur or abnormalities on electrocardiogram. Doxorubicin can cause severe nonhealing wounds if extravasation occurs. To help lower the risk of extravasation, pets should be restrained thorough the entire doxorubicin treatment and the drug should be given only by staff experienced in doing so. It is strongly recommended to have the antidote for extravasation, Dexrazoxane (Zinecard) on site any time doxorubicin is being administered; the sooner it is given, the more effective it is. Efficacy is poor 24 hours post extravasation.

Cyclophosphamide

Cyclophosphamide (Cytoxan) can cause sterile hemorrhagic cystitis, or irritation of the bladder. Symptoms of this resemble a urinary tract infection with stranguria, hematuria, pollakiuria, and discomfort. This has been reported in dogs only, although it theoretically could occur in cats as well. Irritation of the bladder occurs due to excretion of a metabolite called acrolein into the urine. The risk for hemorrhagic cystitis can be minimized by using furosemide (Lasix) to encourage dogs to drink and urinate more, as well as taking pets out to urinate every few hours for the first 24 hours post treatment. Clients should be advised to discontinue the drug immediately should lower urinary tract signs occur. If there is no sign of an infection or another cause of the urinary signs and sterile hemorrhagic cystitis is suspected, the drug should be permanently discontinued.

L-asparaginase

L-asparaginase (Elspar) is an induction agent for the treatment of lymphoma and leukemia. It is typically used to try rapidly inducing remission in pets ill from lymphoma or leukemia. AEs are very different than for other chemotherapy drugs. L-asparaginase can cause allergic reactions, with increased risk the more doses a pet has received. Additionally, L-asparaginase can be so effective that it results in rapid cancer cell death, which can occasionally trigger tumor lysis syndrome. Tumor lysis syndrome typically presents in the first 24 to 48 hours after L-asparaginase administration and can have life-threatening or fatal consequences. Pets with tumor lysis syndrome will demonstrate profound illness shortly after treatment and will have characteristic lab work abnormalities including hyperkalemia, hypocalcemia, and hyperphosphatemia and may present with acute kidney injury and coagulopathies. Treatment for tumor lysis syndrome involves treatment of electrolyte abnormalities, coagulopathies if present, and supportive care.

Lomustine

CeeNU (Lomustine) is hepatotoxic, with liver damage more common in dogs than in cats. Denamarin (S adenosylmethionine and silybin) may help lower the risk of hepatic toxicity. Most dogs with lomustine-induced hepatic toxicity will present with asymptomatic elevation in the alanine aminotransferase (ALT) value on a chemistry panel. If the ALT is more than twice the pet’s baseline, it is recommended to discontinue lomustine and consult an oncologist for guidance. Under an oncologist’s care, lomustine may be continued until more significant ALT elevations are seen depending on the pet’s medical conditions and other options available for treatment.

Rabacfosadine

Rabacfosadine (Tanovea) is a newer chemotherapy drug primarily used for the treatment of lymphoma, with effectiveness for B-cell lymphoma. Rabacfosadine has been reported to cause fatal pulmonary fibrosis in a small percentage of patients. Although this AE is rare, there is often no warning on examination or thoracic radiographs until a pet presents in respiratory distress. Once respiratory distress occurs, treatment options are limited. Despite the risk of pulmonary fibrosis, rabacfosadine is an important tool for treating lymphoma and should not be avoided solely for this reason in pets with limited treatment alternatives. Rabacfosadine has been reported to cause skin reactions that resemble severe superficial pyoderma. Skin reactions typically improve with use of steroids, a treatment delay, and dose reduction or discontinuation of chemotherapy.

Understanding and discussing these potential AEs with clients is crucial for informed decision-making and ensuring the well-being of pets undergoing chemotherapy. Open communication and collaboration between veterinarians, pet owners, and oncologists play a pivotal role in achieving successful outcomes and maintaining the quality of life for pets battling cancer.

Valerie Wiles, DVM, DACVIM, joined Veterinary Cancer Group of San Fernando Valley, a Thrive Pet Healthcare partner, in 2015. A Southern California native, Wiles earned her undergraduate and doctor of veterinary medicine degrees from the University of California, Davis. Her passion for oncology ignited during a rotating internship in Sacramento and then traveled to the East Coast, where she completed an internship and residency in medical oncology at Animal Medical Center in New York, New York. In 2015, Wiles achieved board certification in oncology from the American College of Veterinary Internal Medicine. She has served as president of the Southern California Veterinary Medical Association’s San Fernando Valley Chapter, coordinating monthly educational meetings for local veterinarians. Wiles is dedicated to ensuring a high quality of life for her patients, reflecting her strong belief in compassionate veterinary care.