Top tips for managing cancer patients in your practice
DENVER, CO – Cancer is the leading cause of death in pets, but with improved treatments, many cancer patients are living longer and living well. In many cases cancer can be considered a chronic condition that may require chronic therapy, explained Sue Ettinger, DVM, DACVIM (Oncology), speaking at the American College of Veterinary Internal Medicine Forum.
Chemotherapy
Conventional chemotherapy
Conventional chemotherapy is typically given at high dosages, or maximum tolerated dose (MTD). The goal is to kill the rapidly dividing cancer cells. But some normal cells can be temporarily damaged by MTD chemotherapy. As a result there is a break period to allow these cell populations to recover. MTD is typically given weekly to every 3 weeks.
Chemotherapy drugs attack rapidly dividing cells. The normal tissues that are typically most sensitive to chemotherapy are the bone marrow, hair follicles (alopecia), and the GI lining.
Bone marrow suppression most commonly results in a neutropenia, but cats seem to be more tolerant than dogs. Neutrophils and platelets are at greatest risk due to the shorter circulating lifespan, and shorter bone marrow transit times. Neutropenia is the dose-limiting toxicity in veterinary oncology.
Dr. Ettinger said that when she gives a potentially myelosuppressive drug, she likes to check the expected nadir (low neutrophil count), which typically occurs 7 days after chemotherapy administration, to see if antibiotics and/or a dose reduction are needed. She stressed the importance of paying attention to the neutrophil count, not the total white blood cell count. For some chemotherapy drugs the nadir is more variable or later than 7 days, so knowing when to expect the nadir is important.
Alopecia (hair loss) is due to damaging the rapidly dividing hair follicle. The good news is that hair and whiskers will re-grow once the treatments have been completed. She noted that pet owners should be advised about the whiskers and coat so that they are not surprised, but she reminds owners that alopecia is cosmetic and does not affect the pet’s quality of life.
Gastrointestinal (GI) toxicity includes vomiting, diarrhea, decreased appetite, and nausea. It typically begins 1 to 5 days after chemotherapy and is self-limiting, lasting on average 2-3 days. These side effects are less common in feline chemotherapy patients than in dogs.
How toxic is chemotherapy?
The overall toxicity rate is very low in veterinary chemotherapy patients. Dr. Ettinger said that in her experience only 15-20% experience side effects, which are usually mild and medically manageable, and this is even less common in cats than dogs. The primary goal is to provide the best quality of life possible for as long as possible. She added that she will typically add prophylactic medications to prevent side effects like nausea, vomiting, or diarrhea, as necessary.
When a chemotherapy drug is used that is known to have a high potential for bone marrow suppression, such as doxorubicin or carboplatin, a complete blood count (CBC) is often checked after the treatment to see if the neutrophils are low. Antibiotics may be prescribed as a preventive measure. Subsequent doses of chemotherapy are adjusted based on the results of the CBC.
Dr. Ettinger said that in her experience, there is less than a 5% chance that a patient will need hospitalization due to chemotherapy-related side effects. If this does occur, patients are usually hospitalized for typically 24-48 hours with supportive care including IV fluids and antibiotics. Most chemotherapy patients can successfully receive that drug again with a dose reduction.
Metronomic chemotherapy
In contrast to MTD chemotherapy, metronomic chemotherapy is pulse or low-dose chemotherapy given on a continuous treatment schedule. Since it is given daily or every other day, the chemotherapy is given at lower doses then typical chemotherapy, often with reduced toxicity profile.
Instead of killing the cancer cells directly, metronomic chemotherapy targets endothelial cells that line the tumour blood vessels and inhibits tumour blood vessels growth, called angiogenesis. So you will hear that this type of chemotherapy is “anti-angiogenic”. Tumour blood vessel cells are more active than normal blood vessel cells and are the targets of this type of low dose oral chemotherapy.
There is also evidence that some low dose chemo drugs like cyclophosphamide have effect on tumour immunology. It alters a subset of immune system cells in the T-lymphocyte family (regulatory T-cells).
The goal of metronomic chemotherapy is to stabilize the tumour to prevent further growth and spread. There is still much to be learned regarding the best drugs, dose, schedule, tumour types, and toxicity. This type of chemotherapy can be considered for some dogs and cats with advanced metastatic disease.
What to do at the nadir visit?
In addition to running a CBC, it is important to get a good history, TPR, and a complete physical examination. Dr. Ettinger said that she is always interested to know how the patient has handled chemo. For example, did she eat well, was there any vomiting/diarrhea, did the owner use any nausea or diarrheal medications? For the exam, it is important to determine if the pet lost weight or was febrile. She stressed that the nadir CBC should not be an appointment with the technician just to get a blood sample, but also an opportunity to collect the pet’s history and conduct a physical exam, including a temperature.
She recommends antibiotics for patients with a neutrophil count less than 1500. If the patient has a neutrophil count of less than 1500 and is afebrile and feeling well, she recommends managing it as an outpatient. However, if that patient is febrile and sick, it should be admitted for supportive care.
She also likes to collect blood samples from the jugular veins for patients getting IV chemotherapy (unless thrombocytopenic), saving the peripheral veins for treatment. She stressed the importance of avoiding repeating unnecessary blood work in order to keep the interventions and costs down.
Sepsis
Sepsis in chemotherapy patients is typically due to the patient’s own flora. Predisposing factors include neutropenia, cellular immune dysfunction, humoral immune dysfunction, prolonged hospitalizations, indwelling catheters, and poor nutrition.
Dr. Ettinger stressed the fact that the febrile neutropenic patient is an oncologic emergency! In addition, the patient may have an inability to mount an inflammatory response, so the lack of fever, pyuria, or radiographic changes of pneumonia does not rule out sepsis. Signs of illness are unrelated to absolute neutrophil count, but are related to an increased susceptibility to local and systemic infections when neutropenic.
The sepsis work up includes a CBC, chemistry panel, and UA & UCS (if >50,000 platelets). If respiratory signs are present, chest radiographs are recommended, TTW should be considered, and blood cultures may be needed. Catheters should be cultured to rule them out as the infection source.
Treatment includes IVF and broad-spectrum IV antibiotics. Neupogen, the human recombinant G-CSF, stimulates the neutrophil count, but Dr. Ettinger said it is rarely needed, as most patients will rebound on their own.
Chemotherapy should be given at MTD and the shortest possible interval; small dose changes can have significant impact on cancer control. Dose reductions as small as 20% can decrease drug efficacy up to 50%, so she recommends that dose reductions be carefully considered.
Vomiting and diarrhea
Acute vomiting can typically be prevented with pre-treatment. Delayed vomiting is more common than acute in veterinary oncology patients. It is most common 2 to 5 days post-chemotherapy and seen with doxorubicin and the vinca alkaloids. Prevention is the goal, using both injectable anti-emetics at the time of treatment, and often oral medication in the following days.
Work-up may include CBC, chemistry panel, UA, +/- fecal floatations, and cultures. If abdominal pain is present, consider AXR or AUS to rule out foreign body, obstruction, and intussusception. For patients with GI neoplasia, it can be challenging to differentiate chemotherapy side effects from disease, and a good history can be key. It is helpful to determine when the GI side effects occurred in relation to chemotherapy treatment. For example, if the a cat with GI lymphoma had vomiting 12 days after chemotherapy, the cancer not the chemo is the likely cause.
Recommended outpatient treatment includes NPO, food and water trial, bland diet, anti-emetics, antibiotics with severe diarrhea, and a probiotic. It is important to discontinue oral chemotherapy or delay chemotherapy treatment, and recommend prophylactic therapy with the next chemotherapy.
For inpatients, Dr. Ettinger will add injectable antiemetics, IV fluid therapy, and IV antibiotics. At this point, she strongly encourages owners not to euthanize, saying that 1 to 2 days of good supportive care can result in a significant improvement.
Don’t monitor the bump or lump
Visual monitoring of skin and subcutaneous masses is not enough. Dr. Ettinger stressed that cancer is a cellular diagnosis, and therefore it is always recommended to evaluate masses that are growing, changing in appearance, or irritating to the patient.
“See Something Do Something. Why Wait? Aspirate. Dr. Sue Cancer Vet®” (SSDS) provides guidelines for evaluating superficial masses in dogs and cats. These guidelines will increase client awareness and will promote early cancer detection, diagnosis, and early surgical intervention.
See Something: When a skin mass is the size of a pea (1 cm) and has been present for at least 1 month,
Do Something: Aspirate or biopsy, and treat appropriately!
Obtaining a definitive diagnosis with cytology or biopsy early and before excision will lead to improved patient outcomes for superficial masses. When smaller, superficial tumours are detected early, surgery is likely curative – this is especially true for benign lesions and tumours that are only locally invasive with a low probability of metastasis. If tumours are removed with complete surgical margins, the prognosis is often good with no additional treatments needed.
- Pet owners need to be aware of the “pea” size requirement to have masses evaluated
- Veterinarians must measure and document the size of the mass in order to compare growth
- If > 1 cm (or size of large pea) and present for a month, the mass should be aspirated or biopsied
- Knowing the tumour type prior to the FIRST surgery will increase success of a curative-intent surgery
See Something Do Something, Copyright 2012 Dr. Sue Ettinger, All Rights Reserved. CVT
