Palliative Care for Cancer Patients
ACVIM 2008
Dennis Bailey, DVM, DACVIM (Oncology)
Ithaca, NY, USA

Introduction

Veterinary oncology is a rapidly evolving field, and advances continually are being made to improve our ability to diagnose and treat cancer. Having said that, neoplasia still remains one of the most common causes of death and euthanasia in companion animals.1 For several common forms of cancer such as lymphoma and osteosarcoma, aggressive treatment consistently provides extended periods of excellent quality of life but only rarely provides a cure. Additionally, many pets diagnosed with cancer never undergo definitive cancer therapy either because they are not good candidates or because of owner choice. For those patients not undergoing definitive therapy, it is important to provide palliative care to provide and sustain excellent quality of life for as long as possible.

Palliative care refers to supportive care provided with the intent of improving or maintaining quality of life, without necessarily slowing the progression of the cancer or prolonging life. In contrast, definitive therapy refers to aggressive treatment that is administered with the goal of trying to slow cancer progression and prolong life. (It is important to recognize a treatment is defined as palliative or definitive based on the intended outcome, not the actual outcome.) Palliative care should not be regarded as "giving up." Some patients with advanced-stage do not benefit from more aggressive definitive-intent therapy. For example, when dogs with metastatic osteosarcoma are treated with definitive-intent therapy, survival times are comparable to those achieved with palliative care alone.2 Conversely, palliative care also should not be regarded as "enabling the owner to prolong the inevitable." If a pet's quality of life is sub-optimal and cannot be restored with palliative care, then humane euthanasia should be recommended. However, palliative care often is very effective at restoring quality of life or prolonging excellent quality of life. Additionally, whenever palliative care is being provided, close client communication is essential to ensure that quality of life is being maintained.

Nutritional Support

Malnutrition is a common complication of cancer. A recent veterinary study indicated that while only 4% of dogs with cancer were emaciated (defined as body conditioning score < 3 out of 9) at the time of initial diagnosis, 68% had documented evidence of weight loss and 15% had moderate to severe muscle wasting.3 Cancer cachexia is a complex metabolic syndrome characterized by weight loss, anorexia, and wasting of lean body mass secondary to the growing malignancy. The factors contributing to cancer cachexia can be divided into two broad categories. The first category includes mechanical and functional abnormalities that lead to decreased nutrient intake. Oral tumors can cause dysphagia and considerable pain. Gastrointestinal tumors can cause pain, early satiety, mechanical obstruction, nausea, vomiting, diarrhea, and malabsorption of nutrients. Advanced-stage neoplasia, regardless of its anatomic location, often is associated with partial or complete anorexia. The second group of factors contributing to cancer cachexia includes numerous metabolic derangements that prevent the body from efficiently using the nutrients that it has. Abnormalities in the way the body uses carbohydrates, proteins, and lipids have all been identified. The result is that a cancer patient can lose weight and lean muscle mass even in the face of adequate food intake. The underlying mechanisms for these metabolic derangements are not completely understood, but substances released by the tumor itself and by the patient's body in response to the tumor are both thought to play important roles.4

A patient's nutritional assessment is based on both a thorough history and physical examination. It is important to ask an owner about his or her pet's usual dietary habits, including the type of food fed, the amount fed at each meal, the number of meals per day, the types and amounts of treats given, and the voraciousness of the pet's appetite. The owner should then be asked about any recent changes in dietary habits as well as any changes in body weight or body conditioning. Physical examination should then be used to objectively assess weight, body condition, and muscle mass. If available in the medical record, previous assessments should be used as a baseline for comparison. Early changes associated with cancer cachexia may be as subtle as the pet not finishing its food as quickly as usual or requiring some coaxing. As cancer cachexia progresses, the pet's nutritional intake will become inadequate despite coaxing and offering more palatable foods, and eventually weight loss and muscle wasting will become evident.

How aggressively to provide nutritional support depends on the severity of the patient's nutritional deficiencies. Minimal deficiencies can be overcome by offering palatable foods such as Hills a/d® or boiled chicken and rice. (The latter is not nutritionally balanced, and additional supplements are needed if this diet is going to be used long-term.) For moderate anorexia, appetite stimulants such as prednisone, cyproheptadine, and mirtazapine can be used. If food intake is thought to be reduced because of nausea, gastroprotectants such as famotidine and sucralfate should be considered. Anti-emetics such as metoclopramide, dolasetron, ondansetron, and maropitant are indicated to help control nausea and vomiting.

If voluntary food intake cannot be restored or maintained at adequate levels, then supplemental feeding is needed. Whenever possible, it is preferable to use the GI tract. This way, the nutrients provided are digested and metabolized through their normal pathways. In addition, food within the intestine plays a critical role in maintaining gut health and function. The most commonly used feeding tubes are esophagostomy tubes and gastrostomy tubes. Both tubes can be left in place indefinitely. The main advantage of an esophagostomy tube is the ease of placement--they can be placed quickly and easily under light general anesthesia without any specialized equipment. In contrast, gastrostomy tube placement usually is done surgically or with endoscopic guidance. The main advantage of a gastrostomy tube is that it is wider in diameter and can accommodate a wider variety of foods. Additionally, low-profile gastrostomy tubes can be used to eliminate the need for cumbersome and potentially uncomfortable bandages.

There is a lot of discussion about so-called "cancer diets." The general features of these diets include low quantities of simple carbohydrates, moderate quantities of highly digestible proteins rich in arginine and glutamine, and relatively high quantities of lipids and omega-3-fatty acids.5 However, the use of such diets has been evaluated only in dogs with lymphoma, and the clinical benefit was questionable.6 The author believes it is more important for a patient's diet to be palatable and nutritionally balanced. Changing a pet's diet to a cancer diet should be considered only if caloric and general nutritional requirements are being maintained without any difficulty. Remember, get the patient to eat first; worry about what it is eating second.

Pain Management

Cancer pain is one of the most important factors affecting overall quality of life. In human oncology, it is estimated that cancer pain is experienced by 30-50% of people undergoing active cancer treatment and 70-90% of people with advanced disease.7 It is difficult to accurately assess the prevalence of pain in veterinary cancer patients, but it is reasonable to assume that it is comparable to that reported in people. Cancer pain likely is underappreciated in veterinary cancer patients because it is relatively difficult to assess objectively. Physiologic variables such as heart rate, respiratory rate, and pupil size are not reliable indicators of pain. Instead, pain assessment is based primarily on behavior. Subtle changes in activity level, attitude, appetite, or grooming can be early signs of pain. As pain becomes more severe, aversion to petting/palpation may be noticed. Vocalization usually is seen only when pain is severe. Because the owner sees the pet every day in its own environment, he or she is best able to assess behavior changes. Therefore, it is crucial to educate the owner about what signs to look for, to ask the owner for feedback on a regular basis, and to trust the information provided by the owner.

It is very important to always be aware of the potential for cancer pain and to take a proactive approach with respect to its diagnosis and treatment. Pain can be prevented far more easily than it can be reversed. Chronic pain induces physical changes in the spinal cord that alter the way pain signals are processed, resulting in hyperalgesia and allodynia. These changes also decrease the efficacy of analgesic medications, making it much more difficult to alleviate a patient's pain. Additionally, even if the pain eventually is controlled, the physical changes in the spinal cord are not necessarily fully reversible.

Pain management typically is most effective when multiple treatment modalities are used in combination. The World Health Organization has outlined a three-step hierarchy for the management of cancer pain. Adapting this scheme to veterinary patients, when pets present with mild pain non-opioid analgesics such as nonsteroidal anti-inflammatory drugs (carprofen, deracoxib, meloxicam) should be attempted first. For moderate pain, a weak opioid such as codeine, buprenorphine, or tramadol can be added on. For severe pain, strong opioids such as morphine or fentanyl are indicated. While veterinary analgesia centers around the use of nonsteroidal anti-inflammatory drugs and opioids, the adjunct use of additional drugs such as gabapentin and amantadine is gaining popularity.

In addition to using analgesics, several other treatment modalities should be considered and used whenever appropriate. Local anesthetic nerve blocks are very useful for orofacial tumors and for phantom pain associated with amputation. Using a mixture of bupivacaine, lidocaine, methylprednisolone, and serapin, we have seen good locoregional pain control enduring for up to 1 month per injection.

Bisphosphonates are drugs that prevent bone resorption by inhibiting the formation of new osteoclasts, inhibiting the ability of mature osteoclasts to resorb bone, and inducing osteoclast apoptosis.8,9 By inhibiting tumor-associated osteolysis, bisphosphonates can help reduce the pain associated with both primary and metastatic bone tumors. Pamidronate currently is the bisphosphonate used most commonly in veterinary medicine. A dosage of 1.0-2.0 mg/kg every 4 weeks has been reported.10,11 To minimize the risk of renal toxicity, the pamidronate dose should be diluted in 250 mL 0.9% NaCl and then administered intravenously over 2 hours. In one study, 12 out of 43 dogs (28%) with appendicular osteosarcoma experienced clinically significant pain relief that persisted for > 4 months.10 There also is anecdotal evidence that the oral bisphosphonate alendronate may be beneficial for dogs with osteosarcoma, but its routine use is not recommended because of poor absorption from the gastrointestinal tract.9

Palliative Radiation Therapy

Palliative radiation therapy protocols are delivered with the intent of alleviating pain or another side effect associated with an incurable tumor. Palliative radiation therapy typically is reserved for pets that have a decreased quality of life from the presence of a tumor but would not be expected to benefit from a more aggressive definitive course of radiation treatment.

Radiation therapy protocols are defined as definitive or palliative based on the total radiation dose and fractionation scheme.12 Definitive protocols typically involve the delivery of 2.25 to 3.20 Gy/fraction on a Monday through Friday basis for a total of 16 to 25 treatments and a total dose of 48 to 63Gy. Palliative radiation protocols typically involve the administration of a larger dose per fraction, but a fewer total number of fractions and lower total radiation dose. A variety of palliative protocols exist. One of the most commonly used protocols is 8 Gy/fraction, given once weekly for 4 consecutive weeks for a total dose of 32 Gy. Another involves 5 Gy/fraction once daily for 5 consecutive days for a total dose of 20 Gy. Palliative protocols typically are associated with minimal to no acute adverse effects such as moist desquamation of the skin or oral mucositis. The larger dose per fraction does increase the risk for late adverse effects, but most animals receiving palliative radiation therapy typically do not live long enough to develop late effects.

Palliative radiation therapy has been studied most thoroughly for the treatment of canine osteosarcoma.13-15 Approximately 75-90% of dogs experience pain relief based on an improvement in lameness. The median time from when radiation therapy is initiated to when lameness improves is around 14 days (range, 1 to 60 days). Median duration of analgesia is around 2-4 months, but individuals have enjoyed considerably longer periods of pain relief. Palliative radiation therapy also has been effectively used to treat oral tumors,16 nasal tumors,17 thyroid carcinomas,18 and soft tissue sarcomas.19

Prednisone

It is often joked that no patient should die without the benefit of steroids, but for many cancer patients this is true. Prednisone can be used as a chemotherapy drug for some forms of cancer. When dogs with lymphoma are treated with single-agent prednisone, approximately half will attain either a partial or complete remission. Remissions usually are transient, though, and survival times typically are around 1-2 months.20 Prednisone can be used for cats with lymphoma, although in the author's experience response rates are even lower, and survival times are usually <1 month. Canine mast cell tumors also can be treated palliatively with single-agent prednisone. Approximately 20% of dogs will enjoy a partial or complete remission.21 Response durations are variable, but usually persist for a few weeks to a few months. It is critical to always reach a definitive diagnosis of cancer before placing a patient on a palliative course of steroids. While response rates to prednisone are low, the responses that do occur can be quite dramatic, particularly for dogs with lymphoma. It is not uncommon for an owner to change his or her mind and request that more aggressive therapy be initiated after seeing a marked response to prednisone. However, reaching a definitive diagnosis once the patient is in a partial or complete remission can be difficult or impossible, and it is malpractice to initiate aggressive cytotoxic chemotherapy without a definitive diagnosis of cancer. Additionally, before starting a course of palliative steroids, owners always should be counseled that if they decide to pursue more aggressive chemotherapy at a future time, pretreatment with steroids can induce multidrug resistance mechanisms that diminish the efficacy of chemotherapy.22

The anti-inflammatory effects of prednisone can be very beneficial as well. Tumors often can induce an inflammatory response, and this secondary peritumoral inflammation and edema can have a significant clinical impact. For example, in dogs and cats with brain tumors, an anti-inflammatory course of prednisone can dramatically improve clinical signs for up to a few months.23 In the author's experience, prednisone also can reduce the congestion and stertorous breathing often seen in animals with nasal tumors, as well as the coughing associated with pulmonary metastasis. Prednisone also can help maintain quality of life by improving appetite and energy level.

Final Thoughts

Palliative care is about quality of life. Alleviate anything that is hindering quality of life, and try to prevent future hindrances from arising. There is no single best palliative treatment plan. The plan chosen will depend on the tumor type, the tumor location, the patient's clinical signs, and the owner's goals. Because there are so many variables involved, close communication between the veterinary staff and the owner is vital. The owner sees his or her pet in its own environment every day and therefore will recognize subtle changes more quickly. This feedback can then be used by the veterinary staff to modify the palliative treatment plan as needed to ensure optimal patient care. At the same time, this feedback will help strengthen the bond between the client and veterinarian. This bond becomes even more important when quality of life can no longer be maintained, and the conversation turns to euthanasia. The strong trust that has been fostered will allow the owner to realize that you have his or her pet's best interest at heart and take comfort in the knowledge that everything was done to provide his or her family member with the best possible quality of life for as long as possible.

References

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Speaker Information
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Dennis Bailey, Jr., DVM, DACVIM (Oncology)
Ithaca, NY


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