Cancer Cachexia As a Manifestation of Malignancy*

SEPTEMBER 2006  VOL 8.8

Peer Reviewed

Editorial Mission Cancer Cachexia as a To provide busy practitioners with * concise, peer-reviewed recommendations Manifestation of Malignancy on current treatment standards drawn from published veterinary medical literature. Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine and Oncology) Director, Angel Care Cancer Center California Veterinary Specialists Carlsbad, California This publication acknowledges that President, Special Care Foundation for Companion Animals standards may vary according to individual San Marcos, California experience and practices or regional differences. The publisher is not responsible Antony S. Moore, BVSc, MVSc, DACVIM (Oncology) Co-Director, Veterinary Oncology Consultants Ltd for author errors. Wauchope, New South Wales, Australia Reviewed 2015 for significant advances Adjunct Professor, Faculty of Veterinary Science in medicine since the date of original University of Sydney publication. No revisions have been Consulting Oncologist, Animal Referral Hospital made to the original text. Sydney, Australia

ancer cachexia is a syndrome that affects many cancer patients. If not treated, it results in involuntary weight loss even when caloric intake is adequate. As with all Editor-in-Chief Cother paraneoplastic syndromes, this condition is a remote effect of cancer. Cancer Douglass K. Macintire, DVM, MS, cachexia has been shown to result in dramatic alterations in carbohydrate, lipid, and DACVIM, DACVECC protein metabolism before clinical evidence of cachexia is detectable. This syndrome is encountered by every practitioner who treats dogs with cancer but is often suspected Editorial Review Board only in patients with unexpected weight loss. Mark Bohling, DVM Dogs with cancer do not commonly have weight loss, although many have dramatic University of Tennessee alterations in metabolism regardless of the type, size, or stage of the cancer. These effects impair quality of life, response to therapy, and overall survival. The actual cause Harry W. Boothe, DVM, DACVS of cancer cachexia is the subject of a great deal of research. Auburn University Derek Burney, DVM, PhD, DACVIM MECHANISM Houston, TX The mechanisms of cancer cachexia are complex and include: Joan R. Coates, DVM, MS, DACVIM ••Starvation and malnutrition. University of Missouri Impaired oral intake. •• Curtis Dewey, DVM, DACVIM, DACVS Stomatitis, taste aversions, zinc deficiency. •• Plainview, NY ••Dehydration. ••Nausea. Nishi Dhupa, DVM, DACVECC ••Constipation. Cornell University ••Bowel obstruction. D. Michael Tillson, DVM, MS, DACVS ••Pain. Auburn University ••Impaired gastrointestinal absorption. ••Maldigestion. ••Exocrine pancreatic insufficiency.

*Adapted from Ogilvie GK, Moore AS: Managing the Canine Cancer Patient: A Practical Guide to Compassionate Care. Yardley, PA, Veterinary Learning Systems, 2006, pp 320–322. SEPTEMBER 2006  VOL 8.8

Dogs with untreated lymphoma have significantly higher free fatty acid, total triglyceride, and very-low-density lipoprotein and triglyceride serum concentrations compared with untreated control dogs. High-density lipoprotein cholesterol levels in dogs with lymphoma are significantly lower than those in control dogs. After doxorubicin treatment, dogs with lymphoma develop significantly elevated total cholesterol levels, as is noted in humans with cancer. Indirect calorimetry has been used in clinical cancer patients to quantify nutritional and water requirements. It demonstrates that energy expenditure and caloric needs in dogs with lymphoma and other malignancies are equal to or lower than those in normal dogs. Furthermore, it demonstrates that major or minor surgery fails to significantly increase the energy FIGURE 1. A Great Dane with osteosarcoma and dramatic weight expenditure of normal or cancer-bearing dogs. This is opposite loss despite adequate nutritional intake, the hallmark for the very of the common belief that animals and humans with cancer late stages of cancer cachexia. The metabolic alterations associated have elevated energy metabolism. with this condition occur even before clinical signs are noted and The above-mentioned alterations in carbohydrate, protein, continue after the animal is rendered free of the malignancy. Most and lipid metabolism are important to practitioners because dogs with the metabolic alterations associated with cancer cachexia they affect a diverse population of dogs with a wide variety of do not exhibit weight loss. cancers. Therapies to improve these changes must begin early and continue even after surgery or other treatment eliminates ••Diarrhea. the malignancy. ••Development of ascites, pleural effusion. ••Infections. DIAGNOSTIC CRITERIA ••Heart, lung, kidney failure. ••Prolonged deconditioning. Clinical Presentation ••Growth hormone deficiency. Dogs with cancer cachexia show few clinical signs of the paraneoplastic syndrome in the early stages. As the syndrome In addition to these items, profound alterations in carbohydrate progresses, weight loss is noted despite a good appetite (Figure 1). metabolism are seen in dogs and humans with cancer cachexia. Later, weight loss, anorexia, lethargy, and depression predominate. In dogs, elevated serum insulin and lactate concentrations Anorexia, fatigue, chronic nausea or vomiting, decreased associated with lymphoma and other malignancies rise higher activity level, and weight loss are a few of the obvious clinical still, compared with those in control dogs, in response to signs and clinical parameters associated with this condition. glucose-tolerance tests. Increased lactate and insulin levels in dogs with cancer do not normalize even when complete Diagnosis remission is obtained after doxorubicin chemotherapy or The changes in metabolism noted above can be documented surgery. Dogs with lymphoma have even higher lactate and early in the course of malignant disease. Dogs in the early insulin levels on reevaluation after relapse and show signs of phase of cancer cachexia may only show exercise intolerance, cachexia. Additional studies suggest that dogs with lymphoma lethargy, and anorexia. Later in the course of the disease, there may have a postreceptor defect, indicating that dietary therapy is overt wasting and loss of body condition despite adequate may be effective in combating the problem. Hyperlactatemia nutritional intake. Hypoalbuminemia is a notable finding in becomes more pronounced on administration of lactate- the later stages of the disease. The later stages are followed by containing parenteral fluids (e.g., lactated Ringer’s solution) death owing to failure of one or more organ systems. in dogs with lymphoma compared with control dogs. Dogs and humans with cancer show alterations in protein TREATMENT RECOMMENDATIONS and lipid metabolism that remain after chemotherapy or surgery achieves remission. Specifically, dogs with lymphoma ••The patient should consume an adequate quantity of highly have significant reductions in threonine, glutamine, glycine, bioavailable nutrients presented in a palatable form. valine, cystine, and arginine. In contrast, their isoleucine and ••A diet composed of modest amounts of complex carbohydrates, phenylalanine levels are significantly increased. Dogs and minimal quantities of rapidly absorbed simple carbohydrates, humans with cancer often have increased protein catabolism. relatively modest amounts of high-quality bioavailable Tumors produce proteolysis-inducing factor. proteins, and a modest amount of fats of the omega-3 (n-3)

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series may be ideal for supporting cancer patients without considering nasogastric, gastrostomy, or jejunostomy tube enhancing tumor growth. feeding. — Supplementing the diet with oils containing omega-3 or ••When enteral feeding is not feasible, parenteral feeding using with purified omega-3 fatty acids has been shown to slow minimal simple carbohydrates should be used. the growth of various types of cancers in animals. ••When possible, lactate- and glucose-containing fluids should — The efficacy of chemotherapeutic drugs, such as doxorubicin, be avoided because they may produce lactate and stimulate epirubicin, irinotecan, 5-fluorouracil, and tamoxifen, and release of insulin. An exception is in cases of septic shock or of radiation therapy has been improved when the diet during an insulin overdose, when glucose-containing fluids included omega-3 fatty acids. may be required specifically to treat hypoglycemia. — Omega-3 fatty acids induce beneficial effects in cancer ••Adequate calories should be provided; however, it may not be patients, such as modulation of eicosanoid production necessary to provide more nutrients than needed by disease- and inflammation, angiogenesis, proliferation, and free dogs. The following formula is a general approximation susceptibility for apoptosis. of the amount of metabolizable food to feed (kcal/day): 2(30 — Omega-3 fatty acids have been used to suppress cancer- × body weight [kg]) + 70. A more accurate formula is associated cachexia and to improve the quality of life. 70(body weight in kg0.75). ••Dogs should be fed enterally when possible. If appropriate, ••Frequent, small, energy-dense meals should be provided. methods such as warming the food, increasing palatability, ••Metoclopramide should be given when possible to reduce and using pharmacologic agents (e.g., megestrol acetate, nausea. Ondansetron may also be of value. benzodiazepine derivatives, cyproheptadine) to enhance ••The dog should be exercised regularly to maintain lean body appetite and stimulate oral feeding should be used before mass and to keep the attitude positive.

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