Page 322 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

300 PART III Therapeutic Modalities for the Cancer Patient

anti-NGF monoclonal antibody therapy has been tested in clini- survival times (STs), or tumor burden, suggesting that lymphoma was
cal pilot studies in both dogs and cats with OA; analgesic relief not sensitive to this basic dietary alteration. 252 During this study the
70
REE and RQ assessed during treatment did not change significantly
without associated side effects was achieved. Nevertheless, more
VetBooks.ir preclinical and clinical evaluations need to be performed to pro- when the tumor burden was eliminated through chemotherapy, sug-
gesting that no significant changes occurred in energy expenditure
vide a better understanding of the potential role of such a targeted
agent in small animal clinical practice. or metabolism. These data collectively indicate that removal of the
tumor burden does not alter the resting energy requirement (RER)
and that no fundamental differences were observed between normal
SECTION B: NUTRITIONAL MANAGEMENT OF healthy dogs and dogs with lymphoma.
THE CANCER PATIENT Canine nonhematopoietic malignancies were also examined
in this context before and 4 to 6 weeks after excision of the pri-
mary tumors (including mammary carcinoma, OSA, high-grade
JOSEPH WAKSHLAG mast cell tumors [MCTs], and lung carcinoma). As in dogs with
lymphoma, the REE was no different from that of control dogs,
Over the past 80 years the examination of nutrients and their rela- and no difference in REE was seen before and after excision of
tionship to cancer and cancer prevention has led to a better under- the primary tumor, suggesting no futile cycling of energy in these
standing of how nutrition may play a role in the management of patients. 253 Interestingly, the RQ values were above 0.8 for all con-
the disease. The paucity of well-controlled studies in companion trol and tumor-bearing dogs, suggesting that the resting energy
animals and the extrapolation of data derived from humans stud- was not from lipolysis; this was contradictory to a follow-up study
ies in the investigation of uncommon tumor types in companion performed in dogs with OSA. In dogs with OSA, a difference was
animals (colon, prostate, pancreas) are frustrating and make general observed in the REE; affected dogs had a higher REE than control
recommendations for nutritional interventions challenging. How- dogs, and the RQ was closer to 0.7 in both affected and control
ever, owners often wish to alter their pets’ feeding regimen, regardless dogs. 254 This increased REE was still present after excision of the
of proven efficacy. That said, three areas of nutrition often are dis- primary lesion, suggesting that the modest increase in REE was
cussed with clients: modification of tumor metabolism; adjustment due to factors other than the primary neoplasia and could possibly
of nutritional risk factors that may affect outcomes; and nutritional be associated with micrometastasis, inflammation associated with
intervention during therapy. All of these are addressed in this section. neoplastic disease, or heightened pain response associated with the
primary tumor and surgical procedure. 254 These findings were sur-
Metabolism of Cancer prising in light of the previously mentioned studies but likely were
more valid considering that the REE calculations were based on
Substrate Utilization lean mass rather than total kilograms of body weight in the OSA
study. 254 In general, fat mass is considered to be metabolically
Numerous neoplastic cell lines have been propagated successfully inert; therefore an REE based on lean body mass is more appropri-
in cell culture, allowing examination of cellular behavior. One ate. The previous studies in nonhematopoietic malignancies and
fundamental finding from cell culture is that most neoplastic cells lymphoma did not adjust for body condition or lean body mass in
propagate better in a high-glucose media. This likely is due to tumor-bearing or normal populations, 252,253 and the inability to
limited fatty acid metabolism coupled with increases in metabolic document differences in REE noted in these two studies may have
pathways that utilize glucose; this traditionally has been termed been at least partly due to a lack of body condition assessment.
the “Warburg effect,” after Otto Warburg’s seminal work suggest- Metabolic changes were observed in dogs with OSA in addi-
ing that glycolysis is the primary pathway for energy production in tion to an increased REE. Alterations in glucose metabolism
neoplastic cells. 246,247 Studies in humans have shown that certain (potentially higher glucose turnover), increased protein turnover,
cancer patients liberate excessive lactate from solid tumors, 248,249 and urinary protein losses in affected dogs were also observed. 254
providing evidence that glycolysis and pyruvate production are Studies in dogs with lymphoma identified alterations in carbo-
critical to neoplastic cell metabolism. This has led to the Cori hydrate metabolism, such as increased serum lactate, and insulin
cycle hypothesis of neoplasia; that is, neoplastic tissue, much like concentrations during glucose tolerance testing suggesting insulin
skeletal muscle tissue, appears to undergo regeneration of glucose resistance. 251,255,256 This may be partially explained by aberrant
from lactate through hepatic resynthesis of glucose. 250 Unfortu- interleukin-6 (IL-6) cytokine influences on glucose metabolism
nately, this regeneration of glucose is an energy-costly cycle and is resulting in insulin resistance in dogs with lymphoma. 257 Insulin
thought to contribute to increases in resting energy requirements. insensitivity and serum lactate did not change once remission was
In veterinary medicine a significant body of work has examined achieved in one of the previously mentioned studies. 251 Addition-
metabolism and cancer, often through the application of indirect ally, mild alterations in lipid metabolism in dogs with lymphoma
calorimetry assessments to study whole body metabolism. Such stud- were seen as higher basal triglyceride and cholesterol concentra-
ies investigate oxygen consumption and carbon dioxide liberation; tions compared with control dogs, 258 and treatment with doxo-
the ratios of carbon dioxide production to oxygen consumption can rubicin lowered serum cholesterol, perhaps as a result of hepatic
provide estimates of energy consumption (resting energy expendi- effects of the chemotherapy 258 ; however, the dyslipidemia was
ture [REE]) and substrate utilization (respiratory quotient [RQ]). not ameliorated once the primary tumor burden was eliminated,
In one study healthy dogs displayed a higher REE than dogs with which is logical in light of the insulin resistance observed.
stage III or stage IV lymphoma. 251 RQ values between the groups
were no different, suggesting that the dogs were all burning similar Anorexia and Cachexia
substrate and that the dogs with lymphoma were not preferentially
burning more glucose than their control counterparts. 251 Dogs with Anorexia is common in cancer patients. In some patients this
lymphoma that were fed either a high-fat or a high-carbohydrate diet may be partially explained by adverse events associated with the
during doxorubicin chemotherapy did not differ in remission times, use of chemotherapy. Chemotherapeutics can cause a variety of