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Therapy Insight: cancer anorexia–cachexia syndrome—when all you can eat is yourself

Abstract

Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia–cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass—and to a lesser extent adipose tissue—occurring even before weight loss becomes apparent. Cancer anorexia–cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic–cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

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Figure 1: Diagram showing the modulation of food intake via the hypothalamus.
Figure 2: The balance between prophagic and anorexigenic signaling in the arcuate nucleus of the brain.
Figure 3: Anorexia improvements via oral supplements that compete with tryptophan to inhibit serotonergic signaling.

References

  1. Ayers M et al. (2004) Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 22: 2284–2293

    CAS  Article  Google Scholar 

  2. Tisdale MJ (2002) Cachexia in cancer patients. Nat Rev Cancer 2: 862–871

    CAS  Article  Google Scholar 

  3. Bossola M et al. (2001) Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am J Physiol Regul Integr Comp Physiol 280: R1518–R1523

    CAS  Article  Google Scholar 

  4. Bozzetti F et al. (1999) Artificial nutrition in cancer patients: which route, what composition? World J Surg 23: 577–583

    CAS  Article  Google Scholar 

  5. Norton JA et al. (1981) Whole body protein synthesis and turnover in normal man and malnourished patients with and without known cancer. Ann Surg 194: 123–128

    CAS  Article  Google Scholar 

  6. Lundholm K et al. (1982) Efflux of 3-methylhistidine from the leg in cancer patients who experience weight loss. Cancer Res 42: 4802–4811

    Google Scholar 

  7. Lundholm K et al. (1976) Skeletal muscle metabolism in patients with malignant tumour. Eur J Cancer 12: 465–473

    CAS  Article  Google Scholar 

  8. Warren RS et al. (1985) Protein synthesis in the tumor-influenced hepatocyte. Surgery 98: 275–282

    CAS  PubMed  Google Scholar 

  9. Lecker SH et al. (1999) Muscle protein breakdown and critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr 129 (Suppl 1S): 227S–237S

    CAS  Article  Google Scholar 

  10. Goll DE et al. (1992) Role of the calpain system in muscle growth. Biochimie 74: 225–237

    CAS  Article  Google Scholar 

  11. Drott C et al. (1989) Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer. Clin Physiol 9: 427–439

    CAS  Article  Google Scholar 

  12. Bing C et al. (2000) Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. Cancer Res 60: 2405–2410

    CAS  PubMed  Google Scholar 

  13. Todorov P et al. (1996) Characterization of a cancer cachectic factor. Nature 379: 739–742

    CAS  Article  Google Scholar 

  14. Russell ST et al. (2002) Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor. Br J Cancer 86: 424–428

    CAS  Article  Google Scholar 

  15. Ramos EJ et al. (2004) Cancer anorexia–cachexia syndrome: cytokines and neuropeptides. Curr Opin Clin Nutr Metab Care 7: 427–434

    CAS  Article  Google Scholar 

  16. Schwartz MW et al. (2000) Central nervous system control of food intake. Nature 404: 661–671

    CAS  Article  Google Scholar 

  17. Laviano A et al. (2003) Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol 4: 686–694

    CAS  Article  Google Scholar 

  18. Stubbs RJ et al. (2000) The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr 84: 405–415

    CAS  Article  Google Scholar 

  19. Rossi Fanelli F et al. (1986) Plasma tryptophan and anorexia in human cancer. Eur J Cancer Clin Oncol 22: 89–95

    CAS  Article  Google Scholar 

  20. Muscaritoli M et al. (2004) Therapy of muscle wasting: what is the future? Curr Opin Clin Nutr Metab Care 7: 459–466

    CAS  Article  Google Scholar 

  21. Bruera E et al. (2003) Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. J Clin Oncol 21: 129–134

    CAS  Article  Google Scholar 

  22. Laviano A and Meguid MM (1996) Nutritional issues in cancer management. Nutrition 12: 358–371

    CAS  Article  Google Scholar 

  23. Geels P et al. (2000) Palliative effect of chemotherapy: objective tumor response is associated with symptom improvement in patients with metastatic breast cancer. J Clin Oncol 18: 2395–2405

    CAS  Article  Google Scholar 

  24. Sutton LM et al. (2003) Management of terminal cancer in elderly patients. Lancet Oncol 4: 149–157

    Article  Google Scholar 

  25. Walsh D et al. (2000) The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Support Care Cancer 8: 175–179

    CAS  Article  Google Scholar 

  26. DeWys WD et al. (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 69: 491–497

    CAS  Article  Google Scholar 

  27. Palesty JA and Dudrick SJ (2003) What we have learned about cachexia in gastrointestinal cancer. Dig Dis 21: 198–213

    CAS  Article  Google Scholar 

  28. Ruiz-Arguelles GJ et al. (2004) Multiple myeloma in Mexico: a 20-year experience at a single institution. Arch Med Res 35: 163–167

    Article  Google Scholar 

  29. Thammakumpee K (2004) Clinical manifestation and survival of patients with non-small cell lung cancer. J Med Assoc Thai 87: 503–507

    PubMed  Google Scholar 

  30. Walsh D et al. (2002) Symptoms and prognosis in advanced cancer. Support Care Cancer 10: 385–388

    Article  Google Scholar 

  31. Ravasco P et al. (2004) Cancer: disease and nutrition are key determinants of patients' quality of life. Support Care Cancer 12: 246–252

    Article  Google Scholar 

  32. Cherny NI and Catane R (2003) Attitudes of medical oncologists toward palliative care for patients with advanced and incurable cancer: report on a survey by the European Society of Medical Oncology Taskforce on Palliative and Supportive Care. Cancer 98: 2502–2510

    Article  Google Scholar 

  33. Isenring EA et al. (2004) Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and neck area. Br J Cancer 91: 447–452

    CAS  Article  Google Scholar 

  34. Feinle C et al. (2003) Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans. Am J Physiol Gastrointest Liver Physiol 284: G798–G807

    CAS  Article  Google Scholar 

  35. Inui A (2002) Cancer anorexia–cachexia syndrome: current issues in research and management. CA Cancer J Clin 52: 72–91

    Article  Google Scholar 

  36. Pascual Lopez A et al. (2004) Systematic review of megestrol acetate in the treatment of anorexia–cachexia syndrome. J Pain Symptom Manage 27: 360–369

    Article  Google Scholar 

  37. Jho DH et al. (2004) Role of omega-3 fatty acid supplementation in inflammation and malignancy. Integr Cancer Ther 3: 98–111

    CAS  Article  Google Scholar 

  38. Fearon KC et al. (2003) Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 52: 1479–1486

    CAS  Article  Google Scholar 

  39. Moses AW et al. (2004) Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer 90: 996–1002

    CAS  Article  Google Scholar 

  40. Jatoi A et al. (2004) An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J Clin Oncol 22: 2469–2476

    CAS  Article  Google Scholar 

  41. Burns CP et al. (2004) Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia. Cancer 101: 370–378

    CAS  Article  Google Scholar 

  42. Torelli GF et al. (1999) Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats. Am J Physiol 277: R850–R855

    CAS  PubMed  Google Scholar 

  43. Trikha M et al. (2003) Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 9: 4653–4665

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Eleutherakis-Papaiakovou V et al. (2004) Thalidomide in cancer medicine. Ann Oncol 15: 1151–1160

    CAS  Article  Google Scholar 

  45. Eichhorst ST et al. (2004) Suramin inhibits death receptor-induced apoptosis in vitro and fulminant apoptotic liver damage in mice. Nat Med 10: 602–609

    CAS  Article  Google Scholar 

  46. Diksic M and Young SN (2001) Study of the brain serotonergic system with labelled α-methyl-L-tryptophan. J Neurochem 78: 1185–1200

    CAS  Article  Google Scholar 

  47. Cangiano C et al. (1996) Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. J Natl Cancer Inst 88: 550–552

    CAS  Article  Google Scholar 

  48. Hiroshige K et al. (2001) Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis. Nephrol Dial Transplant 16: 1856–1862

    CAS  Article  Google Scholar 

  49. Marchesini G et al. for the Italian BCAA Study Group. (2003) Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 124: 1792–1801

    CAS  Article  Google Scholar 

  50. Heisler LK et al. (2002) Activation of central melanocortin pathways by fenfluramine. Science 297: 609–611

    CAS  Article  Google Scholar 

  51. Marks DL et al. (2003) Differential role of melanocortin receptor subtypes in cachexia. Endocrinology 144: 1513–1523

    CAS  Article  Google Scholar 

  52. Smith HJ et al. (2004) Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice. Br J Cancer 91: 408–412

    CAS  Article  Google Scholar 

  53. Inui A et al. (2004) Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J 18: 439–456

    CAS  Article  Google Scholar 

  54. Shimizu Y et al. (2003) Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 9: 774–778

    CAS  PubMed  Google Scholar 

  55. Neary NM et al. (2004) Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89: 2832–2836

    CAS  Article  Google Scholar 

  56. Cahlin C et al. (2000) Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cachexia related to prostanoids. Cancer Res 60: 1742–1749

    CAS  PubMed  Google Scholar 

  57. Lundholm K et al. (2004) Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: effects on survival, metabolism, and function. Cancer 100: 1967–1977

    CAS  Article  Google Scholar 

  58. Inui A (1999) Cancer anorexia–cachexia syndrome: are neuropeptides the key? Cancer Res 59: 4493–4501

    CAS  PubMed  Google Scholar 

Download references

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Correspondence to Alessandro Laviano.

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F Rossi-Fanelli received a research grant from the Ross Products Division of Abbott Laboratories, Columbus, Ohio, USA. Abbott Laboratories produces a caloric supplement enriched with fish oil.

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Laviano, A., Meguid, M., Inui, A. et al. Therapy Insight: cancer anorexia–cachexia syndrome—when all you can eat is yourself. Nat Rev Clin Oncol 2, 158–165 (2005). https://doi.org/10.1038/ncponc0112

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