Tumoranorexie - Tumorkachexie bei ­gastrointestinalen Tumoren: Standards und Visionen

Zusammenfassung

Patienten mit Tumoren des Gastrointestinaltrakts - insbesondere mit einem Pankreaskarzinom - entwickeln regelhaft eine Fehl­ernährung, die wesentlich zur Morbidität und Mortalität beiträgt. Die gegenwärtigen Therapiemöglichkeiten geben dem behandelnden Arzt nur begrenzt die Möglichkeit zu einer erfolgreichen Behandlung und münden oftmals in einem therapeutischen Nihilismus. Prinzipiell ist zwischen einer Tumoranorexie und einer Tumorkachexie zu unterscheiden, oftmals liegt jedoch eine Kombination beider vor. In den letzten Jahren gelang es, die Pathophysiologie dieser Veränderungen weiter aufzuklären. Die vorliegende Übersicht möchte zum einen die momentanen Behandlungsmöglichkeiten aufzeigen, aber auch den aktuellen Kenntnisstand und mögliche neue Ansätze reflektieren.

Abstract

The development of progressive malnutrition or cachexia is frequent in patients with gastrointestinal cancer - especially in patients with a carcinoma of the pancreas. The cachexia syndrome which is characterised by loss of body weight, negative nitrogen balance and fatigue significantly affects patients’ quality of life, morbidity and survival. Because the currently established therapeutical strategies are often disappointing many physicians tended to develop a therapeutical nihilism. Cancer anorexia and cachexia are two distinct syndromes which may have synergistic effects in a patient. This review highlights the growing understanding of the multidimensional pathophysiological background. An algorithm of the current treatment strategies is given. In addition, we discuss new anabolic and anticatabolic agents (e. g. eicosapentanoic acid) and the results from first clinical trials.

Schlüsselwörter

Kachezeie - Karzinom - Pankreas - Ernährung - Ubiquitin - Fehl­ernährung

Key words

Cachexia - anorexia - cancer - pancreatic neoplasms - nutrition - nutrition disorders - gastrointestinal disease - ubiquitin

Literatur

• 1 Chamberlain R S, Fong Y. Nutritional and metabolic aspects of gastrointestinal cancer.  Curr Opin Clin Nutr Metab Care. 1999;  2 381-385
• 2 Cooperman A M, Chivati J, Chamberlain R S. Nutritional and metabolic aspects of pancreatic cancer.  Curr Opin Clin Nutr Metab Care. 2000;  3 17-21
• 3 Cooperman A M. Pancreatic cancer: the bigger picture.  Surg Clin North Am. 2001;  81 557-574
• 4 Grosvenor M, Bulcavage L, Chlebowski R T. Symptoms potentially influencing weight loss in a cancer population. Correlations with primary site, nutritional status, and chemotherapy administration.  Cancer. 1989;  63 330-334
• 5 Kotler D P. Cachexia.  Ann Intern Med. 2000;  133 622-634
• 6 Bischoff S C, Ockenga J, Manns M P. Artificial nutrition in intensive internal medicine. Chances and problems.  Internist (Berl). 2000;  41 1041-1061
• 7 Bozzetti F. Nutrition and gastrointestinal cancer.  Curr Opin Clin Nutr Metab Care. 2001;  4 541-546
• 8 Suttmann U, Ockenga J, Selberg O. et al . Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients.  J Acquir Immune Defic Syndr Hum Retrovirol. 1995;  8 239-246
• 9 Tisdale M J. Wasting in cancer.  J Nutr. 1999;  129 243-246
• 10 Nixon D W, Lawson D H, Kutner M. et al . Hyperalimentation of the cancer patient with protein-calorie undernutrition.  Cancer Res. 1981;  41 2038-2045
• 11 Evans W K, Nixon D W, Daly J M. et al . A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.  J Clin Oncol. 1987;  5 113-124
• 12 Potter J M, Roberts M A, McColl J H. et al . Protein energy supplements in unwell elderly patients - a randomized controlled trial.  JPEN J Parenter Enteral Nutr. 2001;  25 323-239
• 13 Boieng H. Kalzium und Antioxidantien als Supplemente in der Krebsprophylaxe - Statusbericht zu den Interventionsstudien.  Aktuelle Ernährungs Medizin. 2002;  26 130-136
• 14 Inui A. Cancer anorexia-cachexia syndrome: are neuropeptides the key?.  Cancer Res. 1999;  59 4493-4501
• 15 Plata-Salaman C R, Oomura Y, Kai Y. Tumor necrosis factor and interleukin-1 beta: suppression of food intake by direct action in the central nervous system.  Brain Res. 1988;  448 106-114
• 16 Yang Z J, Blaha V, Meguid M M. et al . Interleukin-1alpha injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and increases release of dopamine and serotonin.  Pharmacol Biochem Behav. 1999;  62 61-65
• 17 Mantovani G, Maccio A, Mura L. et al . Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites.  J Mol Med. 2000;  78 554-561
• 18 Ockenga J, Bischoff S C, Tillmann H L. et al . Elevated bound leptin correlates with energy expenditure in cirrhotics.  Gastroenterology. 2000;  119 1656-1662
• 19 Mantovani G, Maccio A, Massa E, Madeddu C. Managing cancer-related anorexia/cachexia.  Drugs. 2001;  61 499-514
• 20 Loprinzi C L, Schaid D J, Dose A M. et al . Body-composition changes in patients who gain weight while receiving megestrol acetate.  J Clin Oncol. 1993;  11 152-154
• 21 Bruera E, Neumann C M, Pituskin E. et al . Thalidomide in patients with cachexia due to terminal cancer: preliminary report.  Ann Oncol. 1999;  10 857-859
• 22 Goldberg R M, Loprinzi C L, Mailliard J A. et al . Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial.  J Clin Oncol. 1995;  13 2856-2859
• 23 Wigmore S J, Plester C E, Ross J A, Fearon K C. Contribution of anorexia and hypermetabolism to weight loss in anicteric patients with pancreatic cancer.  Br J Surg. 1997;  84 196-197
• 24 Mulligan H D, Beck S A, Tisdale M J. Lipid metabolism in cancer cachexia.  Br J Cancer. 1992;  66 57-61
• 25 Drott C, Persson H, Lundholm K. Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer.  Clin Physiol. 1989;  9 427-439
• 26 McDevitt T M, Todorov P T, Beck S A. et al . Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans.  Cancer Res. 1995;  55 1458-1463
• 27 Groundwater P, Beck S A, Barton C. et al . Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients.  Br J Cancer. 1990;  62 816-821
• 28 Hirai K, Hussey H J, Barber M D. et al . Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients.  Cancer Res. 1998;  58 2359-2365
• 29 Tisdale M J. Biomedicine. Protein loss in cancer cachexia.  Science. 2000;  289 2293-2294
• 30 Tisdale M J. Cancer anorexia and cachexia.  Nutrition. 2001;  17 438-442
• 31 Mitch W E, Goldberg A L. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway.  N Engl J Med. 1996;  335 1897-1905
• 32 Guttridge D C, Mayo M W, Madrid L V. et al . NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.  Science. 2000;  289 2363-2366
• 33 Todorov P, Cariuk P, McDevitt T. et al . Characterization of a cancer cachectic factor.  Nature. 1996;  379 739-742
• 34 Smith H J, Lorite M J, Tisdale M J. Effect of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts: modula­tion by eicosapentaenoic acid.  Cancer Res. 1999;  59 5507-5513
• 35 Kawamura I, Morishita R, Tomita N. et al . Intratumoral injection of oligonucleotides to the NF kappa B binding site inhibits cachexia in a mouse tumor model.  Gene Ther. 1999;  6 91-97
• 36 Mitch W E, Price S R. Transcription factors and muscle cachexia: is ­there a therapeutic target?.  Lancet. 2001;  357 734-735
• 37 Combaret L, Ralliere C, Taillandier D. et al . Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats.  Mol Biol Rep. 1999;  26 95-101
• 38 Keifer J A, Guttridge D C, Ashburner B P. et al . Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity.  J Biol Chem. 2001;  276 22382-22387
• 39 Ockenga J, Rohde F, Suttmann U. et al . Ketotifen in HIV-infected pa­tients: effects on body weight and release of TNF-alpha.  Eur J Clin Pharmacol. 1996;  50 167-170
• 40 Hussey H J, Tisdale M J. Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentaenoic acid.  Br J Cancer. 1999;  80 1231-1235
• 41 Sauer L A, Dauchy R T, Blask D E. Mechanism for the antitumor and anticachectic effects of n-3 fatty acids.  Cancer Res. 2000;  60 5289-5295
• 42 Pirlich M, Muller C, Sandig G. et al . Increased proteolysis after single-dose exposure with hepatotoxins in HepG2 cells.  Free Radic Biol Med. 2002;  15 283-291 (33)
• 43 Pirlich M, Kiok K, Sandig G. et al . Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells.  Neurosci Lett. 2002 Aug 9;  328 (2) 93-96
• 44 Price S A, Tisdale M J. Mechanism of inhibition of a tumor lipid-mobi­lizing factor by eicosapentaenoic acid.  Cancer Res. 1998;  58 4827-4831
• 45 James M J, Gibson R A, Cleland L G. Dietary polyunsaturated fatty acids and inflammatory mediator production.  Am J Clin Nutr. 2000;  71 343S-348S
• 46 Hussey H J, Tisdale M J. Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model.  Int J Cancer. 2000;  87 95-100
• 47 Barber M D, Ross J A, Voss A C. et al . The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer.  Br J Cancer. 1999;  81 80-86
• 48 Barber M D, McMillan D C, Preston T. et al . Metabolic response to feed­ing in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement.  Clin Sci (Colch). 2000;  98 389-399
• 49 Gogos C A, Ginopoulos P, Salsa B. et al . Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial.  Cancer. 1998;  82 395-402
• 50 McMillan D C, Wigmore S J, Fearon K C. et al . A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.  Br J Cancer. 1999;  79 495-500