Skip to main content

Advertisement

SpringerLink
Log in

New drugs for the anorexia-cachexia syndrome

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Anorexia and cachexia accompany advancing cancer to a greater extent than any other symptom. Cachexia alone causes 22% of cancer deaths. The pathophysiology of cachexia is distinctly different from that of starvation. Resting energy expenditures are elevated, and abnormal intermediary metabolism, proteolysis, and lipolysis occur independently of caloric intake. A facilatative interaction between catecholamines, prostaglandins, and inflammatory cytokines is responsible for cachexia. Successful treatment requires reduction of energy expenditures, reversal of anorexia, and correction of abnormal intermediary metabolism, lipolysis, and proteolysis. Multiple appetite stimulants can be used in combination. Several new potentially useful biologic agents have been tested in animal tumor models. Several of the anticachectic agents have demonstrated in vivo or in vitro antitumor activity. The biologic and clinical activity of each drug is reviewed herein, and potentially useful combinations are listed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Argiles J, Meijsing S, Pallares-Trujillo J, et al.: Cancer cachexia: a therapeutic approach. Med Res Rev 2001, 21:83–101. The authors provide a concise review that covers major areas of treatment.

    Article  PubMed  CAS  Google Scholar 

  2. Warren S: The immediate cause of death in cancer. Am J Med Sci 1932, 184:610–613.

    Article  Google Scholar 

  3. Barton B: IL-6-like cytokines and cancer cachexia: consequences of chronic inflammation. Immunologic Res 2001, 23:41–58.

    Article  CAS  Google Scholar 

  4. Cravo M, Gloria L, Claro I: Metabolic responses to tumor disease and progression: tumor-host interaction. Clin Nutr 2000, 19:469–465. This article is a good overall review of the pathophysiology of cachexia. The figure within the text is an excellent visualization of the entire cachexic-anorexic process.

    Article  Google Scholar 

  5. Goldberg R, Loprinzi C: Cancer anorexia/cachexia. Cancer Treat Res 1999, 100:31–41.

    PubMed  CAS  Google Scholar 

  6. Harvie M, Campbell I: Energy balance, cancer and the sympathetic nervous system. Eur J Cancer 2000, 36:289–292. The authors provide a summary of energy expenditures and thermagenesis in advanced cancer patients which is necessary to understand the benefits of NSAIDs and beta blockers. The association of acutephase proteins with REEs was new to me.

    Article  PubMed  CAS  Google Scholar 

  7. Bosaeus I, Daneryd P, Svanberg E, et al.: Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients. Int J Cancer 2001, 93:380–383. The authors nicely demonstrate that one of the initial events in cachexia is not anorexia but the failure of the expected upregulation of dietary intake in response to elevated energy expenditures. There is a plethora of information in this article. I had too many notes over the pages not to bullet this paper.

    Article  PubMed  CAS  Google Scholar 

  8. Oudart H, Malan A, Maho Y, et al.: Day-night pattern of energy expenditure and body temperature in cachectic tumorbearing rats. Br J Cancer 2000, 83:1055–1060.

    Article  PubMed  CAS  Google Scholar 

  9. Hyltander A, Drott C, Korner V, et al.: Elevated energy expenditure in cancer patients with solid tumors. Eur J Cancer 1991, 27A:9–15.

    Google Scholar 

  10. Hyltander A, Korner U, Lunholm K: Evaluation of mechanisms behind elevated energy expenditure in cancer patients with solid tumor. Eur J Clin Invest 1993, 23:46–52.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    PubMed  CAS  Google Scholar 

  12. Salaman C: Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. Nutrition 2000, 16:1009–1012.

    Article  Google Scholar 

  13. Dunlop R, Campbell C: Cytokines and advanced cancer. J Pain Symptom Manage 2000, 20:214–232. This is an outstanding review of the association of cytokines with symptoms of advanced cancer. This review should be read by all who care for advanced cancer patients.

    Article  PubMed  CAS  Google Scholar 

  14. Tisdale M: Protein loss in cancer cachexia. Science 2000, 20:214–232. This is the best review of proteolysis that I have come across. The figure that Tisdale has included with the text is well worth reviewing.

    Google Scholar 

  15. Tisdale M: Metabolic abnormalities in cachexia and anorexia. Nutrition 2000, 16:1013–1014.

    Article  PubMed  CAS  Google Scholar 

  16. Tisdale M: Cancer anorexia and cachexia. Nutrition 2001, 17:438–442.

    Article  PubMed  CAS  Google Scholar 

  17. Bossola M, Muscaritoli M, Bellantone R, et al.: Serum tumor necrosis factor-alpha levels in cancer patients are discontinuous and correlate with weight loss. Eur J Clin Invest 2000, 30:1107–1112.

    Article  PubMed  CAS  Google Scholar 

  18. Konsman J, Dantzer R: How the immune and nervous systems interact during disease associated anorexia. Nutrition 2001, 17:664–668. This is the most detailed review of the pathophysiology of anorexia.

    Article  PubMed  CAS  Google Scholar 

  19. Brown D, Berkowitz D, Breslow M: Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer. J Clin Endocrinol Metab 2001, 86:162–166.

    Article  PubMed  CAS  Google Scholar 

  20. Arpaci F, Yilmaz I, Ozet A, et al.: Serum leptin level in colon cancer patients without significant weight loss [abstract]. Proc ASCO 2001, 20:405a.

    Google Scholar 

  21. Mantovani G, Maccio A, Mura L, et al.: Serum levels of leptin and proinflammatory cytokines in patients with advancedstage cancer at different sites. J Mol Med 2000, 78:554–561.

    Article  PubMed  CAS  Google Scholar 

  22. Asakawa A, Inui A, Kaga T, et al.: Ghrelin is an appetite stimulatory signal from stomach with structural resemblence to motlin. Gastroenterology 2001, 120:337–345.

    Article  PubMed  CAS  Google Scholar 

  23. Inui A: Cancer anorexia-cachexia syndrome: are neuropeptides the key? Cancer Res 1999, 59:4493–4501.

    PubMed  CAS  Google Scholar 

  24. Wang W, Lonnroth C, Svandberg E, et al.: Cytokine and cyclooxygenase-2 protein in brain areas of tumor-bearing mice with prostanoid-related anorexia. Cancer Res 2001, 61:4707–4715.

    PubMed  CAS  Google Scholar 

  25. King P, Widdowson P, Doods H, et al.: Effect of cytokines on hypothalamic neuropeptide Y release in vitro. Peptides 2000, 21:143–146.

    Article  PubMed  CAS  Google Scholar 

  26. Marks D, Ling N, Cone R: Role of the central melanocortin system in cachexia. Cancer Res 2001, 61:1432–1438.

    PubMed  CAS  Google Scholar 

  27. Leeuwen S, Berg J, Wattimens D, et al.: Lipolysis and lipid oxidation in weight losing cancer patients and healthy subjects. Metabolism 2000, 49:931–936.

    Article  Google Scholar 

  28. Tsujimoto S, Kawamura I, Inami M, et al.: Cachexia induction by EL-4 lymphoma in mice and possible involvement of impaired lipoprotein lipase activity. Anticancer Res 2000, 20:3111–3116.

    PubMed  CAS  Google Scholar 

  29. Finck B, Johnson R: Tumor necrosis factor-x regulates secretion of the adipocyte-derived cytokine, leptin. Microsc Res Tech 2000, 50:209–215.

    Article  PubMed  CAS  Google Scholar 

  30. Baracos V: Regulation of skeletal muscle protein turnover in cancer-associated cachexia. Nutrition 2000, 16:1015–1018. This review of proteolysis provides an excellent table of factors implicated in the regulation of muscle-protein turnover. It also provides background information to help the reader understand the rationale for using anabolic agents, omega-3 fatty acids, NSAIDs and anticytokines.

    Article  PubMed  CAS  Google Scholar 

  31. Lorite M, Smith H, Arnold J, et al.: Activation of ATPubiquintin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by proteolysis-inducing factor (PIF). Br J Cancer 2001, 85:297–302.

    Article  PubMed  CAS  Google Scholar 

  32. Costelli P, Tullio R, Baccino F, et al.: Activation of Ca+2-dependent proteolysis in skeletal muscle and heart in cancer cachexia. Br J Cancer 2001, 84:946–950.

    Article  PubMed  CAS  Google Scholar 

  33. Lazarus D, Destree A, Mazzola L, et al.: A model of cancer cachexia: contribution of the ubiquitin-proteasome pathway. Am J Physiol 1999, 277:E332-E341.

    PubMed  CAS  Google Scholar 

  34. Belizaro J, Lorite M, Tisdale M: Cleavage of caspases-1,-3,-6,-8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia. Br J Cancer 2001, 84:1135–1140.

    Article  Google Scholar 

  35. Royen M, Carbo N, Busquets S, et al.: DNA fragmentation occurs in skeletal muscle during tumor growth: a link with cancer cachexia? Biochem Biophys Res Commun 2000, 270:533–537.

    Article  PubMed  CAS  Google Scholar 

  36. Bossola M, Muscaritoli M, Costelli P, et al.: Increased muscle ubiquintin MRNA levels in gastric cancer patients. Am J Physiol Regul Integr Comp Physiol 2001, 280:R1518-R1523.

    PubMed  CAS  Google Scholar 

  37. Whitehouse A, Smith H, Drake T, et al.: Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res 2001, 61:3604–3609.

    PubMed  CAS  Google Scholar 

  38. Samuels S, Knowles A, Tilignac T, et al.: Protein metabolism in the small intestine during cancer cachexia and chemotherapy in mice. Cancer Res 2000, 60:4968–4974.

    PubMed  CAS  Google Scholar 

  39. Samuels S, Knowles A, Tilignac T, et al.: Higher skeletal muscle protein synthesis and lower breakdown after chemotherapy in cachectic mice. Am J Physiol Regul Integr Comp Physiol 2001, 281:R133-R139.

    PubMed  CAS  Google Scholar 

  40. O’Riordain M, Falconer J, Maingay J, et al.: Peripheral blood cells from weight-losing cancer patients control the hepatic acute phase response by a primarily interleukin-6 dependent mechanism. Int J Oncology 1999, 15:823–827.

    CAS  Google Scholar 

  41. Ikemoto S, Sugimura K, Yoshida N, et al.: TNF-alpha, IL-1B and IL-6 production by peripheral blood monocytes in patients with renal cell carcinoma. Anticancer Res 2000, 20:317–322.

    PubMed  CAS  Google Scholar 

  42. MacDonald N: Cachexia-anorexia workshop: introduction. Nutrition 2000, 16:1007–1008.

    Article  Google Scholar 

  43. Mantovani G, Maccio A, Massa E, et al.: Managing cancer related anorexia/cachexia. Drugs 2001, 61:499–514. The authors’ review of anorexia and cachexia is the best one published in 2001. This should be read by oncologists and palliative specialists.

    Article  PubMed  CAS  Google Scholar 

  44. Astrup A, Bulow J, Christensen N, et al.: Facultative thermogenesis induced by carbohydrate: a skeletal muscle component mediated by epinephrine. Am J Physiol 1986, 250:E226-E229.

    PubMed  CAS  Google Scholar 

  45. Astrup A, Simonsen L, Bulow J, et al.: Epinephrine mediates faculatitive carbohydrate-induced thermogenesis in human skeletal muscle. Am J Physiol 1989, 257:E340-E345.

    PubMed  CAS  Google Scholar 

  46. Hyltander A, Daneryd P, Sanstrom R, et al.: Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients. Eur J Cancer 2000, 36:330–334.

    Article  PubMed  CAS  Google Scholar 

  47. Cahlin C, Korner A, Axelsson H, et al.: Experimental cancer cachexia: the role of host derived cytokines interleukin (IL)-6 IL-12, interferon-gamma, and tumor necrosis factor of evaluated in gene knockout, tumor bearing mice on C57 BI background and eicosanoid-dependent cachexia. Cancer Res 2000, 60:5488–5493.

    PubMed  CAS  Google Scholar 

  48. Lundholm K, Gehlin J, Hyltander A, et al.: Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res 1994, 54:5602–5606.

    PubMed  CAS  Google Scholar 

  49. Wigmore S, Falconer J, Plester C, et al.: Ibuprofen reduces energy expenditures and acute phase protein production compared with placebo in pancreatic cancer patients. Br J Cancer 1995, 72:185–188.

    PubMed  CAS  Google Scholar 

  50. Barber M, Ross J, Fearon K: Disordered metabolic response with cancer and its management. World J Surg 2000, 24:681–689.

    Article  PubMed  CAS  Google Scholar 

  51. Cahlin G, Gelin J, Delbro D, et al.: Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related prostanoids. Cancer Res 2000, 60:1742–1749.

    PubMed  CAS  Google Scholar 

  52. Lonnroth C, Andersson M, Lundholm K: Indomethacin and telomerase activity in tumor growth retardation. Int J Oncology 2001, 18:929–937.

    CAS  Google Scholar 

  53. Mantovani G, Maccio A, Madeddu C, et al.: Immunotherapy (recombinant interleukin 2) hormone therapy (medoxyprogesterone acetate) and antioxidant agents as combined maintenance treatment of responders to previous chemotherapy. Int J Oncol 2001, 18:383–391.

    PubMed  CAS  Google Scholar 

  54. Maltoni M, Nanni O, Scarpi E, et al.: High-dose progestins for the treatment of cancer anorexia syndrome: a systematic review of randomized clinical trials. Ann Oncol 2001, 12:289–300. Systematic reviews of randomized clinical trials for symptom management are rare. These authors have nicely demonstrated in a convincing manner the benefits of progesterone in the management of anorexia.

    Article  PubMed  CAS  Google Scholar 

  55. D’Olimpio J: Contemporary drug therapy in palliative care: new directions. Cancer Invest 2001, 19:413–423.

    Article  PubMed  CAS  Google Scholar 

  56. Nelson K, Walsh D, Deeter P, et al.: A phase II study of delta-nine-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care 1994, 10:89–97.

    Google Scholar 

  57. Gorter R: Cancer cachexia and cannabinoids. Forschende Komplementar Medizin 1999, 6(suppl 3):21–22.

    Article  Google Scholar 

  58. Jatoi A, Windschitl H, Loprinzi C, et al.: Dronabinol versus megestrol acetate versus both for cancer-associated anorexia: a North Central Cancer Treatment Group Study [abstract]. Proc ASCO 2001, 20:388a.

    Google Scholar 

  59. Bozzetti F, Gavazzi C, Ferrari P, et al.: Effect of total parenteral nutrition on the protein kinetics of patients with cancer cachexia. Tumori 2000, 86:408–411.

    PubMed  CAS  Google Scholar 

  60. Tayek J, Brasel J: Failure of anabolism in malnourished cancer patients receiving growth hormone: a clinical research center study. J Clin Endocrinol Metab 1995, 80:2082–2087.

    Article  PubMed  CAS  Google Scholar 

  61. Wang W, Iresjo B, Karlsson L, et al.: Provision of rhIGF-I/ IGFBP-3 complex, attenuated development of cancer cachexia in an experimental tumor model. Clin Nutr 2000, 19:127–132.

    Article  PubMed  CAS  Google Scholar 

  62. Suanderg E, Ohlsson C, Kimball S, et al.: rhIGF/IGFBP-3 complex, but not free rhIGF-I, supports muscle protein bio-sythesis in rats during semistarvation. Eur J Clin Invest 2000, 30:438–446.

    Article  Google Scholar 

  63. Herrera N, Zimmerman A, Dykstra D, et al.: Clebuterol in the prevention of muscle atrophy: a study of hindlimbunweighted rats. Arch Phys Med Rehabil 2001, 82:930–934.

    Article  PubMed  Google Scholar 

  64. Izeboud C, Monshouwer M, van Miert A, et al.: The betaadrenoreceptor agonist clenbuterol is a potent inhibitor of the LPS-induced production of TNF-alpha and IL-6 in vitro and in vivo. Inflamm Res 1999, 48:497–502.

    Article  PubMed  CAS  Google Scholar 

  65. Yoshimura T: Modulation of cytokine production from human mononuclear cells by several agents. Yakugaku Zasshi 2000, 120:1227–1290.

    Google Scholar 

  66. Hyltander A, Svaninger G, Lundholm K: The effect of clenbuterol on body composition in spontaneously eating tumour bearing mice. Biosci Rep 1993, 13:325–331.

    Article  PubMed  CAS  Google Scholar 

  67. Hussey H, Tisdale M: Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentenoic acid. Br J Cancer 1999, 80:1231–1235.

    Article  PubMed  CAS  Google Scholar 

  68. Whitehouse A, Tisdale M: Downregulation of ubiquitindependent proteolysis by eicosapentaenoic acid in acute starvation. Biochem Biophys Res Commun 2001, 285:598–602.

    Article  PubMed  CAS  Google Scholar 

  69. Diggle C, Pitt E, Roberts P, et al.: N;-3 and N;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of P-53 gene function. J Lipid Res 2000, 41:1509–1515.

    PubMed  CAS  Google Scholar 

  70. Gogos C, Skoutelis A, Kalfarentzos F, et al.: The effects of lipids on the immune response of patients with cancer. J Nutr Health Aging 2000, 4:172–175.

    PubMed  CAS  Google Scholar 

  71. Kontogiannea M, Gupta A, Ntanios F, et al.: Omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells. J Surg Res 2000, 92:201–205.

    Article  PubMed  CAS  Google Scholar 

  72. Murota S, Onodera M, Morita I: Regulation of angiogenesis by controlling VEGF receptor. Ann N Y Acad Sci 2000, 902:208–212.

    Article  PubMed  CAS  Google Scholar 

  73. Mirnikjoo B, Brown S, Kim H, et al.: Protein kinase inhibition by omega-3 fatty acids. J Biol Chem 2001, 276:10888–10896.

    Article  PubMed  CAS  Google Scholar 

  74. Yam D, Peled A, Skinitzky M, et al.: Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. Cancer Chemother Pharmacol 2001, 47:34–40.

    Article  PubMed  CAS  Google Scholar 

  75. Wigmore S, Ross J, Falconer J, et al.: The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition 1996, 1(suppl 12):527–530.

    Google Scholar 

  76. Wigmore S, Fearon K, Maingay J, et al.: Down-regulation of the acute phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin-6. Clin Sci 1997, 92:215–221.

    PubMed  CAS  Google Scholar 

  77. Burns C, Halabi S, Ciamon G, et al.: Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia. Cancer and Leukemia Group B study 9473. Clin Cancer Res 1999, 5:3942–3947.

    PubMed  CAS  Google Scholar 

  78. Barber M, Fearon K: Tolerance and incorporation of a highdose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia. Lipids 2001, 36:347–351. Dose tolerance studies hopefully will lead to randomized trials of eicosapentanoic acid within the cooperative oncology group structure. CALG-B has done the same [77]. We hope to see a trial initiated soon.

    Article  PubMed  CAS  Google Scholar 

  79. Gogos C, Ginopoulo S, 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. Cancer 1998, 82:395–402.

    Article  PubMed  CAS  Google Scholar 

  80. Lissoni P, Barni S, Tancini G, et al.: Role of the pineal gland in the control of macrophage functions and its possible implication in cancer: a study of interactions between tumor necrosis factor-alpha and the pineal hormone melatonin. J Biol Regul Homeost Agents 1994, 8:126–129.

    PubMed  CAS  Google Scholar 

  81. Lissoni P, Paolorossi F, Tancini G, et al.: Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 1996, 32A:1340–1343.

    Article  PubMed  CAS  Google Scholar 

  82. Futagmi M, Satos S, Sakamoto T, et al.: Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP) sensitivity of cultured human ovarian cancer cells. Gynecol Oncol 2001, 82:544–549.

    Article  CAS  Google Scholar 

  83. Kanishi Y, Kobayashi Y, Noda S, et al.: Differential growth inhibitory effect of melatonin on two endometrial cancer cell lines. J Pineal Res 2000, 28:227–233.

    Article  PubMed  CAS  Google Scholar 

  84. Lissoni P, Bolis S, Brivio F, et al.: A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus pineal hormone melatonin in untreatable advanced hematologic malignancies. Anticancer Res 2000, 20:2103–2105.

    PubMed  CAS  Google Scholar 

  85. Bartsch C, Bartsch H: Significance of melatonin in malignant diseases. Wein Klin Wochenschr 1997, 109:722–729.

    CAS  Google Scholar 

  86. Panzer A, Viljoen M: The validity of melatonin as an oncostatic agent. J Pineal Res 1997, 22:184–202. Melatonin is more that an agent to use in order to avoid jet lag. This review nicely outlines its multiple benefits in advanced cancer. A standard preparation needs to be developed because the over-thecounter products are not regulated in the United States. Dose tolerance and dose response studies are needed.

    Article  PubMed  CAS  Google Scholar 

  87. Bartsch C, Bartsch H: Melatonin in cancer patients and in tumor-bearing animals. Adv Exp Med Biol 1999, 467:247–264.

    PubMed  CAS  Google Scholar 

  88. Lissoni P, Barni S, Mandala M, et al.: Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumor patients with poor clinical status. Eur J Cancer 1999, 35:1688–1692. Melatonin has been an interest of these authors. This study suggests that melatonin reduces chemotherapy toxicity and improves efficacy. Larger controlled prospective trials are needed.

    Article  PubMed  CAS  Google Scholar 

  89. Lissoni P, Paolorossi F, Ardizzola A: A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res 1997, 23:15–19.

    Article  PubMed  CAS  Google Scholar 

  90. DeMuro R, Mafziger A, Blask D: The absolute bioavailability of oral melatonin. J Clin Pharmacology 2000, 40:781–784.

    Article  CAS  Google Scholar 

  91. Radomsky C, Levine N: Thalidomide. Dermatol Clin 2001, 19:87–103.

    PubMed  CAS  Google Scholar 

  92. Richardson P, Hideshima T, Anderson K: Thalidomide: the revival of a drug with therapeutic promise in the treatment of cancer. Prin Pract Oncol 2001, 15:1–10.

    Google Scholar 

  93. Peuckmann V, Fisch M, Bruera E: Potential novel uses of thalidomide, focus on palliative care. Drugs 2000, 60:273–292. These authors have extensively reviewed the palliative benefits of thalidomide, as well as its mechanisms of action and toxicities. This is an agent we will see used for both its antitumor activity and its palliative benefit.

    Article  PubMed  CAS  Google Scholar 

  94. Keifer K, Guttridge D, Ashburner B, et al.: Inhibition of NF-kappaB activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem 2001, 276:2382–2387.

    Article  Google Scholar 

  95. Boasberg P, O’Day S, Weisberg M, et al.: Thalidomide induced cessation of weight loss and improved sleep in advanced cancer patients with cachexia [abstract]. Proc ASCO 2000, 19:609A.

    Google Scholar 

  96. Bruera E, Neumann C, Pituskin E, et al.: Thalidomide in patients with cachexia due to terminal cancer: preliminary report. Ann Oncol 1999, 10:857–859.

    Article  PubMed  CAS  Google Scholar 

  97. Adlard J: Thalidomide in the treatment of cancer. Anticancer Res 2000, 11:787–791.

    Article  CAS  Google Scholar 

  98. Thomas D, Kantarjian H: Current role of thalidomide in cancer treatment. Curr Opin Oncol 2000, 12:564–573.

    Article  PubMed  CAS  Google Scholar 

  99. Rajkumar S, Kyle R: Thalidomide in the treatment of plasma cell malignancies. J Clin Oncol 2001, 19:3593–3595.

    PubMed  CAS  Google Scholar 

  100. Little R, Wyvill K, Pluda J, et al.: Activity of thalidomide in AIDS-related Kaposi’s sarcoma. J Clin Oncol 2000, 18:2593–2602.

    PubMed  CAS  Google Scholar 

  101. Hao S, Avraham Y, Mechoulam R, et al.: Low dose anadamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 2000, 392:147–156.

    Article  PubMed  CAS  Google Scholar 

  102. Kawamura I, Lacey E, Inami M, et al.: Ponalrestat an aldose reductase inhibitor, inhibits cachexia syndrome in nude mice bearing human melanomas F361 and SEKI. Anticancer Res 1999, 19:4091–4098.

    PubMed  CAS  Google Scholar 

  103. Kawamura I, Lacey E, Yammamoto N, et al.: Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon 26 adenocarcinoma in mice. Anticancer Res 1999, 19:4105–4112.

    PubMed  CAS  Google Scholar 

  104. Agteresch H, Dagnelie P, Gasst A, et al.: Randomized clinical trial of adenosince 5′-triphosphate in patients with advanced non-small cell lung cancer. J Natl Cancer Inst 2000, 92:321–328.

    Article  PubMed  CAS  Google Scholar 

  105. Ishiko O, Sumi T, Yoshida H, et al.: Effect of cyclic plasma perfusion on apoptosis regulatory proteins in primary tumors of VX2-carcinoma-bearing rabbits. Intervent J Oncol 2001, 19:325–329.

    CAS  Google Scholar 

  106. Ishiko O, Sumi T, Yoshida H, et al.: Anemia-inducing substance is related to elimination of lipolytic hyeractivity by cyclic plasma perfusion in human cancer cachexia. Nutr Cancer 2000, 37:169–172.

    Article  PubMed  CAS  Google Scholar 

  107. Josephs M, Solorzano C, Taylor M, et al.: Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-Ira. Am J Physiol Regul Integr Comp Physiol 2000, 278:R824-R830.

    PubMed  CAS  Google Scholar 

  108. Lopez-Soriano J, Costello P, Busquets S, et al.: Interleukin-15 antagonizes muscle protein waste in tumor-bearing rats. Br J Cancer 2000, 83:526–531.

    Article  PubMed  Google Scholar 

  109. Schwartz S, Hernandez A, Evers B: The role of NF-kappa B/I kappa B proteins in cancer: implications for novel treatment strategies. Surg Oncol 1999, 8:143–153.

    Article  PubMed  CAS  Google Scholar 

  110. Kawamura I, Morishita R, Tomita N, et al.: Intratumoral injection of oligonucleotides to the NFkappaB binding site inhibits cachexia in a mourse tumor model. Gene Ther 1999, 6:91–97.

    Article  PubMed  CAS  Google Scholar 

  111. Nukatsuka M, Fujioka A, Saito H, et al.: Prolongation of survival period and improvement of cancer cachexia by longterm administration of UFT. Cancer Lett 1996, 104:197–203.

    Article  PubMed  CAS  Google Scholar 

  112. Eda H, Tanaka Y, Ishitsuka H: 5′deoxy-5-flurouridine improves cachexia by a mechanism independent of it antiproliferative action in colon 26 adenocarcinoma-bearing mice. Cancer Chemother Pharmacol 1991, 29:1–6.

    Article  PubMed  CAS  Google Scholar 

  113. Numico G, Russi E, Merlano M: Best supportive care in non-small cell lung cancer: is there a role for radiotherapy and chemotherapy? Lung Cancer 2001, 32:213–226.

    Article  PubMed  CAS  Google Scholar 

  114. MacDonald N: Cachexia-anorexia workshop summary and conclusions. Nutrition 2000, 16:1019–1020. The entire workshop MacDonald summarizes is worth reviewing. The author reviews important questions that should direct research efforts in anorexia and cachexia.

    Article  Google Scholar 

  115. Pichard C, Ursula K: Body composition measurements during wasting disease. Current Opin Clin Nutr Metabol Care 1998, 1:357–361.

    Article  CAS  Google Scholar 

  116. Ribaudo J, Cella D, Hahn E, et al.: Re-evaluation and shortening of the functional assessment of anorexia/cachexia therapy (FAACT) questionnaire. Qual Life Res 2001, 9:1137–1146.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Harry R. Horvitz Center for Palliative Medicine, Taussig Cancer Center, The Cleveland Clinic Foundation, R35, 9500 Euclid Avenue, 44195, Cleveland, OH, USA

    Mellar P. Davis MD, FCCP

Authors
  1. Mellar P. Davis MD, FCCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davis, M.P. New drugs for the anorexia-cachexia syndrome. Curr Oncol Rep 4, 264–274 (2002). https://doi.org/10.1007/s11912-002-0025-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-002-0025-z

Keywords

Search

Navigation