1. Management of cancer cachexia

2. Cancer cachexia Anorexia, chronic nausea, asthenia, psychological stress. Poor survival and decreased tolerance to both radiotherapy and chemotherapy. No evidence : nutritional or pharmacological intervention improve survival. Exception : GI obstruction from malignancy. Lancet Oncolo 2000;1:138-47

3. Goals Ideal : reverse syndrome completely  eliminate tumor mass  impossible Reasonable :  Improving general comfort.  Relieving of symptoms : anorexia, nausea, asthenia.  Improve level of functioning. Lancet Oncolo 2000;1:138-47

4. Management approach Nutrition Pharmacological intervention Psychological and behavioral therapy Lancet Oncolo 2000;1:138-47

5. Nutrition Nutritional counseling improve the daily caloric intake. Maximize oral intake by allowing the patient flexibility in type, quantity and timing if meals. Disease progresses  decrease nutritional support. Adequate mouth care and small amount of ice chips or sips of cold beverages may be adequate In dehydration : use hypodermoclysis Lancet Oncolo 2000;1:138-47

6. ESPEN guideline 2006

7. Hypodermoclysis A family member can do hypodermoclysis at home after one lesson from the doctor Using hypodermoclysis, a family member can give the sick person about 90 ounces of fluid a day by giving 45 ounces of fluid in two different places. American Family Physician Nov 1,2001

8. Pharmacological interventions Main purpose :  Anorexia  Chronic nausea Not affect psychological distress from a negative body image : no weight gain. Lancet Oncolo 2000;1:138-47

9. Pharmacological interventions Proven efficacy  Corticosteroid  Progesterone  Metoclopramide No proven efficacy  Cyproheptadine  Hydrazine sulphate  Thalidomide  Melatonin  B2-agonist  Anabolic steroid  GH  Cannabinoid  NSAIDs  Eicosapentanoic acid(EPA)  Branched chain amino acid Lancet Oncolo 2000;1:138-47

10. CA Cancer J Clin 2002;52:72-91

11. Corticosteroid Mechanism  Inhibition of synthesis and/or release of proinflammatory cytokines (TNF-α,IL-1), anorexigenic mediators(leptin, CRF, serotonin)  Enhance NPY levels in hypothalamus. X X Lancet Oncolo 2000;1:138-47

12. Corticosteroid Improving appetite, food intake, sensation of well-being, performance status. No significant weight gain. Dose : 20-40 mg of prednisolone Risk : peptic ulcer, etc. Lancet Oncolo 2000;1:138-47

13. Progesterone Mechanism  Stimulate NPY in the hypothalamus  Modulation of Ca channel in VMH(satiety center)  Inhibition of proinflammatory cytokines X X Lancet Oncolo 2000;1:138-47

14. Progesterone Improve appetite, caloric intake, sensation of well- being. Significant weight gain (mostly fat). Dose : megestrol acetate 160-1600 mg, optimum dose : 800 mg Response can be seen in 1 week. Risk : thromboembolism, breakthrough bleeding, peripheral edema, hyperglycemia, hypertension, Cushing syndrome, alopecia, adrenal insufficiency. Lancet Oncolo 2000;1:138-47

15. Metoclopramide Mechanism  Antidopaminergic drug  Central antiemetic  Gastroprokinetic : improve gastric emptying X X Lancet Oncolo 2000;1:138-47

16. Metoclopramide Improve in appetite, food intake. Dose : 10 mg before meals and bedtime. Risk : minimal Lancet Oncolo 2000;1:138-47

17. Cyproheptadine Mechanism  Antiserotoninergic RCT  mild increase appetite, food intake.  No weight gain. Risk : sedation X Lancet Oncolo 2000;1:138-47

18. Hydrazine sulphate Mechanism  Inhibit gluconeogenesis Pilot study  improve appetite and nutritional status.  No weight gain. Substantial side effects and deterioration of QOL scales X Lancet Oncolo 2000;1:138-47

19. Thalidomide Mechanism  Inhibit production of TNF-α Pilot study  Improve appetitie, well- being, nausea, insomnia X Lancet Oncolo 2000;1:138-47

20. Melatonin Mechanism  Decrease circulating concentration of TNF-α Preliminary studies  Weight loss > 10% fewer than best supportive care X Lancet Oncolo 2000;1:138-47

21. Beta-adrenoreceptor agonist Clenbuterol Mechanism  Decrease protein catabolism. Positive effect on muscle mass in tumor- bearing rats. Risk : nervousness, tachycardia, tremor, headache. X Lancet Oncolo 2000;1:138-47

22. Anabolic steroid Mechanism  Decrease protein catabolism RCT  Less effective than dexamethasone/megest rol acetate in appetite and nutritional variables. X Lancet Oncolo 2000;1:138-47

23. Growth hormone Mechanism  Stimulate muscle protein synthesis. No trial in cancer cachexia. X Lancet Oncolo 2000;1:138-47

24. Cannabinoid Mechanism  Stimulate appetite No trial in cancer cachexia. Risk : somnolence, confusion, perceptual disturbance. X Lancet Oncolo 2000;1:138-47

25. NSAIDs Mechanism  Inhibit the production of cytokine  Stimulate appetite Preliminary studies : Ibuprofen  Weight gain  Decrease production of CRP X X Lancet Oncolo 2000;1:138-47

26. EPA(Eicosapentanoic acid) Omega 3 fatty acid Mechanism  Inhibition of lipolysis and muscle protein degradation  Eicosapentanoic acid decrease production of IL-6 RCT : controversy in efficacy X X X Lancet Oncolo 2000;1:138-47

27. Psychological and behavioral therapy Multidisciplinary approach  Oncologist  Nurses  Dieticians  Patient and family Secondary depression. Relaxation, hypnosis, group psychotherapy. Lancet Oncolo 2000;1:138-47

28. Thank you