From *Geriatric division, Department of Medicine, 79 Middleville Road, VAMC at Northport, New York 11768-2290. * Shing-shing Yeh Ph.D., MD, Box 111, VAMC Northport, 79 Middleville Road, NORTHPORT, NY 11768; Fax-#: (631) 754-7964, e-mail: Shing-shing.Yeh @med.VA.GOV * Dr. Shing-shing Yeh, Department of Medicine, VA Medical Center Northport, 79 Middleville Road Northport, New York 11768-2290; ** Ms Suh-Yuh Wu, Department of Preventive Medicine, SUNY Medical Center at Stony Brook, Stony Brook, NY 11794; *** Daniel M. Levine, Thomas S Parker, The Rogosin Institute, 505 E. 70th Street, New York, NY 10021; **** Drs. Jeffery S. Olson and Michael R. Stevens, Oncology /Immunology Division, Bristol-Myers Squibb Company, Princeton, New Jersey; ***** Dr. Michael W. Schuster, the Weill Medical College of Cornell University and the New York Presbyterian Hospital, Division of Hematology/Oncology, 520 East 70th Street, Baker 16, New York, NY 10021. Grant Support: By unrestricted research grants from Bristol-Myers Squibb Company.

Abstract: Background. The geriatric wasting syndrome (GWS) has been associated with proinflammatory cytokines, depression and progressive decline in quality of life (QOL). The objective of this study was to evaluate the correlation between the changes in cytokine levels and appetite, nutritional markers, and QOL in geriatric patients with GWS following a randomized clinical trial of megestrol acetate (MA) versus placebo. Methods. This was a prospective, double-blind, placebo-controlled trial. We evaluated 69 predominantly male (3 females) nursing home residents with weight loss of =5% of their usual body weight over the past three months or body weight 20% below their ideal body weight. Patients were randomly assigned to receive either placebo or megestrol acetate (MA) oral suspension (O.S.) 800 mg/day for 12 weeks and were then followed for 13 weeks off treatment. Data on appetite, weight, nutritional status, QOL and cytokine levels were collected at baseline and week 12. The correlation between appetite, weight, nutritional status, sense of well being and cytokine level changes in response to MA treatment was examined at week 12. Results. Appetite, sense of well being, and QOL assessed by an "enjoyment list" significantly improved in the MA arm. Rising prealbumin showed a negative correlation with decreasing IL-6 (r = -0.51), TNFR-p 55 (r = -0.49) and sIL-2R (r = -0.38). There was also an improvement in prealbumin and a decrease in IL-6 and TNFR-p55 in the MA-arm (p < 0.01). A correlation between a decrease in the IL-6 levels and improvement in depression (r = 0.50) was seen in the MA arm as well. Improvement in appetite positively correlated with increased enjoyment of life (r = -0.41), less depression (r = -0.34), improved sense of well being (r = 0.36), prealbumin gain (r = 0.30), and weight gain (r = 0.38) by 12 weeks. Also, improvement in appetite positively correlated with improvement in nutritional parameters such as prealbumin, albumin, fat free mass and weight in the MA arm. Conclusions. In a geriatric nursing home population with weight loss, reduction in cytokine levels after MA treatment correlates with improvement in appetite, prealbumin, albumin, and improvement in quality of life.

Key words: Nutrition, appetite, pro-inflammatory cytokines, megestrol acetate, aging, nursing home, elderly, quality of life, nutritional status