22 However, overexpression of proinflammatory cytokines, such as interleukin (IL)-1, IL-6, tumor necrosis factor, or interferon-γ, as well as macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF-15) appear to be involved.23 and 24 Activation of these factors has effects on peripheral (lipolysis, proteolysis, insulin resistance) as well as on central

pathways (hypothalamic appetite regulation).23 and 25 Megestrol acetate, a synthetic, orally active derivative of the hormone progesterone, was originally synthesized in 1963 as a contraceptive drug.26 Beginning in 1967, it was used in the treatment of breast cancer. Beginning in 1993, it was approved in the United States and in several European countries for the treatment of the anorexia-cachexia www.selleckchem.com/PI3K.html syndrome.26 It has recently been argued that the use of megestrol acetate also may be helpful in patients with muscle wasting without weight loss.15 Wen et al27 recently studied 102 patients with cancer-related anorexia/cachexia syndrome who Panobinostat price were randomly

assigned to receive, for 8 weeks, either a combination therapy of oral megestrol acetate at a dosage of 160 mg twice daily plus oral thalidomide 50 mg twice daily or megestrol acetate 160 mg twice daily alone (all studies discussed in the text are summarized in Table 1). Patients in either group showed an increase in their appetite score (both P < .03). The increase in body weight and the improvement in quality of life were more pronounced in the group that received combination therapy than in the group on megestrol acetate alone. Serum values of IL-6 and tumour necrosis factor decreased only in the combination Tenoxicam therapy group, just as handgrip strength was only improved in this group. 27 Another small study 28 used a combination therapy of oral formoterol

(80 μg/d) and megestrol acetate tablets (480 mg/d) for up to 8 weeks in 13 patients with advanced malignancy and involuntary weight loss. Six of 7 patients who completed the study showed an improvement in muscle size and muscle function as assessed using quadriceps strength and magnetic resonance imaging. In fact, quadriceps volume increased significantly (P < .02); in addition, there was a trend toward an increase in the patients’ quadriceps and handgrip strength. 28 Just as with thalidomide, several workers have tried to enhance the effects of megestrol acetate on appetite using different approaches. L-carnitine, for example, plays a central role in fatty acid metabolism and possesses antioxidant and anti-inflammatory properties.29 Madeddu et al30 randomized 60 patients with advanced cancer at any site and weight loss of at least 5% to receive either L-carnitine 4 g per day plus celecoxib 300 mg per day or the same regimen plus megestrol acetate 320 mg per day.