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Thalidomide + megestrol acetate is an oral combination therapy investigated primarily for the management of cancer-related anorexia/cachexia syndrome (CACS). Thalidomide is an immunomodulatory and anti-inflammatory agent that inhibits pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), suppresses nuclear factor kappa B (NF-κB), and has antiangiogenic properties. Megestrol acetate is a synthetic progestin with appetite-stimulating, antineoplastic, and anti-cachectic effects, commonly used to treat anorexia and cachexia in cancer or AIDS patients. Clinical studies have shown that the combination of these two agents results in greater improvements in body weight, appetite, quality of life, grip strength, fatigue reduction, inflammatory markers (IL-6 and TNF-α), performance status scores, and other cachexia-related endpoints compared to megestrol acetate alone. Toxicity with this regimen has generally been reported as minimal[1][3][5].
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