Megestrol acetate as a biomodulator

Megestrol acetate is a synthetic analog of progesterone. In general, megestrol acetate exerts its progesterone-like hormonal effect by binding to the progesterone receptor. It has been recognized that megestrol acetate can increase weight and improve some aspects of quality of life in cancer patients and in patients with the acquired immunodeficiency syndrome. This effect occurs in patients with or without concurrent chemotherapy or radiotherapy, through an as yet unknown mechanism. Recently, megestrol acetate has been shown to reverse, at least partially, multidrug resistance to doxorubicin and/or vincristine in cancer cell lines. This potentially beneficial effect has not yet been studied in clinical trials. This biological activity is thought to be mediated through the unique binding of megestrol acetate to p-glycoprotein. At least in vitro megestrol acetate can also enhance the cytotoxic effect of these two chemotherapeutic agents in some MDR-nonexpressing cell lines. These findings suggest that megestrol acetate deserves further preclinical and clinical studies to evaluate its potential role of enhancing cytotoxicity of chemotherapy and improving the quality of life of cancer patients.