Mifepristone May Be the Best Single Pharmaceutical Agent for Treatment of a Variety of Advanced Cancers

Abstract

Rationale: To provide evidence to support the provocative statement that the progesterone receptor modulator (antagonist) mifepristone may be the best single anticancer drug to use for advanced metastatic cancer. Objective: A summary of cancer cell line studies, controlled treatment trials of several types of spontaneous murine cancers, and anecdotal human case reports that support the premise of this review, is provided. The concept suggests that the mechanism of action involves the suppression of an immunosuppressive protein called the progesterone induced blocking factor (PIBF) that requires stimulation of a membrane progesterone receptor for its production. Findings: Cell line studies show that mifepristone can down-regulate PIBF production by many different leukemia cell lines and inhibit proliferation of cancer cell lines, e.g., ovarian cancer and glioblastoma multiform stage IV. Controlled murine studies found improved longevity and quality of life as monitored by body conditioning scores following oral gavage of mifepristone including leukemia, lung, testicular, and prostate cancer. Most importantly, mifepristone anecdotally has been found to provide extension of life and improved quality of life in patients with a large majority of advanced cancers that were no longer responding to any available anticancer drug options. These cancers include colon, kidney, small cell and non- mall cell lung, pancreatic, thymic epithelial cell, transitional cell of the renal pelvis, grade IV glioblastoma multiform, fibrous osteogenic sarcoma, and leiomyosarcoma cancers. Of note, the majority of the cancers treated are not known to be associated with the presence of classical nuclear progesterone receptor. Conclusions: Related to additional benefits of easy oral administration, low cost, low risk of short-term side effects, or immediate, severe, or delayed severe complications, and its efficacy despite starting it, in general, in late stages of advanced metastatic disease in patients previously treated with standard or experimental drugs, and its beneficial effects in a large variety of cancers, mifepristone may be the best single agent anticancer drug for the treatment of advanced cancers.