**4. Clinical studies using mifepristone to treat cancer**

#### **4.1 Cancers positive for the classic progesterone nuclear receptor**

The presence of the classic nuclear P receptor in breast cancer tumors has been known for at least 40 years [26]. The thinking in those days was that the presence of the hormone receptor may be needed for the tumor to proliferate. Thus, intervening with the hormone receptor interaction may inhibit cancer growth while not creating serious adverse effects in the patient as long as the hormone-receptor interaction was not essential to life or well-being.

Based on the beneficial effects of blocking the estrogen receptor with selective estrogen receptors, that is, tamoxifen, it is not surprising that mifepristone was evaluated for treating advanced breast cancer with the thought that the interaction of progesterone with the classic nuclear progesterone receptor could somehow allow tumors, for example, breast and ovarian cancer to proliferate.

Mifepristone is a type II progesterone receptor antagonist which promotes DNA binding and also promotes progesterone receptor phosphorylation [46]. Mifepristone was given to advanced stage tamoxifen resistant women (second line setting) and the authors reported a complete or partial response in about 10% [47]. However, 6 of the 11 showed stable disease [47]. Another small study found an objective response rate of 18% [48]. For first line, mifepristone for untreated metastatic breast cancer, a 10% objective response rate was observed [49].

#### *Progesterone and Glucocorticoid Receptor Modulator Mifepristone (RU-486) as Treatment… DOI: http://dx.doi.org/10.5772/intechopen.93545*

The main method of evaluating efficacy of anticancer treatments 25–40 years ago, and even today, is inhibition of disease progression. Thus, the improvement did not seem adequate enough compared to other "more encouraging therapies". Thus, interest waned in treating advanced breast cancer with mifepristone. Subsequently, more experience with mifepristone therapy for a variety of advanced cancers will show that although sometimes the treatment will cause a very good objective remission, the majority of the time the drug provides significant palliation and extension of a higher quality life while it slows disease progression.

For ovarian cancer not only is the classic nuclear progesterone receptor present but it also predicts a favorable outcome [50]. For similar reasoning as with breast cancer, mifepristone was given about 20 years ago to patients with ovarian cancer who had persistent lesions or recurrent lesions despite one round of chemotherapy [51]. Mifepristone 200 mg/day was given daily and continued until disease progression was found. They were treated for a mean of only 2 months. For 34 patients there was a response in 26.5% (9% complete and 17.5% partial) [51]. A second study of this drug conducted 10 years later showed a partial response in 42% of patients [52]. Again, the drug was stopped if there was any evidence of progression. The median time of treatment was 2 months [52]. From what we know today, if they would have continued the drug, the ovarian cancer may have progressed slowly while the patient maintained a high-quality extension of life [53].
