Abstract 3587: Evidence that membrane progesterone receptors (mPR) play a key role in cancer metastases in most cases of metastatic cancer

Abstract

Abstract An immunomodulatory protein called the progesterone induced blocking factor (PIBF) is essential for the fetal semi-allograft to escape immune surveillance. Many cancer cell lines make both mPRs for PIBF and the protein itself. The progesterone receptor (PR) antagonist mifepristone added to cancer cell line cultures down-regulated mRNA for PIBF and the PIBF protein. This IRB approved study (that required a compassionate use IND from the FDA) evaluated oral mifepristone 200mg per day (majority) or 300mg in patients with very advanced cancers with no more treatment options available. Patients would remain under the care of their primary oncologists (FDA requirement). Because the nuclear (n) PR may be protective against cancer spread, only patients with cancers negative for the nPR were treated. Patients with the following types of cancers received mifepristone: non-small cell lung cancer (NSCLC) (n=9), small cell lung cancer (SCLC) (n=2), colon (n=3), pancreatic (n=2), thymic epithelial cell (n=1), transitional cell carcinoma of the renal pelvis (n=1), malignant fibrous histiocytoma (n=1), glioblastoma multiforme stage IV (n=1), leiomyosarcoma (n=1). All 21 patients showed significant palliative benefits, especially but not limited to, marked reduction in pain and marked improvement in energy, decreased dyspnea on exertion, and return of mental clarity. For those who had repeat CT evaluation no one failed to show shrinkage and decrease in malignant lesions and 2 (leiomyosarcoma and SCLC) showed complete remission after a few months on mifepristone. Five patients (3 females, 2 males) with SCLC (1), NSCL (n=3) and fibrous osteosarcoma (n=1) survived at least 5 years with 2 dying from cancer unrelated causes (SCLC and NSCLC). Two are still alive (NSCLC with EGFR mutation and brain metastases). The male with fibrous osteosarcoma died after stopping mifepristone in favor of a new drug recommended by his oncologist. Two patients lived over 2 years. Most would have lived longer had they not stopped mifepristone. Other observations: significant palliative benefits are seen within 3 weeks of taking mifepristone before any evidence of significant tumor regression. After a period of time, some lesions (especially in the primary location) may start growing slowly, but this is not a sign of loss of drug efficacy and long good quality life is still probable if one remains on the drug. The cancer spreads rapidly if one stops the mifepristone. The usual reason for stopping the drug was intervention by the primary oncologist suggesting a new clinical trial because there has not been complete remission of the cancer or some tumor growth (usually slow) or finances. Not one patient had a side effect. Hopefully this study will generate interest in treating patients with advanced cancer with mifepristone, especially those devoid of the nPR. These data support the role of mPRs in cancer proliferation. Citation Format: Jerome H. Check, Diane Check, Brooke Neumann, Carrie Wilson. Evidence that membrane progesterone receptors (mPR) play a key role in cancer metastases in most cases of metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3587.