Abstract 695: Treatment with oral mifepristone enables a patient with end-stage pancreatic cancer in hospice, on a morphine drip, to restore a decent quality of life

Abstract

Abstract The progesterone (P) receptor modulator, mifepristone, has been previously found to provide significant improvement in length and quality of life in people with a variety of advanced cancers. A 57 year old man with severe abdominal pain, dyspnea, nausea weakness and vomiting, in hospice with marked sedation from a morphine drip, was treated with oral mifepristone 200mg/day, as an option to extend his lifespan with reasonable quality of life. He had never received treatment for his disease and was given a prognosis of only 1-3 weeks to live, by his oncologist. He showed quick improvement in both his nausea (which was intractable), and his abdominal pain, within one month of treatment. His first visit he was wheelchair ridden, next visit he had progressed to a cane and after 2 months walked in without any assistance. He has now been on oral mifepristone 200mg/day for 5 months, as his only treatment. His only complaint is slight weakness and mild dyspnea; he is considered ECOG-2 when initially he was ECOG-IV. He has had no side effects from the mifepristone and rarely needs his previous analgesics, or anti-emetics. The hypothesized mechanism of action of this drug is to inhibit the activation of a membrane P receptor in the cancer cells that causes the production of a 757 amino acid unique protein measuring 90 kDa that is involved in cell-cell regulation, but is converted to smaller intracytoplasmic splice variants, which are immunosuppressive proteins. It is called the progesterone induced blocking factor (PIBF). When these smaller splice variants are released into the tumor micro-environment, they suppress cytolytic activity of the cellular immune system, e.g., by stabilizing perforin granules in natural killer cells. The fact that treatment with mifepristone has been shown to improve length and quality of life, not only in cancer associated with the classic nuclear P receptor, e.g., breast, ovarian, and endometrial cancer, but also those cancers devoid of the classic nuclear receptor, e.g., small cell and non-small cell lung cancer, leukemia, colon cancer, thymic epithelial cell cancer, renal cell carcinoma, transitional cell carcinoma of the renal-pelvis, and glioblastoma multiforme, suggests that the PIBF protein may be important for a large variety of cancers to escape immune surveillance. Pancreatic cancer can be added to this list of advanced cancers that respond to mifepristone therapy. The fact that it seems to work even when standard chemotherapy, immunotherapy, and targeted therapies have failed to work on patients with widespread cancer, including a large variety of cancers, could suggest that the PIBF protein may be a mechanism used by stem cells to escape immune surveillance. Since there are no other treatment options, we have elected not to repeat computerized tomography scans to evaluate whether the lesions have regressed but we believe clinically they must have. Citation Format: Jerome H. Check, Diane Check, Carrie Wilson, Maya Srivastava, Trina Poretta, James Aikins. Treatment with oral mifepristone enables a patient with end-stage pancreatic cancer in hospice, on a morphine drip, to restore a decent quality of life [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 695.