Abstract 4876: Long-term high quality survival with single agent mifepristone treatment despite advanced lung cancer and advanced renal cell carcinoma - 2 case reports
Authors: Check Jerome H. , Check Diane , Aly Jasmine , Wilson Carrie 
Published: July 2016

The objective is to report long-term high quality survival in 2 patients with advanced cancer treated by single agent mifepristone.

Case 1: An 80 year old woman was admitted to the ICU for respiratory failure. Chest x-ray revealed many lung lesions most consistent with lung cancer with multiple lung metastases. She was subsequently admitted several more times with very low arterial pO2 levels and her serum sodium progressively decreased to 118 mmol/L. The radiologic and clinical diagnosis was probable advanced lung cancer with the syndrome of inappropriate antidiuretic hormone (SIADH) from ectopic tumor production of arginine vasopressin. She refused surgery or chemotherapy. She agreed to experimental use of 200mg daily oral mifepristone. Her pO2 returned to 99-100 mmHg with 1 month and her sodium returned to normal. Six weeks later all her lung lesions were gone by CT scan. Three and a half years after initial treatment, her PO2 remains 96-98 mmHg, she is feeling fine, and her CT-scan continues to show no tumors. Her treatment had been approved by the FDA on a compassionate basis.

Case 2 - A 60 year old male with was found to have bilateral renal cell carcinoma with metastases to local lymph nodes. He refused bilateral nephrectomy but agreed to only laparoscopic right hemi nephrectomy to remove the largest lesion, leaving the left kidney intact. He received FDA approval to use 200mg daily mifepristone because at that time there was no chemotherapy that was known to be effective. The left kidney lesions did not recede but stayed stable for 10 years. Furthermore, no new lesions appeared on bi-annual CT scan. After 10 years of therapy, he developed renal failure secondary to diabetes. At this time he underwent bilateral nephrectomy, followed by kidney transplant. 11 years from diagnosis he is doing well. Neither patient has reported any side effects to 200mg mifepristone daily despite a combined 14 years of treatment. The mechanism of action responsible for these phenomena has not been proven thus far. The proposed mechanism is that progesterone inhibits an intracytoplasmic immunomodulatory protein known as the progesterone induced blocking factor (PIBF). By inhibiting PIBF, the cellular immune cells (specifically natural killer (NK) cells) are able to attack the rapidly growing tumor cells. The FDA has approved an investigator initiated study for the use of single agent mifepristone for stage IV human non-small cell lung cancer which has progressed despite either 2 rounds of chemotherapy or 1 round of chemotherapy plus one round of biologic therapy. Mifepristone, a progesterone receptor modulator, has been demonstrated to inhibit the production of a 34-36 kDa intracytoplasmic splice variant of the 90 kDa centrosomally associated parent compound. However, this potent abortifacient failed to suppress serum PIBF levels.

Citation Format: Jerome H. Check, Diane Check, Jasmine Aly, Carrie Wilson. Long-term high quality survival with single agent mifepristone treatment despite advanced lung cancer and advanced renal cell carcinoma - 2 case reports. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4876.