The chance that an old antidepressant could represent a novel treatment in the fight against prostate cancer is becoming reality. In an article in Prostate Cancer and Prostatic Diseases, researchers explore the impact of monoamine oxidase (MAO) on cancer growth and to what degree inhibiting MAO can influence outcomes, including metastasis in patients with certain forms of prostate cancer.

Senior author, Jean Shih, PhD, a professor at the University of Southern California (USC) School of Pharmacy, first author Mitchell Gross, MD, PhD, research director at the Lawrence J. Ellison Institute for Transformative Medicine of USC, and her team set out to explore the effects of phenelzine, a monoamine oxidase (MAO) inhibitor, on prostate cancer and associated metastasis and disease in patients with recurrent, castrate-sensitive prostate cancer. 

MAO inhibitors are effective antidepressants due to their beneficial pharmacotherapeutic effects of restoring neurotransmitter balance; however, the USC researchers write that these agents can also alter androgen receptor signaling, which they describe as the primary influence in the growth of prostate cancer. Using an open-label, single arm clinical trial, the team examined 20 subjects who met eligibility criteria, which included having a diagnosis of  biochemical-recurrent prostate cancer defined by PSA of 0.4 ng/ml or greater (after surgical prostatectomy) or a PSA of 2 ng/mL or higher above nadir (after radiation therapy). The subjects also had to show no evidence of metastatic growth on imaging tests and normal androgen levels.  

The patients received phenelzine 30 mg orally twice daily. In addition to the primary outcome, which was decline in PSA, the team also assessed mood symptoms using the hospital anxiety depression score (HADS) questionnaire. The team reported that at 12 weeks, 17 of the 20 subjects continued treatment, and the researchers observed PSA declines of 30% and greater in four subjects (24%) and of 50% and greater in one subject (6%). Although side effects such as dizziness, hypertension and edema were reported, only three events required treatment discontinuation and included two episodes of grade 3 syncope (cycle 12 and cycle 14) and one episode of grade 4 hypertension (cycle 4). The evaluation of the HADS questionnaires demonstrated no change in depressive symptoms with treatment; however, a significant decrease in anxiety observed was observed.

The team highlighted the value of their findings by first reiterating the medical necessity of this intervention, citing that prostate cancer was second only to skin cancer in men in the United States. Because prostate cancer is treated primarily through surgery, with or without concurrent radiation therapy, resurgence of cancer after these interventions leaves only the limited additional option of hormonal therapy, which can result in significant collateral consequences, including diminished quality of life.

“To our knowledge, this study is the first clinical trial of a MAO inhibitor in cancer patients,” says Dr. Shih. “If our findings are confirmed, this could part of a new avenue for patients that could avoid undesirable side effects of standard therapies,” says Dr. Gross.

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