A medication that is commonly prescribed to treat depression appeared well tolerated in patients with biochemical recurrent prostate cancer.
The use of Nardil (phenelzine), a medication commonly prescribed to treat depression, appeared safe and well tolerated in patients with biochemical recurrent (BCR) prostate cancer, according to results of a phase 2 clinical trial.
In most men, prostate cancer is adequately treated with a multitude of options that include radical prostatectomy, radiation or active surveillance. However, there is a certain percentage of people who will see the cancer return following initial treatment.
One therapy that has shown the ability to lower prostate-specific antigen (PSA) levels and has been used in those with recurrent prostate cancer is androgen deprivation therapy. However, it is associated with risks for side effects including osteoporosis, weight gain, decreased libido and the potential exacerbation of cardiac disease which has led some to question its use for early BCR prostate cancer, the researchers wrote.
To assess if Nardil, a type of monoamine oxidase (MAO) inhibitor that changes the way messages are sent from one nerve to another in the brain, would have an anti-cancer effect demonstrated by decreasing PSA levels in patients with BCR prostate cancer, the researchers conducted a study of 20 men between November 2014 and July 2017. The primary endpoint was the detection of a PSA decline of 50% or more from baseline, or the start of the study.
“To our knowledge, this study is the first clinical trial of (a) MAO inhibitor in cancer patients,” senior author Dr. Jean Shih, the Boyd P. and Elsie D. Welin Professor in Pharmacology and Pharmaceutical Sciences at USC School of Pharmacy, said in a press release.
Patients received Nardil orally on the first day of treatment and went through multiple cycles over a 28-day period. Dose escalation was used during the first two weeks of treatment to reach a target dose of 60 milligrams (mg) total for the day. After safety and tolerability were witnessed in the first 10 patients, the researchers changed the protocol to include an additional dose level of 45 mg twice daily for those treated at target dose for three cycles or more without any signs of grade 2 or higher side effects based on previous Food and Drug Administration approval for the treatment of depression.
The researchers were able to assess a PSA response in all the patients. A PSA decline of 50% or more was achieved in two patients. Five patients experienced a PSA decline of at least 30%. Overall, PSA declines were observed in 11 patients during Nardil treatment with a maximum PSA decline of 74%.
Approximately 80% of the participants reported experiencing dizziness as a side effect. There was one instance of hypertension and two instances of loss of consciousness that led to study withdrawal for those participants.
The study, according to its authors, had some limitations, including no placebo control group and a small sample size. The researchers also noted that it is possible that the effect observed on the PSA levels may not translate to improvements in clinically significant endpoints in overall survival, but that more research is needed.
“If our findings are confirmed, this could be part of a new avenue for patients that could avoid undesirable side effects of standard therapies,” first author Dr. Mitchell Gross, a medical oncologist and research director at the Lawrence J. Ellison Institute for Transformative Medicine of USC, said in the release.