An antidepressant in use for decades, repurposed to fight prostate cancer, shows promise in helping patients whose disease has returned following surgery or radiation, a pilot study at USC shows.
Phenelzine, a MAO inhibitor, represents a potential new treatment direction with fewer side effects for men with recurrent prostate cancer, researchers said.
“To our knowledge, this study is the first clinical trial of an MAO inhibitor in cancer patients,” senior author Jean Shih, a University Professor in USC’s School of Pharmacy who has studied the enzyme MAO, or monoamine oxidase, for four decades, said in as statement. .
The research appears in Prostate Cancer and Prostatic Diseases.
“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 Mitchell Gross, a medical oncologist and research director at the Lawrence J. Ellison Institute for Transformative Medicine of USC, said in a statement. Gross and Shih have been collaborating for several years to bring her research out of the lab and into the clinic.
In the study, 11 of 20 participants had a measurable decline in their PSA levels after 12 weeks of twice-a-day treatment, with the greatest decline in PSA being a 74% drop.
In prostate cancer, MAO inhibitors disrupt androgen receptor signaling — the main growth pathway for prostate cancer. Previous studies with animals and human prostate cancer cell lines showed that MAO inhibitors decreased the growth and spread of prostate cancer, the researchers found.
Because the MAO inhibitor phenelzine is already FDA-approved, the researchers were able to rapidly design and implement a pilot study to test the drug’s ability to fight cancer.
For this study, researchers enrolled 20 participants who had been treated for prostate cancer and who had elevated PSA levels. Patients received the MAO inhibitor phenelzine twice a day for 12 weeks. Fifty-five percent of the men experienced PSA declines; five of them saw PSA level declines of 30% or more; two participants saw decreases of 50% or more.
Three patients had to drop out due to dizziness or hypertension.
The main limitations of the study include the lack of a placebo comparison group and the small sample size, researchers said. Additional studies are planned.
