From the Journals

Antidepressant could treat recurrent prostate cancer



The monoamine oxidase inhibitor phenelzine (Nardil) appeared safe and active in a phase 2 trial of patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer.

“We sought to investigate if phenelzine would exert an anticancer effect demonstrated by decreasing PSA [prostate-specific antigen] values in biochemically recurrent prostate cancer patients,” study author Mitchell E. Gross, MD, PhD, of the University of Southern California, Los Angeles, and colleagues wrote. Their findings were published in Prostate Cancer and Prostatic Diseases.

The single-arm study included 20 patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer who received primary treatment with either radical prostatectomy (n = 18) or radiotherapy (n = 2). Study subjects had normal levels of free testosterone (50 ng/dL or above) and showed no evidence of metastatic disease on bone and CT imaging.

With respect to dosing, 18 patients were successfully titrated to the target dose of 30 mg of oral phenelzine twice daily. Five of these patients subsequently had their dose increased to 45 mg twice daily. Each dosing cycle was 28 days, with escalations occurring during the first 2 weeks of therapy.

Therapy was continued until disease progression, patient preference, therapy interruption of more than 2 weeks from study-related toxicity, or physician decision.

The primary outcome measured was PSA reduction of at least 50% from baseline. Psychiatric outcomes were also evaluated using the Hospital Anxiety and Depression Scale.

The median treatment duration was 326 days (range, 40-954 days). Among 20 evaluable patients, 5 patients (25%) achieved a PSA reduction of at least 30% from baseline, and 2 patients (10%) achieved a reduction of at least 50% from baseline.

At 12 weeks, 17 patients were still on treatment. Four patients (24%) had PSA reductions of at least 30%, and one patient (6%) had a PSA reduction of at least 50%.

The most common grade 2 or higher phenelzine-related adverse effects were dizziness (35%), hypertension (30%), and edema (10%). Serious toxicities included one case of grade 4 hypertension and two cases of grade 3 syncope, which required treatment discontinuation.

With respect to mood outcomes, Hospital Anxiety and Depression Scale scores showed a significant decline in anxiety symptoms but no difference in depressive symptoms.

The researchers acknowledged that two key limitations of this study were the small sample size and the absence of a placebo arm. Hence, the results may not accurately reflect long-term clinically relevant outcomes, such as overall survival or disease progression.

“Further studies would be needed to determine if [monoamine oxidase inhibitors], used alone or in combination with other agents, may delay clinical progression and metastasis,” the researchers concluded.

This study was funded by the USC-Taiwan Center for Translational Research and the National Cancer Institute. Some of the authors disclosed financial affiliations with Amgen, Astellas, AstraZeneca, Bayer, and other companies.

SOURCE: Gross ME et al. Prostate Cancer Prostatic Dis. 2020 Mar 3. doi: 10.1038/s41391-020-0211-9.

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