Monoamine oxidase A-directed therapy for recurrent prostate cancer hits mark in early trial

Phenelzine, a monoamine oxidase inhibitor, shows therapeutic potential in patients with biochemical recurrent castrate-sensitive prostate cancer, according to the results of a phase II trial.

Twenty patients (mean age 66.9 years, PSA 4.7 ng/dl) with biochemical recurrent prostate cancer defined by prostate-specific antigen (PSA) ≥0.4 ng/ml (after prostatectomy) or PSA ≥2 ng/ml above nadir (after radiation therapy) received phenelzine 30 mg orally twice daily. All men had normal androgen levels, and there was no evidence of metastasis on imaging.

Results revealed maximal PSA declines of ≥30 percent in five patients (25 percent) and of ≥50 percent in two (10 percent). Out of the 17 patients who remained on treatment at 12 weeks, four (24 percent) and one (6 percent) achieved PSA declines of ≥30 percent and ≥50 percent, respectively.

Common toxicities recorded were dizziness (grade 1, 45 percent; grade 2, 35 percent), hypertension (grade ≥2, 30 percent), and oedema (grade 1, 25 percent; grade 2, 10 percent). One episode of grade 4 hypertension (cycle 4) and two episodes of grade 3 syncope (cycle 12 and cycle 14) resulted in treatment discontinuation.

In terms of mood symptoms, hospital anxiety depression score (HADS) questionnaire responses demonstrated a significant decrease in anxiety with no change in depressive symptoms on treatment.

Monoamine oxidase A (MAOA) has been shown to influence prostate cancer growth and metastasis in preclinical models. The present data indicate that therapies directed at MAOA may indeed represent a new avenue for treating recurrent prostate cancer.