PURPOSE Monoamine oxidase A (MAOA) influences prostate cancer growth and metastasis in pre-clinical models. We examined effects of phenelzine (a monoamine oxidase inhibitor) in patients with biochemical recurrent castrate-sensitive prostate cancer. MATERIALS AND METHODS An open-label single arm clinical trial enrolled subjects with biochemical recurrent prostate cancer defined by PSA ≥ 0.4 ng/ml (post prostatectomy) or PSA ≥ 2 ng/ml above nadir (post-radiation therapy); no evidence of metastasis on imaging; and normal androgen levels. Subjects received phenelzine 30 mg orally twice daily. Mood symptoms were assessed with the hospital anxiety depression score (HADS) questionnaire. The primary endpoint was the proportion of patients who achieved a PSA decline of ≥50% from baseline. RESULTS Characteristics of the 20 eligible patients enrolled included: mean ± SD age 66.9 ± 4.8 years and PSA 4.7 ± 5.8 ng/dl. Maximal PSA declines ≥30% and ≥50% were observed in 25% (n = 5/20) and 10% (n = 2/20) of subjects, respectively. At 12 weeks, 17 subjects remained on treatment with PSA declines ≥30% and ≥50% of 24% (n = 4/17) and 6% (n = 1/17), respectively. Common toxicities observed included dizziness (grade 1 = 45%, grade 2 = 35%), hypertension (grade ≥ 2 = 30%), and edema (grade 1 = 25%, grade 2 = 10%). There was one episode of grade 4 hypertension (cycle 4) and two episodes of grade 3 syncope (cycle 12 and cycle 14) requiring treatment discontinuation. HADS questionnaires demonstrated a significant decrease in anxiety with no change in depressive symptoms on treatment. CONCLUSIONS Phenelzine demonstrated efficacy in patients with biochemical recurrent castrate-sensitive prostate cancer. Most treatment-related toxicities were mild, but rare significant and reversible cardiovascular toxicities were observed. Therapies directed at MAOA may represent a new avenue for treatment in patients with recurrent prostate cancer.

中文翻译：

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单胺氧化酶抑制剂苯乙肼在生化复发性前列腺癌中的二期试验。

目的单胺氧化酶 A (MAOA) 在临床前模型中影响前列腺癌的生长和转移。我们检查了苯乙肼（一种单胺氧化酶抑制剂）对生化复发性去势敏感前列腺癌患者的影响。材料和方法 一项开放标签单臂临床试验纳入了生化复发性前列腺癌受试者，其定义为 PSA ≥ 0.4 ng/ml（前列腺切除术后）或 PSA ≥ 2 ng/ml 高于最低点（放射治疗后）；影像学上无转移证据；和正常的雄激素水平。受试者每天两次口服苯乙肼 30 mg。使用医院焦虑抑郁评分（HADS）问卷评估情绪症状。主要终点是 PSA 比基线下降≥50% 的患者比例。结果 入选的 20 名合格患者的特征包括：平均 ± SD 年龄 66.9 ± 4.8 岁和 PSA 4.7 ± 5.8 ng/dl。分别在 25% (n = 5/20) 和 10% (n = 2/20) 的受试者中观察到最大 PSA 下降≥30% 和≥50%。在第 12 周时，17 名受试者继续接受治疗，PSA 下降分别为 24% (n = 4/17) 和 6% (n = 1/17) ≥ 30% 和 ≥ 50%。观察到的常见毒性包括头晕（1 级 = 45%，2 级 = 35%）、高血压（≥ 2 = 30%）和水肿（1 级 = 25%，2 级 = 10%）。有 1 次 4 级高血压发作（第 4 周期）和 2 次 3 级晕厥发作（第 12 和第 14 周期）需要停止治疗。HADS 问卷显示焦虑显着减少，治疗后抑郁症状没有变化。结论苯乙肼在生化复发性去势敏感前列腺癌患者中显示出疗效。大多数与治疗相关的毒性是轻微的，但很少观察到显着且可逆的心血管毒性。针对 MAOA 的治疗可能代表了治疗复发性前列腺癌患者的新途径。