Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Prostate Cancer Prostatic Dis. 2017 Sep;20(3):265-270. doi: 10.1038/pcan.2017.19. Epub 2017 Apr 25.
Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials.
Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC).
In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-hydroxy-2-deoxyguanosine, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multicomponent food supplement that included a 31.25% pomegranate extract found significant slowing of PSA increase in the food supplement arm vs placebo in men on active surveillance and those experiencing BCR.
Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo-controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multicomponent food supplement showed promising results in a phase II study in active surveillance and BCR patients.
临床前研究表明，石榴汁及其成分可抑制前列腺癌，随后开展了多项临床试验，以确定石榴产品是否能减缓前列腺癌的生长。本综述总结了临床前数据，并讨论了临床试验的结果。
试验对象包括正在接受主动监测的患者、新辅助治疗患者、接受局部治疗后发生生化复发（BCR）的患者以及转移性去势抵抗性前列腺癌（mCRPC）患者。
在 BCR 患者人群中，石榴汁和提取物的早期 II 期试验均显示 PSA 倍增时间（PSADT）显著延长，证实了石榴产品的安全性。尽管一项安慰剂对照 III 期试验表明，石榴提取物并未显著延长 BCR 患者的 PSADT，但对 MnSOD AA 基因型患者的预先计划的亚组分析显示，石榴提取物组的 PSADT 延长更为显著。在新辅助治疗人群中，一项大型试验显示，与安慰剂组相比，石榴组尿液中的乌索酸 A 显著增加，前列腺癌组织中氧化标志物 8-羟基-2-脱氧鸟苷（8-hydroxy-2-deoxyguanosine）减少，但无统计学意义。此外，一项包含多酚含量丰富的多种成分的复合食品补充剂的随机临床试验发现，与安慰剂组相比，在接受主动监测和发生 BCR 的男性中，该食品补充剂组的 PSA 增加速度显著减慢。
石榴汁和提取物安全，但在一项大型安慰剂对照试验中，并未显著改善 BCR 患者的结局。然而，MnSOD AA 基因型的 BCR 患者亚组似乎对石榴治疗的抗氧化作用有积极反应。新辅助治疗患者和 mCRPC 患者的 100%石榴产品 II 期试验结果为阴性。一项复合食品补充剂的 II 期研究在主动监测和 BCR 患者中显示出了有希望的结果。
