Kumar Nagi B, Pow-Sang Julio, Spiess Philippe, Dickinson Shohreh, Schell Michael J
Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA.
Department of Urology, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA.
Oncotarget. 2020 Apr 7;11(14):1218-1234. doi: 10.18632/oncotarget.27529.
Prostate cancer (PCa) is the most common cancer in American men. Additionally, African American Men (AAM) are 60% more likely to be diagnosed with PCa and 2.4 times more likely to die from this disease compared to Caucasian men (CM). To date, there are few strategies effective for chemoprevention for men with localized PCa. There is thus a need to continue to evaluate agents and strategies for chemoprevention of prostate cancer. Epidemiological, laboratory and early phase clinical trials have shown that the isoflavones modulates several biomarkers implicated in prostate carcinogenesis. The goal of this phase II randomized clinical trial was to explore the comparative effectiveness and safety of 40 mgs of aglycone isoflavones in AAM and CM with localized PCa in the pre-surgical period prior to radical prostatectomy. Thirty six participants (25 CM, 6AAM) were randomized to the isoflavone arm and 34 (25 CM, 7AAM) to the placebo arm, with 62 completing the intervention. Results indicated that isoflavones at a dose of 20 mgs BID for 3-6 weeks was well tolerated but did not reduce tissue markers of proliferation. A significant reduction in serum PSA was observed with isoflavone supplementation in CM compared to the placebo arm, but not observed in AAM. We observed no changes in serum steroid hormones with isoflavone supplementation. In AAM, a reduction in serum IGF-1 concentrations and IGF1: IGFBP-3 ratios were observed with isoflavone supplementation. Well-powered studies for longer duration of intervention may inform future trials with isoflavones, for chemoprevention of PCa.
前列腺癌(PCa)是美国男性中最常见的癌症。此外,与白人男性(CM)相比,非裔美国男性(AAM)被诊断出患有PCa的可能性要高60%,死于这种疾病的可能性是白人男性的2.4倍。迄今为止,对于局限性PCa男性,几乎没有有效的化学预防策略。因此,有必要继续评估前列腺癌化学预防的药物和策略。流行病学、实验室和早期临床试验表明,异黄酮可调节前列腺癌发生过程中涉及的几种生物标志物。这项II期随机临床试验的目的是探讨在根治性前列腺切除术术前,40毫克苷元异黄酮对AAM和CM局限性PCa患者的相对有效性和安全性。36名参与者(25名CM,6名AAM)被随机分配到异黄酮组,34名(25名CM,7名AAM)被分配到安慰剂组,62人完成了干预。结果表明,每天两次服用20毫克异黄酮,持续3 - 6周,耐受性良好,但并未降低增殖组织标志物。与安慰剂组相比,CM补充异黄酮后血清PSA显著降低,但AAM未观察到这种情况。补充异黄酮后,我们未观察到血清甾体激素有变化。在AAM中,补充异黄酮后观察到血清IGF - 1浓度和IGF1:IGFBP - 3比值降低。针对更长干预时间的有力研究可能为未来异黄酮预防PCa的试验提供参考。