Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary.
Cancer Prev Res (Phila). 2021 May;14(5):573-580. doi: 10.1158/1940-6207.CAPR-20-0598. Epub 2021 Mar 1.
Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects ( = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; = 0.28); total ACF burden was also similar (-2.3% difference of means; = 0.83). Adenoma recurrence rates at 6 months were similar by arm ( > 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied. PREVENTION RELEVANCE: We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.
多酚 E（Poly E）是一种绿茶多酚制剂，其最活跃的成分是表没食子儿茶素没食子酸酯（EGCG）。我们研究了多酚 E 在直肠异形隐窝病灶（ACF）患者中的癌症预防功效和安全性，这些病灶代表结直肠癌的潜在前体。合格的受试者既往有结直肠高级腺瘤或癌症，且在预注册的 chromoendoscopy 中存在≥5 个直肠 ACF。受试者（=39 人）被随机分为 6 个月的口服多酚 E（780mg EGCG）每日或安慰剂。治疗组的基线特征相似（所有 P >0.41）；39 名受试者中的 32 名（82%）完成了 6 个月的治疗。主要终点是 chromoendoscopy 前后直肠 ACF 减少的百分比。在 32 名受试者（15 名 Poly E，17 名安慰剂）中，直肠 ACF 数量的变化百分比（基线与 6 个月）在研究组之间无显著差异（均值差异 3.7%；=0.28）；总 ACF 负担也相似（均值差异-2.3%；=0.83）。6 个月时腺瘤复发率在各组之间相似（>0.35）。各组的总药物摄入无显著差异；31 名（79%）受试者接受了≥70%的规定剂量的 Poly E。Poly E 耐受性良好，不良反应（AE）在各组之间无显著差异。安慰剂组中有 1 名受试者发生 2 例 3 级 AE；1 例受试者出现归因于治疗的 2 级肝转氨酶升高。总之，与安慰剂相比，6 个月的 Poly E 治疗并未显著减少直肠 ACF 的数量。在研究剂量下，Poly E 耐受性良好，无明显毒性。预防相关性：我们报告了一项在结直肠癌高危人群中进行的多酚 E 化学预防试验。结果表明，多酚 E 耐受性良好，但不能显著减少直肠异形隐窝病灶的数量，这是结直肠癌的替代终点生物标志物。
