EFFECTS OF FRUIT & VEGETABLE EXTRACTS ON CANCER MARKERS

描述(申请人提供)：头颈部鳞状细胞癌(HNSCC)是一种侵袭性的上皮性肿瘤，约占美国新诊断的非皮肤恶性肿瘤的5%。在原发癌已被成功治疗的同时，二次原发肿瘤的发展是决定早期头颈癌患者生存的最重要因素。为了提高头颈部癌症患者的生存率，有效的继发性恶性肿瘤的化学预防方案是必不可少的。这项前瞻性、随机、双盲的II期化学预防试验旨在评估水果和蔬菜提取物(F&V)对细胞周期调节、DNA损伤/修复和免疫功能的影响，这些作用与既往HNSCC患者SPTS的发生有关。我们相信，补充F&V提取物可能会提供没有副作用的疗效，这一组合对于高危癌症患者和低风险健康人群的长期化学预防至关重要。这些生物标志物的应用将大大缩短有前景的化学预防药物的临床疗效评估所需的时间。在12周的试验期结束时，我们将获得至少120名受试者(每组60人)的生物标记物数据。主要目的是验证F&V提取物可以调节主要中间终点的工作假设，即细胞周期调节蛋白p27的表达，该蛋白与HNSCC患者的肿瘤进展、复发和无病生存有关。次要终点是细胞增殖(Ki-67)、DNA损伤/修复(彗星试验)和免疫功能(T细胞激活)。这项拟议的研究将使用一种新的补充和替代(CAM)方法来进行癌症化学预防。这一结果将为以下方面提供关键信息：(1)替代终点(S)在监测F&V提取物的生物学效应中的使用；(2)F&V提取物预防HNSCC的机制；(3)F&V提取物在HNSCC患者中使用补充的可行性。这项第二阶段试验的有希望的研究结果将为更大的第三阶段化学预防试验奠定基础，以评估F&V提取物在预防HNSCC患者SPTS方面的应用。

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial neoplasm that represents approximately 5% of newly diagnosed noncutaneous malignancies in the United States. While the primary cancers have been successfully treated, the development of second primary tumors (SPTs) is the most important factor determining the survival in early-stage head and neck cancer patients. To improve the survival of head and neck cancer patients, an effective program of chemoprevention for second malignancies is essential. This prospective, randomized double-blind Phase II chemoprevention trial is designed to assess the effects of fruit and vegetable (F&V) extracts on cell cycle regulation, DNA damage/repair, and immune function, which are associated with the development of SPTs in patient with previous HNSCC. We believe that supplementation of F&V extracts may provide efficacy without side effects, a combination that is critical for long-term chemoprevention in both high-risk cancer patients and low-risk healthy populations. The application of such biomarkers will significantly shorten the time required for clinical efficacy evaluation for promising chemopreventive agents. We will have biomarker data on at least 120 subjects (60 each arm) at the end of the 12 week trial period. The primary aim is to test the working hypothesis that F&V extracts can modulate primary intermediate endpoint, the expression of a cell cycle regulatory protein, p27, which is associated with tumor progression, recurrence, and disease-free survival of patients with HNSCC. The secondary endpoints are cell proliferation (Ki-67), DNA damage/repair (Comet assay), and immune function (T-cell activation). The proposed research will use a novel complementary and alternative (CAM) approach to cancer chemoprevention. The results will provide critical information on: (1) the use of surrogate endpoint(s) in monitoring the biological effects of F&V extracts, (2) the mechanisms of F&V in preventing HNSCC, and (3) the feasibility of using supplementation of F&V extract in HNSCC patients. Promising study results from this Phase II trial will lay the groundwork for larger Phase III chemoprevention trial to assess the application of F&V extracts in preventing SPTs for patients with HNSCC.