Parnes Howard L, House Margaret G, Kagan Jacob, Kausal David J, Lieberman Ronald
Prostate and Urologic Cancer Researh Group, Division of Cancer Prevention, National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA.
J Urol. 2004 Feb;171(2 Pt 2):S68-74; discussion S75. doi: 10.1097/01.ju.0000107220.64675.74.
We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used.
The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models.
Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention.
Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.
我们描述了当前美国国立癌症研究所化学预防剂的开发计划，并总结了所使用的中间终点。
美国国立癌症研究所目前正在多种信息丰富的队列中开展一系列关于有前景的化学预防剂的研究，例如高级别前列腺上皮内瘤变、癌症家族史阳性、前列腺特异性抗原升高但活检阴性、等待观察的前列腺癌、等待确定性治疗的前列腺癌以及普通人群。每种正在研究的药剂的理论依据都来自流行病学观察、前列腺癌治疗试验、大型癌症预防研究的二次分析、对癌症生物学和前列腺癌发生的理解，以及/或者实验动物模型。
癌症发生是一个数十年的多步骤过程，其特征是控制细胞增殖、程序性细胞死亡和分化的正常调节途径受到破坏。给予药物以逆转、抑制或减缓这种恶性转化过程被称为化学预防。
化学预防是降低前列腺癌发病率和死亡率的一种有前景的方法。目前有多种药剂正在进行2期临床试验研究，其中一些可能值得随后在以明确癌症终点的3期试验中进行评估。美国国立癌症研究所也正在赞助两项正在进行的大型3期试验，即前列腺癌预防试验和硒与维生素E癌症预防试验。
