Lippman S M, Benner S E, Hong W K
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1994 Apr 1;54(7 Suppl):2025s-2028s.
Chemoprevention is a clinical strategy to block or reverse carcinogenesis before the development of invasive cancer. Studies of chemoprevention in the lungs and upper aerodigestive tract have relied on the field carcinogenesis hypothesis, which predicts that diffuse epithelial injury will result from exposure of that epithelium to carcinogens. This hypothesis is supported by the frequent occurrence of multiple primary tumors within the exposed field. In addition, the understanding of carcinogenesis as a multistep process supports the use of interventions in damaged epithelium before the development of clinically invasive cancer. Current efforts are focused on applying to chemoprevention studies the increasing knowledge of the molecular events in carcinogenesis. In our program, clinical trials in lung and head and neck chemoprevention have focused on individuals with evidence of field carcinogenesis, i.e., a history of previous epithelial cancer or the presence of premalignant lesions. These trials include studies to develop clinically applicable intermediate markers of carcinogenesis and large Phase III trials to evaluate the efficacy of the retinoid isotretinoin in preventing second primary tumors following head and neck or lung cancers.
化学预防是一种在浸润性癌症发生之前阻断或逆转致癌过程的临床策略。肺部和上呼吸道消化道的化学预防研究依赖于场致癌假说，该假说预测上皮细胞暴露于致癌物会导致弥漫性上皮损伤。暴露区域内频繁出现多个原发性肿瘤支持了这一假说。此外，将致癌作用理解为一个多步骤过程，也支持在临床浸润性癌症发生之前对受损上皮进行干预。目前的努力集中在将越来越多关于致癌分子事件的知识应用于化学预防研究。在我们的项目中，肺癌和头颈癌化学预防的临床试验主要针对有场致癌证据的个体，即有既往上皮癌病史或存在癌前病变的个体。这些试验包括开发临床上适用的致癌中间标志物的研究，以及评估维甲酸异维甲酸预防头颈癌或肺癌后第二原发性肿瘤疗效的大型III期试验。
