Cancer Chemoprevention: Progress and Promise

Extract

In the relatively brief history of cancer chemoprevention, hundreds of chemoprevention studies have been reported. The vast majority were uncontrolled studies that were designed and reported in a nonrigorous fashion, which perhaps resulted largely from the zealousness of early chemoprevention researchers to nurture growth of an exciting novel approach through its infancy. Nevertheless, limitations characterizing many of these trials have tended to cloud chemoprevention's record of progress and promise. This tendency overlooks the solid cohort of definitive randomized trials that have successfully addressed many important clinical questions.

What distinguishes chemotherapy from chemoprevention? The simplest answer is that the former involves agents that treat cancer, and the latter involves agents that prevent cancer by either preventing or treating premalignant lesions. This distinction, however, is blurred by several recent results. Some agents, such as retinoids and tamoxifen, can both prevent and treat cancer. Several newer agents, including angiogenesis inhibitors and ras inhibitors, also show activity and promise in both preinvasive and invasive carcinogenesis. The distinction between premalignant and malignant lesions also is becoming blurred by new findings in molecular biology. For example, clonal expansion now is seen in preinvasive stages as well as in invasive stages of carcinogenesis. Furthermore, it is not always clear whether an agent is treating subclinical (e.g., microscopic) cancer or is treating premalignant lesions and thus preventing progression to cancer. Agents for which this issue has been raised are retinoids in the prevention of second primary head and neck cancers and tamoxifen in the prevention of breast cancer in the Breast Cancer Prevention Trial (BCPT).