Not Significant But Important

Abstract

Armstrong and colleagues report the result of a large Phase IIb randomized trial evaluating the effectiveness of a preparation of the Bowman Birk Inhibitor compared with an oral placebo in reversing the extent of oral leukoplakia as measured visually by pathology or a battery of intermediate end points. In this editorial, we review the report of this negative clinical trials result to highlight the clinical trial process used in evaluating this previously promising chemoprevention agent. Publishing this report is important to address concerns with publication bias. The challenges in running a chemoprevention trial are reviewed with suggestions to enhance progress going forward. Conceptually, developing drugs to intercept the early stages of carcinogenesis is very attractive, but progress in this area has been slow. Two opportunities to overcome this reality are discussed. These measures include the broader use of neoadjuvant, window-ofopportunity trials with new candidate chemoprevention agents to get more textured information about the mechanistic impact of the drug exposure in previously untreated early tumor tissue. In addition, we discuss the use of new intermediate end point markers such as with optical imaging tools to obtain a more objective and quantitative assessment of drug response. Cancer Prev Res; 6(5);

Advances in the Chemopreventive Targeting of Oral Carcinogenesis

“…Following on these promising findings, identifying common genomic and molecular signaling nodes and biomarkers of neoplastic transformation in oral premalignant lesions should also ultimately aid in the stratification and selection of at-risk patients. Moreover, this will eventually contribute to the development and clinical application of more predictable chemopreventive drugs [8,14,94]. However, this task offers many challenges, especially in a malignant disease where traditional risk factors such as tobacco use and betel quid chewing are still largely responsible for its occurrence.…”

Letter from the Editor

“…11, 12) and examined the ongoing challenges and opportunities of cancer prevention trials by publishing several perspectives and commentaries on this topic by some of the most established investigators in the field (e.g., Brenner, Hawk, Mulshine, Ondrey, Stoffel, Perloff and Steele; refs. [13][14][15][16].…”