Clinical trials in chemoprevention of head and neck cancers

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies and has significant mortality. Its multi-step cumulative features strongly support early management. Cancer chemoprevention has been accepted as a promising intervention for early management, and has made enormous progresses over the past 30 years due to the large number of research studies including many randomized clinical trials. Overall, chemoprevention is an appealing approach for fighting HNSCC because it is generally safe, cost-effective, and widely available. In this review, we summarize and discuss new findings and evidences from the most recent clinical trials in chemoprevention of HNSCC. Our literature search is limited only to those trials published within the past 10 years (2001-2011). Based on our review, the most extensively studied agents/compounds for chemoprevention continue to be retinoids (e.g., 13-cRA). Additional agents considered include COX inhibitors, Vitamin A and E forms, and green tea and other natural extracts. However, we found disappointing results in the studies using retinoids, COX inhibitors and vitamin forms, while encouraging outcomes were found with most natural extracts. Further study is warranted for validation or improvement of treatment efficacy with current agents and strategies. Future research may include identification of new biomarkers/targets, improvement of bioavailability or tissue penetration, combinations of different compounds (or development of dual-action agents) to act on multiple pathways, and specific study of non-smoking related or other untraditional causes.