Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials

Andrew S Holpuch1, Kashappa-Goud H Desai2, Steven P Schwendeman2, Susan R Mallery3
1Division of Oral Maxillofacial Surgery, Pathology and Anesthesiology, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA
2Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA
3Division of Oral Maxillofacial Surgery, Pathology and Anesthesiology, College of Dentistry, The Ohio State University, Columbus, OH 43210; The Ohio State University Comprehensive Cancer Center, USA
DOI: 10.4103/1477-3163.85185

ABSTRACT

Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have assessed the therapeutic efficacy of diverse chemopreventive agents. The standard of care for more advanced oral dysplastic lesions entails surgical excision and close clinical follow-up due to the potential (~33%) for local recurrence at a similar or more advanced histological stage. The purpose of this review was to identify prominent oral cancer chemoprevention clinical trials, assess their overall therapeutic efficacy, and delineate effects of local versus systemic drug administration. In addition, these compiled clinical trial data present concepts for consideration in the design and conduction of future clinical trials.

Keywords: Chemoprevention, local drug delivery, oral cancer, pharmacologic advantage.