Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial neoplasm that represents approximately 5% of newly diagnosed noncutaneous malignancies in the United States. While the primary cancers have been successfully treated, the development of second primary tumors (SPTs) is the most important factor determining the survival in early-stage head and neck cancer patients. To improve the survival of head and neck cancer patients, an effective program of chemoprevention for second malignancies is essential. This prospective, randomized double-blind Phase II chemoprevention trial is designed to assess the effects of fruit and vegetable (F&V) extracts on cell cycle regulation, DNA damage/repair, and immune function, which are associated with the development of SPTs in patient with previous HNSCC. We believe that supplementation of F&V extracts may provide efficacy without side effects, a combination that is critical for long-term chemoprevention in both high-risk cancer patients and low-risk healthy populations. The application of such biomarkers will significantly shorten the time required for clinical efficacy evaluation for promising chemopreventive agents. We will have biomarker data on at least 120 subjects (60 each arm) at the end of the 12 week trial period. The primary aim is to test the working hypothesis that F&V extracts can modulate primary intermediate endpoint, the expression of a cell cycle regulatory protein, p27, which is associated with tumor progression, recurrence, and disease-free survival of patients with HNSCC. The secondary endpoints are cell proliferation (Ki-67), DNA damage/repair (Comet assay), and immune function (T-cell activation). The proposed research will use a novel complementary and alternative (CAM) approach to cancer chemoprevention. The results will provide critical information on: (1) the use of surrogate endpoint(s) in monitoring the biological effects of F&V extracts, (2) the mechanisms of F&V in preventing HNSCC, and (3) the feasibility of using supplementation of F&V extract in HNSCC patients. Promising study results from this Phase II trial will lay the groundwork for larger Phase III chemoprevention trial to assess the application of F&V extracts in preventing SPTs for patients with HNSCC.
| Datta, Mridul; Shaw, Edward G; Lesser, Glenn J et al. (2018) A Randomized Double-Blind Placebo-Controlled Trial of Fruit and Vegetable Concentrates on Intermediate Biomarkers in Head and Neck Cancer. Integr Cancer Ther 17:115-123 |
