Microgranular Curcumin Biomarker Trial in Head and Neck Squamous Cell Carcinoma

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* DESCRIPTION (provided by applicant): Up to 50% of head and neck cancer (HNSCC) patients with advanced stage disease develop recurrences and early stage disease patients develop second primaries. Therefore preventing any of the steps of neoplastic transformation is a promising strategy. The mission of this RFA is to explore the mechanisms involved in nutritional agents in cancer, and the overall goal of this study is to determine whether curcumin can be used as a nutritional intervention agent in precancerous lesions of the upper aerodigestive tract to prevent cancer recurrence and ultimately reduce future health care costs. However the first step is to validate clinically useful biomarkers as indicators of curcumin response, which is best achieved in HNSCC patients where the biomarkers being tested is activated in 100% of tumors. There is a worldwide need for intervention studies using intermediate and surrogate biomarkers as endpoints to identify potential agents for chemoprevention of recurrence. Intermediate endpoints are necessary to more rapidly assess interventions for primary cancer prevention and address the feasibility posed by large patient numbers, length of study, and cost when cancer occurrence or recurrence is used as an endpoint. This clinical trial with curcumin could validate important biomarkers for studies with curcumin and correlate the biological effect of modulating these biomarkers, thus decreasing the number of subjects required in future interventional studies. In this proposal we will determine if the Akt/mTOR pathway components, overexpressed in ~90% of HNSCC, are potential biomarkers for future chemoprevention/adjuvant studies with curcumin, and decipher the mechanism of the nutritional interventional agent curcumin on cancer biology and prevention. To achieve this goal, 15 newly diagnosed head and neck cancer patients will receive a microgranular formulation of curcumin that allows for prolonged contact that has achieved double the plasma concentrations in two pilot patients compared to the standard capsule formulation used in a phase 2 pancreatic cancer trial, and has also achieved biological response for 3-4 weeks prior to standard treatment in these same two patients. Levels of curcumin will be determined in the plasma and tumor using HPLC, and repeat biopsies taken before and after curcumin treatment will be used to evaluate biomarker response to curcumin. The change in biomarkers in tumors from initial biopsy to final biopsy will be compared to a control group of patients with biopsies taken at the same time interval from our existing tissue bank and will be used to identify and validate biomarkers affected by the nutritional intervention agent curcumin. Results from this study will be used for subsequent studies with preneoplastic lesions patients. PUBLIC HEALTH RELEVANCE: Overall survival rates for head and neck squamous cell cancers have not improved significantly in the last few decades, due to the development of recurrences and second primaries as a result of precancerous changes from tobacco. Curcumin, a novel safe nutritional interventional agent has exciting potential usage as a preventive/adjuvant agent, and prevents tumor formation by inhibiting an important molecular pathway AKT/MTOR that is shown to cause cancer progression, which we will test as a tumor marker in this clinical trial with curcumin. We will also determine curcumin's effects on gene products regulated by AKT/MTOR shown to be important in the step-wise progression to invasive cancer.