Abstract 4680: Biomarkers of adherence and efficacy: modulation of biomarkers of DNA damage in a Phase 1b trial of post-surgical oral cancer patients on a long-term food-based prevention study with black raspberries.
Authors: Uhrig Lana K. , Knobloch Thomas J. , Casto Bruce C. , Agrawal Amit , Schuller David E. , Teknos Theodoros N. , Ozer Enver , Old Matthew O. , Sardo Christine L. , Xueliang Jeff , Clinton Steven K. , Pearl Dennis K. , Weghorst Christopher M. 
Published: August 2014

Abstract
Background: Consumption of phytochemical-rich fruits and vegetables is associated with a lower risk of oral cancer and protection against oxidative stress-mediated damage from reactive oxygen species (ROS). We proposed that antioxidant components in black raspberries (BRBs) could “scavenge” ROS and diminish oxidative stress burden. We tested the hypothesis that a long-term, low-dose administration of BRBs to a population of disease-free oral cancer survivors is both (i) achievable and (ii) will result in the attenuation of oxidative DNA damage.
Methods: Participants were assigned to consume 0, 4, or 8 gms of BRBs daily for 6 months and provided self-report logbooks of adherence. Mass spectrometry (MS) of urine for dimethyl ellagic acid (DMEA) at baseline, 10, and 20 wks was utilized as a biomarker of adherence. ELISA of urine was used to measure 8-hydroxy-2’-deoxyguanosine (8-OHdG). A logistic regression model was used to determine factors associated with willingness to continue on the regimen once enrolled.
Results: 112 participants were enrolled and assigned to a BRB regimen. 81 participants (72%) provided self-reported adherence logbooks. Adherence at wks 2, 10 and 20 was 92% (n=77), 85% (n=55), and 86% (n=44) respectively. The regimen was well tolerated with no significant adverse events. MS/MS measurements of DMEA was 10 fold higher (p&lt;0.0001; CI: 4-25) at 10 and 20 wks in participants treated with BRBs vs control. ELISA measurements of 8-OHdG in urine at 10 wks was 1.28 fold lower (p&lt;0.0183; CI: 1.04-1.58) in patients treated with BRBs vs control. Logistic regression analysis revealed that those having the least travel distance (OR: 0.98 [10 and 20 wks] p&lt;0.03) and those having government insurance (OR: 3.96 [10 wks]; 7.04 [20 wks]; p&lt;0.02) or private insurance (OR: 5.1 [20 wks]; p&lt;0.01) vs those with no insurance were more likely to complete the study. Also, the analysis showed that past (OR: 3.85; p&lt;0.02) and current (OR: 3.82; p&lt;0.03) tobacco users were more likely reach 20 wks than never smokers. Furthermore, those having had no adjuvant therapy (OR: 4.5; p&lt;0.004) vs those having had chemotherapy and/or radiation were more likely to complete 20 wks of intervention.
Conclusions: A food-based prevention strategy utilizing BRBs in oral cancer survivors is safe and feasible. Compliance for those staying on regimen was high and factors identified that influenced continued participation included: having insurance, travel distance, having had adjuvant therapy, and tobacco use. While the number of active participants declined, those completing the intervention maintained outstanding levels of adherence (&gt;85%). Biomarkers of adherence were identified as an objective means of validating self-reported adherence. Moreover, 8-OHdG levels were reduced, providing a potentially useful biomarker of BRB efficacy.
Citation Format: Lana K. Uhrig, Thomas J. Knobloch, Bruce C. Casto, Amit Agrawal, David E. Schuller, Theodoros N. Teknos, Enver Ozer, Matthew O. Old, Christine L. Sardo, Jeff Xueliang, Steven K. Clinton, Dennis K. Pearl, Christopher M. Weghorst. Biomarkers of adherence and efficacy: modulation of biomarkers of DNA damage in a Phase 1b trial of post-surgical oral cancer patients on a long-term food-based prevention study with black raspberries. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4680. doi:10.1158/1538-7445.AM2013-4680