Phase II randomized placebo-controlled double-blind chemoprevention trial of fruit/vegetable concentrates on intermediate biomarkers in head/neck cancer.

Abstract

1521 Background: Head/neck cancer (HNC) patients (pts) are at high risk for developing second primary tumors (SPT). Juice-Plus+ is a proprietary whole food based nutritional supplement which includes juice powder concentrates from 17 different fruits, vegetables and grains (www.juiceplus.com). We conducted a chemoprevention trial to evaluate the effect of this intervention on surrogate endpoint biomarkers (SEB) associated with SPTs. Methods: Eligibility criteria - adult HNC pts disease-free for 6 months to 3 years following surgery, radiation therapy, and/or chemotherapy. Pts were randomized to 12 weeks of daily Juice-Plus+ capsules or placebo. Pre- and post-treatment oral cavity mucosal biopsies and blood tests were obtained. The study primary endpoint was % expression of the cell cycle regulatory protein p27 by immunohistochemistry in the oral mucosal specimens, a SEB for development of SPT. Secondary endpoints included cell proliferation measured by Ki-67, DNA damage, T-cell function, and serum carotenoid and antioxidant levels. Results: Between 2004-2009, 134 pts were entered (72 on Arm A, 62 on Arm B). Pt characteristics: median age 59, 85% male, 89% White, 62% stage III-IV. Toxicity was negligible. P27 and Ki-67 data was available in 72-78% of pts. There was no significant difference in mean positive p27 protein staining between Arms A and B from baseline (35% in both Arms) to 12 weeks (36.6% in Arm A vs. 36.2% in Arm B, higher is better, p = 0.94). However, more pts in Arm A had grade 3 p27 staining intensity than in Arm B, 7.6% at baseline (both arms) vs. 8.4% in Arm A and 6.3% in Arm B at 12 weeks (p = 0.13). Furthermore, pts in Arm A had slightly lower proliferation rates: 24.1% at baseline (both arms) vs. 22.5% in Arm A and 26.5% in Arm B at 12 weeks (p = 0.12). Four SPT have occurred in Arm A, 8 in Arm B. Conclusions: The p27, Ki-67, and SPT data suggest that patients in Arm A have more favorable results compared to those on Arm B. The remaining data, still under analysis, will be presented at which time the code for Arms A and B (Juice-Plus+ or placebo) will be broken. This study was supported by NSA, Inc. and NIH/NCI grants 3 U10 CA 81851 and R21 CA 106205. No significant financial relationships to disclose.