Neoadjuvant erlotinib, erlotinib-sulindac, or placebo: A randomized, double-blind biomarker modulation study in operable head and neck squamous cell carcinoma (HNSCC).

6051 Background: The epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) pathways are upregulated in HNSCC. Crosstalk potentiates growth, proliferation and invasion. Preclinical models show synergistic anti-tumor effects from dual blockade. We evaluated biomarker modulation in paired tumor specimens from a 3-arm phase 0 trial of erlotinib, a small molecule EGFR inhibitor; erlotinib + sulindac, a non-selective COX inhibitor; vs. placebo. Methods: Patients (pts) with untreated stage II-IVb HNSCC were randomized 5:5:3 to neoadjuvant erlotinib 150 mg daily (Arm 1, n = 19), erlotinib + sulindac 150 mg twice daily (Arm 2, n = 16), or placebo (n = 12). Pts were treated for 7-14 days. Tumor specimens were collected pre- and post-treatment. The primary endpoint was change in Ki-67 proliferative index. We hypothesized an ordering in Ki-67 down-modulation, with Arm 2 u003e Arm 1 u003e placebo. A Jonckheere-Terpstra test evaluated trend; a Wilcoxon test was applied to pairwise contrasts. We prepared tissue m...