Pilot study of celecoxib in oral premalignant lesions (OPLs): Preliminary results.

1025 Background: 10-44% of patients with OPLs will be diagnosed with squamous cell carcinomas of the head and neck (SCCHNs) over 5-10 years. Cyclooxygenase-2 (COX-2) is progressively upregulated in SCCHN tumorigenesis, and is associated with the malignant phenotype. Preclinical data shows that COX-2 inhibition suppresses tumorigenesis.,This phase II study investigated effects of celecoxib on surrogate endpoint biomarkers (SEBs) in 20 patients with OPLs. Oral mucosa prostaglandin E2 (PGE2) levels in post- vs. pre-treatment samples is the primary SEB. Other SEBs include Ki67, microvessel density and histology. Eligibility requirements included OPL, no tobacco for ≥ 1 month, and no contraindication to celecoxib. Pre- and post-treatment biopsies after 3 months (mos) of celecoxib (400 mg BID) were done. Half the specimen was frozen at -70 C and half formalin-fixed, paraffin-embedded for H&E and immunohistochemistry. PGE2 levels were determined by enzyme immunoassay. Subjects with ≥ 30% decrease in the OPL, ≥ 30% decrease in PGE2 and/or improvement in histology stayed on celecoxib for 12 mos, when biopsies were repeated.,18 patients are evaluable at 3 mos, 10 at 12 mos. One patient was withdrawn for gr 2 allergic reaction. Celecoxib was otherwise well-tolerated. At 3 mos, 10/17 had ≥ 30% decrease in PGE2, median = -40.8% (p=0.04). 2 patients were taken off study at 3 mos, as criteria for continuation were not met. One patient voluntarily withdrew due to gr 1 dyspepsia. At 12 mos, 6/10 had ≥ 30% decrease in PGE2, median = -41.8% (p>0.05). Table 1 shows other SEB results. No subjects developed invasive carcinoma since enrolling.,Treatment with celecoxib was well-tolerated, and appears associated with favorable PGE2 modulation. This appears sustained in some but not all patients at 12 mos. Preliminary data suggest celecoxib has promising activity in suppressing SCCHN tumorigenesis in at-risk patients. [Figure: see text] No significant financial relationships to disclose.