A Randomized Study of Sulindac in Oral Premalignant Lesions

Inclusion Criteria: For this study an Oral Premalignant Lesions (OPL) is defined as a lesion which can include atypical hyperplasia, atypical hyperkeratosis, leukoplakia, and erythroplakia/erythro-leukoplakia. Histology MUST be confirmed by an MSKCC pathologist for all participating sites. An OPL may be located in the oral cavity, oropharynx. The subj has a histologically suspected or confirmed index oral premalignant lesion, 12mm or greater in size that has not been bx'd in the past 6 wks. Each index lesion must be either: An EARLY premalignant lesion defined to be at high risk as indicated by the presence of at least one of the following: atypical cells or mild dysplasia, or hyperplastic leukoplakia of high-risk sites, lateral and ventral tongue and floor or mouth OR An ADVANCED premalignant lesion defined as the presence of at least one of the following: moderate dysplasia or severe dysplasia (excluding CIS) The subj is > 18 yrs of age The subj's life expectancy is > 12 wks and Zubrod performance status is 0 or 1 (Appendix VIII). The subj meets the following lab eligibility criteria during a time not to exceed 4 wks prior to randomization. Hemoglobin level above 10g/dL for women and above 12g/dL for men. WBC count > 3,000 uL. Platelets count > 125,000 uL. Total bilirubin < or = 1.5xULN AST (SGOT) and ALT (SGPT) < or = 2.5 x ULN. BUN and serum creatinine < or = 1.5 x ULN. If the subj is female and of childbearing potential (women are considered not of childbearing potential if they are at least 2 yrs postmenopausal and/or surgically sterile), she: has been using adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) since her last menses and will use adequate contraception during the study, AND is not lactating, AND has a documented negative serum pregnancy test within 14 ds prior to randomization. The subj's history/use of NSAIDs, aspirin, corticosteroids meets the following criteria: total oral/intravenous corticosteroid use has been < 14 ds within 6 mos of the Baseline visit, and total inhaled corticosteroid use has been < 30 ds within 6 mos of the Baseline visit, and is willing to limit aspirin use to < or = 120 mg po per d (typical cardioprotective dose in India) or < or = 80 mg po per d (typical cardioprotective dose in the US) for the duration of the study, and is willing to abstain from chronic use of all NSAIDs and COX-2 inhibitors for duration of study. Chronic use of NSAIDs is defined as a frequency of > or = 3 times/wk AND for more than a total of 14 ds a yr. The subj has discontinued any other chemopreventive therapy at least 3 mos prior to the Baseline visit and all toxicities have been fully resolved. If applicable, the subj has been counseled on smoking cessation. If the subject is male, will use adequate contraception during the study. Exclusion Criteria: The subject has had chemotherapy, immunotherapy, hormonal tx (other than HRT for menopause), or RT within 3 wks of the Baseline visit. The subj has not recovered from the acute toxic effects of chemotherapy, immunotherapy, hormonal tx, or RT. The subj will need concurrent chemotherapy, radiotherapy, hormonal (other than HRT for menopause), or immunotherapy during the time of study. The subj has a history of hypersensitivity to sulindac, COX-2 inhibitors, NSAIDs, salicylates. The subj has been diagnosed with or has been treated for esophageal, gastric, pyloric channel, or duodenal ulceration. The subj has a history of inv cancer within the past 1 yr (excluding non-melanoma skin cancer and in situ cervical cancer). The subj has a chronic or acute renal or hepatic disorder or a significant bleeding disorder or any other condition which, in the Institutional Principal Investigator's opinion, might preclude study participation. The subj has a past history of or active inflammatory bowel disease (eg. Crohn's disease or ulcerative colitis) or pancreatic disease. The subj has received any investigational medication within 30 ds of the Baseline visit or is scheduled to receive an investigational drug during the course of the study. The subj is, in the opinion of the Institutional Principal Investigator, not an appropriate candidate for study participation. The subj participated in the study previously and was withdrawn.