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.