1. Celecoxib Therapy For RRP Dr. Bettie Steinberg, Dr. Allan Abramson, Dr. Mark Shikowitz LIJ Medical Center Dr. Richard Smith, Dr. Harry Hoffman - Univ. Iowa Dr. Mark Courey – Univ. California, San Francisco Dr. Craig Derkay, Dr. John Sinacori – Eastern Virginia Medical School Dr. Glenn Peters, Dr. Paul Castellanos – Univ. Alabama, Birmingham Dr. Clark Rosen, Univ. Pittsburgh

2. Cyclooxygenase (COX-2) Enzyme elevated in inflammation Also elevated in many premalignant and malignant tumors – Colorectal polyps – Respiratory papillomas – Head and neck cancer – Breast cancer – Lung cancer – Cervical cancer – Prostate cancer Inhibiting COX-2 helps other types of tumors

3. COX-2 Activities Arachidonic Acid PGG 2 PGH 2 PGD 2 PGE 2 PGF 2a PGI 2 TXA 2 COX-2 angiogenesis, apoptosis, immune surveillance, differentiation

4. COX-2 and Its Product PGE 2 Are Expressed in Respiratory Papillomas COX-2 Neg control NormalPapilloma Relative COX-2 levels Normal Papilloma * 0 1 2 3 4 5 6 * 0 50 100 150 200 250 300 * Normal Papilloma PGE 2 (pg/ml) COX-2 NPNP PCon

5. Inhibiting COX-2 Reduces Papilloma Cell Proliferation and Increases Apoptosis * p < 0.05 ** p < 0.01

6. 36912151821240 Months after randomization Growth Rate 36912151821240 Months after randomization Growth Rate 36912151821240 Months after randomization Growth Rate Three Patients Treated in Pilot Study All Free of Disease 12 months 18 months Trachea, Patient 3

7. New NIH Grant To Study Efficacy of Celebrex 5 year grant Enrolling patients beginning of year Grant will pay for patient travel to one of participating centers Celebrex provided by Pfizer at no cost Grant will permit us to determine whether Celebrex is an effective therapy for RRP, and if some patients respond and others do not, why

8. Eligibility Age 4 years or older 3 or more surgeries in past year or tracheal/ broncheal involvement No history of heart disease or current high blood pressure No significant kidney or liver disease Not allergic to Celebrex or sulfa drugs

9. Clinical Celecbrex Trial Study Design Celebrex Placebo Pre Treat Randomize 6 months 12 months Everyone gets Celebrex Study lasts 30 months for each patient Surgery every 3 months during the study, unless free of disease, then office evaluations every three months Blood tests every three months, at time of surgery, to help determine mechanism of response

10. If Interested in Participating Send patient records to: Dr. Allan Abramson or Dr. Mark Shikowitz Department of Otolaryngology Long Island Jewish Medical Center 270-05 76 th Ave New Hyde Park, NY 11040 Tel: 718-470-7550