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

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

COX-2 Activities

Arachidonic Acid

PGG2

PGH2

PGD2 PGE2 PGF2a PGI2 TXA2

COX-2

COX-2

angiogenesis, apoptosis, immune surveillance, differentiation

COX-2 and Its Product PGE2 Are Expressed in Respiratory Papillomas

COX-2

Neg control

Normal Papilloma

Rel

ativ

e C

OX

-2 le

vels

Normal Papilloma

*

0

1

2

3

4

5

6 *

0

50

100

150

200

250

300*

Normal Papilloma

PG

E2 (

pg/m

l)

COX-2N P N P P Con

Inhibiting COX-2 Reduces Papilloma Cell Proliferation and Increases Apoptosis

R

elat

ive

Pro

lifer

atio

n

Celecoxib (µM)

*

0 2.5 5.0 7.5

*

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Normal

Papilloma

Rel

ativ

e A

popt

osis

Lev

els

*

*

* *

*

0 2.5 5 7.5

Celecoxib (µM)

*

* *

*

0

1

2

3

4

5

6

* p < 0.05** p < 0.01

0

0.02

0.04

0.06

0.08

0.1

3 6 9 12 15 18 21 240

Months after randomization

Gro

wth

Rat

e

0

0.02

0.04

0.06

0.08

0.1

3 6 9 12 15 18 21 240

Months after randomization

Gro

wth

Rat

e

0

0.02

0.04

0.06

0.08

0.1

3 6 9 12 15 18 21 240Months after randomization

Gro

wth

Rat

eThree Patients Treated in Pilot Study

All Free of Disease

12 months 18 months Trachea, Patient 3

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

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

Clinical Celecbrex Trial Study Design

Celebrex

CelebrexPlacebo

Placebo

Pre Treat

Randomize

6 months12 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

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 76th Ave

New Hyde Park, NY 11040

Tel: 718-470-7550