More on COX-2 inhibitor celecoxib (Celebrex)

[~MaryO~]

U.S. Department of Health and Human Services

 

NATIONAL INSTITUTES OF HEALTH

 

NIH News

 

NIH Office of the Director (OD)

http://www.nih.gov/icd/od/

 

FOR IMMEDIATE RELEASE

Friday, December 17, 2004

 

CONTACT:

John Burklow,

Don Ralbovsky,

Office of Communications and Public Liaison

301-496-5787

 

NIH HALTS USE OF COX-2 INHIBITOR IN LARGE CANCER PREVENTION TRIAL

 

The National Institutes of Health (NIH) announced today that it has suspended the use of COX-2 inhibitor celecoxib (Celebrex TM Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI). The study, called the Adenoma Prevention with Celecoxib (APC) trial, was stopped because analysis by an independent Data Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo.

 

Additional cardiovascular expertise was added to the safety monitoring committees at the request of the Steering Committees for this trial after a September 2004 report that the COX-2 inhibitor rofecoxib (Vioxx TM) caused a two-fold increased risk of cardiovascular toxicities in a trial to prevent adenomas. The APC is a study of more than 2,000 people who have had a precancerous growth (adenomatous polyp) removed. They were randomized to

take either 200 mg of celecoxib twice a day, 400 mg of celecoxib twice a day, or a placebo for three years. The trial began in early 2000 and is scheduled to have been completed by Spring 2005.

 

Investigators at the 100 sites in the APC trial located primarily in the United States, with a few additional sites in the United Kingdom, Australia, and Canada, have been instructed to immediately suspend study drug use for all participants on the trial, although the participants will remain under observation for the planned remainder of the study.

 

"Data from the report on rofecoxib (Vioxx TM) informed us of the need to focus on specific cardiovascular issues, and our Institutes brought in the experts to do so," said Elias A. Zerhouni, M.D., NIH Director. "Our overwhelming commitment is to advance the health and to protect the safety of participants in clinical trials. We are examining the use of these agents in all NIH-sponsored clinical studies. In addition, we are working closely with our colleagues at FDA to ensure that the public has the information they need to make informed decisions about the use of this class of drug."

 

"The rigor of our clinical trials system has allowed us to find this problem," said NCI Director Andrew C. von Eschenbach, M.D. "We have a strong system that provides us with the opportunity to both find ways to effectively treat and prevent disease and to do so in a way that protects the lives and safety of the participants."

 

NIH sponsors over 40 studies using celecoxib for the prevention and treatment of cancer, dementia and other diseases. In light of these new findings, NIH Director Zerhouni requested:

--a full review of all NIH-supported studies involving this class of drug.

 

-- NIH Institutes to inform the principal investigators for all of these studies and will ask them to communicate directly with their study participants and explain the risks and benefits

-- NIH to ask each investigator to inform us of their plan to analyze their data in light of the information

-- the Institutional Review Boards (IRBs) for all related trials to assess the new information and to conduct a safety review as well

 

The NIH comprises the Office of the Director and 27 Institutes and Centers. The Office of the Director is the central office at NIH, and is responsible for setting policy for NIH and for planning, managing, and coordinating the programs and activities of all the NIH components. The NIH, the Nation's medical research agency, is a component of the U.S. Department of Health and Human Services.

 

##

 

------------------------------------

 

 

U.S. Department of Health and Human Services

 

NATIONAL INSTITUTES OF HEALTH

 

NIH News

 

NIH Office of the Director (OD)

http://www.nih.gov/icd/od/

 

National Cancer Institute (NCI)

http://www.nci.nih.gov/

 

 

FOR IMMEDIATE RELEASE

Friday, December 17, 2004

 

CONTACTS:

NIH Press Office

(301) 496-5787

 

NCI Press Office

(301) 496-6641

 

QUESTIONS AND ANSWERS

NIH HALTS USE OF COX-2 INHIBITOR IN LARGE CANCER PREVENTION TRIAL

 

The National Institutes of Health (NIH) announced today that it has suspended the use of COX-2 inhibitor celecoxib (Celebrex TM Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI). The study, called the Adenoma Prevention with Celecoxib (APC) trial, was stopped because analysis by an independent Data Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo. (Press release: http://www.nih.gov/news/pr/dec2004/od-17.htm )

 

Q: WHAT IS NIH DOING IN RESPONSE TO THESE FINDINGS?

 

NIH has halted the use of COX-2 inhibitor celecoxib (Celebrex TM Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial. Additionally, Elias A. Zerhouni, M.D., Director, NIH, has called for an immediate review of the entire grant portfolio for studies using COX-2 inhibitor drugs. NIH is also notifying all principal investigators of the NCI study findings and will ask investigators to inform the agency of their plan to analyze their data in light of this information. In addition, NIH is asking the Institutional Review Boards (IRBs) for all related trials to assess the new information and to conduct a safety review.

 

Q: ARE OTHER NIH STUDIES USING COX-2 INHIBITORS?

 

NIH sponsors more than 40 studies using celecoxib for the prevention and treatment of cancer, rheumatoid and osteoarthritis, dementia and other diseases. NIH's commitment is to advance the health and to protect the safety of participants in clinical trials. The agency is examining the use of these agents in all NIH-sponsored clinical studies. In addition, NIH is working closely with colleagues at FDA to ensure that the public has the

information they need to make informed decisions about the use of this class of drug.

 

Q: WHY HAS NCI BEEN USING COX-2 INHIBITORS IN CLINICAL TRIALS?

 

Numerous compounds are examined by the National Cancer Institute (NCI) for their potential to prevent or treat cancer. One class of compounds, cyclooxygenase (COX) inhibitors, is currently being tested in both prevention and treatment clinical trials. Epidemiologic studies have shown that people who regularly take non-steroidal anti-inflammatory drugs

(NSAIDs), such as aspirin and ibuprofen to treat conditions like arthritis, have lower rates of colorectal polyps, colorectal cancer, and death due to colorectal cancer. NSAIDs block cyclooxygenase enzymes, which are produced by the body when there is inflammation and are also produced by precancerous tissues. Inhibition of COX-2 may help treat and prevent cancer, while inhibition of COX-1 may induce certain medical problems, like stomach bleeding, that occur when NSAIDS are taken regularly for long periods of time.

 

Q: WHAT IS CELEBREX AND WHY HAS NCI USED THIS DRUG IN THEIR TRIALS?

 

Pharmaceutical companies have created NSAIDs that block only COX-2; one of them, celecoxib (Celebrex™), manufactured by Pfizer, Inc., New York, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of both osteoarthritis and adult rheumatoid arthritis (diseases in which the joints are inflamed) in December 1998. Because over a decade of scientific work has suggested the potential of COX-2 inhibitors to prevent and treat cancer, the National Cancer Institute (NCI) has clinical trials under way to look at the efficacy and safety of these drugs.

 

Q: WHAT SPECIFIC TRIALS HAS NCI BEEN CONDUCTING WITH CELEBREX?

 

NCI's Division of Cancer Prevention (DCP) began its studies with celecoxib with a trial in people with Familial Adenomatous Polyposis (FAP). Patients with FAP develop hundreds to thousands of precancerous polyps (adenomas) throughout the colon and rectum. Left untreated, nearly all FAP patients develop colorectal cancer by their 40s and 50s. The primary treatment for FAP is surgical removal of most or all of the colon and rectum with

subsequent surveillance of any remaining colorectal segment. In an NCI-sponsored trial, celecoxib helped reduce the number of colon polyps in patients with FAP. The results of this study were published in the New England Journal of Medicine on June 29, 2000, and led to FDA-approval of celecoxib as an adjunctive drug (an accessory or auxiliary agent) that could be added to the standard of care in people with FAP.

 

As of October 2004, DCP sponsored 23 trials of varying sizes to test the potential of celecoxib to prevent cancer in a number of organ sites. These trials range in size from under 10 participants to more than 2,000 and aim to prevent bladder, breast, cervical, colorectal, esophageal, head and neck, skin, lung, oral, and prostate cancers, as well as multiple myeloma. The majority of these trials are in collaboration with Pfizer, Inc.

 

Additionally, to examine potential benefits of COX-2 inhibitors for the treatment of patients with cancer, NCI's Division of Cancer Treatment and Diagnosis (DCTD) is sponsoring approximately 20 trials of varying sizes with celecoxib. The majority of these studies are small phase I or II clinical trials in cancers such as pancreatic, breast, ovarian, non-small cell lung, and solid tumors. DCTD also is sponsoring two ongoing randomized phase III clinical trials: the first trial compares two chemotherapy agents,

exemestane vs anastrozole, in postmenopausal women with estrogen receptor-positive primary breast cancer; the second trial compares several chemotherapy agents in node-negative breast cancer patients. Both phase III trials randomized women to either those taking celecoxib or not taking celecoxib, in addition to the agents mentioned above.

 

Q: WHAT IS THE STATUS OF THE APC (ADENOMA PREVENTION WITH CELECOXIB) TRIAL?

 

The National Cancer Institute suspended the use of COX-2 inhibitor celecoxib (Celebrex™; Pfizer) on December 17, 2004, for all participants in a large colorectal cancer prevention clinical trial, the Adenoma Prevention with Celecoxib (APC) trial, because analysis by an independent Data Safety Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo. Safety monitoring of a similar study that was sponsored by Pfizer, called the PreSAP cancer trial, did not find an increased risk of

cardiovascular events.

 

Additional cardiovascular expertise was added to the safety monitoring committees at the request of the steering committees for these trials after a September 2004 report that the COX-2 inhibitor rofecoxib (Vioxx™) caused a two-fold increased risk of cardiovascular toxicities in a trial to prevent adenomas. The APC trial is a study of more than 2,000 people who have had a precancerous growth (adenomatous polyp) removed. They were randomized to take either 200 mg of celecoxib twice a day, 400 mg of celecoxib twice a day, or a placebo for three years. The trial began in early 2000 and is scheduled to be completed by spring 2005.

 

Investigators at the 100 sites in the APC trial, located primarily in the United States, with a few additional sites in the United Kingdom, Australia, and Canada, have been instructed to immediately suspend study drug use for all participants on the trial, although the participants will remain under observation for the planned remainder of the study.

 

Q: WHAT ACTIONS IS NCI PLANNING TO TAKE TO NOTIFY PATIENTS ON OTHER COX-2 INHIBITOR CLINICAL TRIALS?

 

NCI will notify all of the principal investigators of its sponsored trials involving COX-2 inhibitors. They will be instructed to notify their institutional review boards, data safety monitoring boards, and participants about this new information. NCI will also require that the informed consent for these trials be revised to reflect this new information and that individuals in the trials be re-consented (asked to sign new consent forms with updated information about risks and benefits of the trials).

 

--------------------------

 

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

 

For more information about regulation of COX-2 inhibitors by the FDA, please visit the FDA Web site at http://www.fda.gov/cder/drug/default.htm .

 

This NIH News Release is available online at:

http://www.nih.gov/news/pr/dec2004/od-17.htm

 

The Questions and Answers regarding this release are available online at:

http://www.nih.gov/news/pr/dec2004/od-17Q&A.htm

 

To subscribe (or unsubscribe) from this list, go to

http://list.nih.gov/cgi-bin/wa?SUBED1=nihpress&A=1.

[~SuziQ~]

I read about this earlier, Mary. Of course I started complaining about Pfizer's stock price dropping again. <_ never mind the fact that i take celebrex. one out of two ain bad. was allergic to vioxx. it will be interesting for me on monday as when see rheumatologist.... he prescribes my from what read though should okay x daily.>

[~MaryO~]

Gee, and I was allergic to the Celebrex! Mever tried the Vioxx, thank goodness. I just went back to my tried-and-true trusty Tomectin.

 

Good luck Monday.