"Celecoxib (Celebrex) May Foil Recurrent Prostate Cancer: Presented at ACS"
By Mike Fillon
NEW ORLEANS, LA -- October 13, 2004 – Celecoxib (Celebrex), a commonly prescribed anti-inflammatory drug, might slow progression of recurrent prostate cancer, according to results of a study presented here on October 10[th at the American College of Surgeons 90th Annual Clinical Congress.
The researchers say this is the first time a cyclooxygenase 2 (COX-2) inhibitor, in this case, celecoxib, has been shown to have a therapeutic effect in prostate cancer at any stage of the disease.
"The potential for anti-inflammatory medicines to have an antitumor effect has been observed for some time. We're just at the beginning of understanding the possibilities," said Raj Pruthi, MD, Assistant Professor of Surgery/Urology, University of North Carolina, Chapel Hill.
Dr. Pruthi presented the results on behalf of the research team, led by J. Eric Derksen, MD, also of University of North Carolina at Chapel Hill, during the Forum on Fundamental Surgical Problems focusing on Urological/Reproductive Surgery.
Results of the study showed that levels of prostate specific antigen (PSA) stabilized, were maintained, or declined in 92% of 24 men who took celecoxib twice a day for a year. Dr Pruthi said the COX-2 enzyme is involved in prostaglandin synthesis, cell proliferation, and angiogenesis in a variety of disease processes.
Although 71% of the men in the study had a moderate or high increase in PSA levels before treatment, after 3 months of treatment with celecoxib 400 mg or 800 mg twice a day 92% of men had a slow rate of increase, maintained their levels or had a decrease in their levels. At the end of a year of therapy, one man (4%) had a high rate of increase of PSA, and three (13%) had a moderate rise in PSA. The remaining 83% of men had slow rate of increase, stable levels, or decreased levels.
Other investigators are studying the use of COX-2 inhibitors as antitumor medications for a variety of cancers. According to Dr. Pruthi, the National Cancer Institute sponsored 13 studies on the use of COX-2 inhibitors for colon, prostate, and breast cancer in 2003 and 34 in 2004 on cancers of the head and neck, lung, and bladder.
Interest in COX-2 inhibitors as a potential cancer treatment is increasing because of their ability to interfere with the body's repair mechanism, which is out of control in the presence of cancer. "The COX-2 enzyme is not normally expressed in the body," said Dr. Pruthi. "But if there is illness or injury, the body begins to produce COX-2 to increase blood flow, create inflammation, and promote epithelial cell growth that will help it heal."
Dr. Pruthi added that the same processes occur in tumor development -- excessive cell growth, angiogenesis (blood vessel generation), and excessive inflammation with cellular mediators and growth factors. "Drugs that inhibit COX-2 appear to work to prevent angiogenesis and to promote apoptosis (natural programmed cell death)."
Dr. Pruthi said the potential role of COX-2 inhibitors in men with prostate cancer is supported by large-scale epidemiological investigations as well as animal studies. Population studies have shown that men who take anti-inflammatory drugs have less than half the risk of developing prostate cancer than men who don't take these drugs. In animal experiments, prostate tumors have shrunk in size by a factor of 10 after being exposed to a COX-2 inhibitor.
Dr. Pruthi said his team is testing celecoxib in other groups of men with prostate cancer. He is planning a study of the drug as adjuvant therapy in men with advanced disease as well as those at high risk for recurrence immediately after surgery.
"The studies haven't been done yet, but it is interesting to think about giving a COX-2 inhibitor to men with advanced disease who were not successfully treated with hormonal therapy. Those are the worst of the worst cases of prostate cancer patients," said Dr. Pruthi. "Even more exciting is to contemplate using the drug as a chemopreventive agent, before a man even gets prostate cancer."
Pfizer Inc. provided the drug used in this study.
[Presentation title: "A Phase II Trial of Celecoxib in PSA Recurrent Prostate Cancer After Definitive Radiation Therapy (XRT) or Radical Prostatectomy (RP)." Session code SF-UR]
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