Celebrex and Prostate Cancer
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From: Lyman on 5 Mar 2006 20:30 An Anti-Inflammatory Drug (Celebrex) Slows Progression in Men with Recurrent Prostate Cancer October 18, 2004 - New Orleans - A small study is the first to show that Celebrex, an anti-inflammatory pain killer, slows the progression of recurrent prostate cancer. The study was presented earlier this month at the 2004 annual Clinical Congress of the American College of Surgeons. The trial did not measure any effect on prostate cancer tumors. But in a small group of men experiencing rising prostate specific antigen levels following primary treatment (a condition known as "biochemical recurrence"), Celebrex slowed, stabilized or reduced the level of PSA. In this study, 24 men took the Celebrex twice a day for a year. Twenty-two of the men showed some positive effect. "This is the first report of a Cox-2 inhibitor having a therapeutic effect in prostate cancer at any stage of the disease," Raj Pruthi, MD, FACS, assistant professor of surgery, University of North Carolina, Chapel Hill, said. Oct 18, Pfizer, maker of Celebrex, announced a new clinical trial to find out whether Celebrex has any cardiovascular side effects. For more information see related news linkbelow. Although the rate of increase of PSA was moderate or high in 17 of the men in the study before treatment, it was slow, stable, or decreased in 22 men who received 400 mg or 800 mg of celecoxib twice a day for three months. At the end of a year of therapy, only one man had a high rate of increase of PSA, and three had a moderate rise in PSA. The remaining 20 men had delayed, stable, or decreased PSA levels. Cox-2 inhibitors as antitumor medications are being studies by other investigators as treatment for a variety of cancers. According to Dr. Pruthi, thirteen National Cancer Institute (NCI)-sponsored studies began exploring Cox-2 inhibitors for colon, prostate, and breast cancer in 2003 and 34 NCI-studies started looking at these drugs for cancers of the head and neck, lung, and bladder in 2004. Interest in Cox-2 inhibitors as a potential cancer treatment is increasing because of its ability to interfere with the body's repair mechanism, which is out of control in the presence of cancer. Cox-2 inhibitors interfere with the action of cycloxygenase-2, an enzyme involved in prostaglandin synthesis, cell proliferation, and angiogenesis in a variety of disease processes. "The Cox-2 enzyme is not normally expressed in the body. 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. 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]," Pruthi said. Pruthi and his colleagues are beginning to test the Cox-2 inhibitor 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 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. In animal experiments, prostate tumors have shrunk in size by a factor of ten after being exposed to a Cox-2 inhibitor, Pruthi said. "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," he concluded. J. Eric Derksen, MD and Eric Wallen, MD, FACS, joined Dr. Pruthi in the study of celecoxib in men with recurrent prostate cancer.
From: Lyman on 5 Mar 2006 20:37 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 10th 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]
From: Lyman on 5 Mar 2006 20:41 Celebrex Bests Vioxx as Potential Cancer Fighter Despite cardiovascular risks, painkiller appears to block key protein for cancer cell replication By Steven Reinberg HealthDay Reporter TUESDAY, March 1 (HealthDayNews) -- Celebrex, one of the cox-2 painkillers under fire for increasing heart attack and stroke risk, may actually slow certain cancers in a way that its cousin, Vioxx, does not, according to new preliminary research. Both drugs, known as cox-2 inhibitors, have already been shown to inhibit the growth of tumors that depend on the cox-2 enzyme, as happens with some prostate and breast cancers. Related Stories ? Virus May Have Links to Prostate Cancer ? Age Could Alter PSA Readings ? Antioxidant Supplements Don't Protect Against Prostate Cancer Related Videos Injections Help Enlarged Prostate Extending Lives For Prostate Cancer Biothermy For Prostate Cancer Related Slides Benign Prostate Hyperplasia Prostate Cancer But a new study finds that Celebrex (celecoxib) appears to fight prostate cancer on another front, by blocking a key protein that is essential to the replication of cancer cells. This latest report appears in the March 1 issue of Clinical Cancer Research. "Celecoxib can mediate anti-tumor effects by mechanisms in addition to targeting cox-2, which is its known target," said lead researcher Dr. Andrew Dannenberg, director of cancer prevention at the Weill Medical College of Cornell University in New York City. "This suggests that the agent's overall anticancer activity may reflect cox-2 inhibition and other properties." In their study, Dannenberg's team treated human prostate cancer cells that did not have the cox-2 enzyme with Celebrex. The researchers found that cells treated with the drug did not reproduce as quickly as similar untreated cells. Further research determined that Celebrex was blocking cyclin D1. "We were able to demonstrate that at clinically achievable concentrations of the drug in cells that don't express cox-2, the drug still has activity," Dannenberg said. "Based on these results, it's conceivable it will have effects in human tumors that do or do not express cox-2," he added. However, when the researchers tried the same experiment using Vioxx, they found the cancer cells continued to reproduce. "This makes the point that all cox-2 inhibitors are not created equal," Dannenberg said. They were, however, given equal treatment two weeks ago, when a U.S. Food and Drug Administration advisory panel voted to recommend that Celebrex, Vioxx and Bextra stay on the market, while acknowledging the cardiovascular dangers of the drugs. On Tuesday, the Louisiana health department announced it will impose additional safeguards, which will go into effect on March 15. Those safeguards will require doctors to supply a diagnosis code for every prescription for both Celebrex and Bextra, telling the pharmacist why the patient needs the medication. Vioxx is not affected because it was removed from pharmacy shelves last fall by its manufacturer after trials revealed the heart risks. Despite the concerns about the cardiac risk of cox-2 inhibitors, Dannenberg believes that when it comes to cancer, the considerations of these drugs' ability to fight tumors should be the first priority. "Cox-2 inhibitors have been shown to have a small increase in risk of cardiovascular complications when taken long term," Dannenberg noted. "However, it is extremely important in the oncology world to recognize that efficacy is of greater concern. This new study makes the observation that celecoxib can act by more than a single mechanism to inhibit tumor growth." Dannenberg noted that his work is not a clinical study, and that the use of Celebrex in fighting cancer needs to wait for the outcome of several ongoing clinical trials. "Decision-making on clinical use should be based on the results of these clinical trials," he said. Another expert thinks that much more needs to be done before Celebrex can find a role in fighting cancer. "It is surprising to me that the authors did not try to see what would happen to these cells when treated with aspirin or one of the inhibitors which block cox-1 specifically, since these cells did express cox-1," said Dr. Raymond N. DuBois, the director of the Vanderbilt-Ingram Comprehensive Cancer Center at Vanderbilt University. "We have found that some ovarian cancer cells are very dependent on cox-1 expression, and respond very well to cox-1 inhibitors," DuBois added. DuBois noted that in the study, higher doses of Celebrex seemed to be more effective. "Unfortunately, these higher doses in humans seem to be associated with adverse cardiovascular effects," he added. "Thus, these selective inhibitors may have some role in treatment of prostate cancer, but their long-term use for prevention at these higher doses may not be well-tolerated." One heart expert said he thought that the use of cox-2 inhibitors to fight cancer was a tricky matter. "We currently do use many drugs for cancer treatment that are themselves toxic to the heart," said Dr. Scott D. Solomon, director of noninvasive cardiology at Brigham and Women's Hospital, in Boston. "Ultimately, I believe we will need large clinical trials to sort this out, with longer follow-up times, since a large enough trial should provide the 'net' between efficacy and safety." Moreover, Solomon is concerned with the ultimate benefit to patients. "Another thing to remember, though, is whether a reduction in cancer cell proliferation as suggested here will result in net benefit to the patient, such as longer life," he said. "This will be necessary to offset any potential increased cardiovascular risk. In short, this is simply more information to fill out our current knowledge of the possible benefits of cox-2 inhibitors." More information The American Cancer Society can tell you more about new cancer treatments ( www.cancer.org target =_new). SOURCES: Andrew Dannenberg, M.D., director, cancer prevention, Weill Medical College of Cornell University, New York City; Raymond N. DuBois, M.D., Ph.D., director, Vanderbilt-Ingram Comprehensive Cancer Center, B.F. Byrd Jr., professor, molecular oncology, medicine, cancer biology and cell-developmental biology, Vanderbilt University Medical Center, Nashville, Tenn.; Scott D. Solomon, M.D., director, noninvasive cardiology, Brigham and Women's Hospital, and associate professor, medicine, Harvard Medical School, Boston; March 1, 2005, Clinical Cancer Research Copyright ? 2005 ScoutNews LLC. All rights reserved. Last updated 3/1/2005
From: Lyman on 5 Mar 2006 20:54 Celebrex provides a two pronged attack against prostate cancer PHILADELPHIA--Celecoxib, a selective COX-2 inhibitor with promising anti-cancer properties, has now been found to attack prostate cancer cells in a second way that differs from Vioxx (rofecoxib), another anti-inflammatory drug that also inhibits COX-2. In studies published in the March 1 issue of the journal Clinical Cancer Research, scientists at the Weill Medical College of Cornell University revealed that celecoxib, marketed under the name Celebrex, not only targets COX-2, but also reduces levels of a key protein, cyclin D1, that's critical for cell replication. "It is well established that COX-2 is a significant and rational target for anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer prevention at the Weill Medical College of Cornell University and senior author of the paper. "These studies suggest that celecoxib exerts a second mode of action independent of its known anti-inflammatory mechanism that imposes further restrictions on the proliferation of prostate cancer cells. The results provide potentially important insights into our understanding of the overall anti-tumor activity of selective COX-2 inhibitors." Dannenberg and a team of investigators discovered this new mechanism by applying celecoxib to prostate cancer cells that failed to express COX-2. Here, the scientists observed that the celecoxib-treated cancer cells did not replicate as rapidly as untreated cells. After further analysis, they found the drug worked by suppressing amounts of cyclin D1, a protein that's essential if cells are to grow, divide and spread. The scientists also attempted to replicate the experiment with Vioxx substituting for celecoxib. In this case, the prostate cancer cells continued to flourish. "These results support the notion of a unique action by celecoxib that is independent of COX-2, and that's different from Vioxx," said Dannenberg. "These beneficial effects were observed at concentrations of celecoxib that occur in humans," added Dannenberg. "This increases the likelihood that our findings are clinically relevant." Dannenberg and his colleagues then demonstrated that celecoxib worked in animals that served as hosts for human prostate tumors. In this animal model, celecoxib not only was shown to reduce proliferation of cancer cells, but also reduced the growth of blood vessels at the tumor sites. As a result, tumor mass and blood vessel density in the treated animals was about half that observed in the untreated animals. Contributing to the studies, along with Dannenberg, were Kotha Subbaramaiah, Baoheng Du and Mindy Chang from Weill Medical College of Cornell University, New York, N.Y.; Manish Patel, Carlos Cardon-Cardo, and Howard Thaler, Memorial Sloan-Kettering Cancer Center, New York, N.Y.; and Peiying Yang and Robert Newman, UT M.D. Anderson Cancer Center, Houston, Texas.
From: Lyman on 5 Mar 2006 20:38
Celebrex Provides A Two Pronged Attack Against Prostate Cancer PHILADELPHIA -- Celecoxib, a selective COX-2 inhibitor with promising anti-cancer properties, has now been found to attack prostate cancer cells in a second way that differs from Vioxx (rofecoxib), another anti-inflammatory drug that also inhibits COX-2. In studies published in the March 1 issue of the journal Clinical Cancer Research, scientists at the Weill Medical College of Cornell University revealed that celecoxib, marketed under the name Celebrex, not only targets COX-2, but also reduces levels of a key protein, cyclin D1, that's critical for cell replication. "It is well established that COX-2 is a significant and rational target for anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer prevention at the Weill Medical College of Cornell University and senior author of the paper. "These studies suggest that celecoxib exerts a second mode of action independent of its known anti-inflammatory mechanism that imposes further restrictions on the proliferation of prostate cancer cells. The results provide potentially important insights into our understanding of the overall anti-tumor activity of selective COX-2 inhibitors." Dannenberg and a team of investigators discovered this new mechanism by applying celecoxib to prostate cancer cells that failed to express COX-2. Here, the scientists observed that the celecoxib-treated cancer cells did not replicate as rapidly as untreated cells. After further analysis, they found the drug worked by suppressing amounts of cyclin D1, a protein that's essential if cells are to grow, divide and spread. The scientists also attempted to replicate the experiment with Vioxx substituting for celecoxib. In this case, the prostate cancer cells continued to flourish. "These results support the notion of a unique action by celecoxib that is independent of COX-2, and that's different from Vioxx," said Dannenberg. "These beneficial effects were observed at concentrations of celecoxib that occur in humans," added Dannenberg. "This increases the likelihood that our findings are clinically relevant." Dannenberg and his colleagues then demonstrated that celecoxib worked in animals that served as hosts for human prostate tumors. In this animal model, celecoxib not only was shown to reduce proliferation of cancer cells, but also reduced the growth of blood vessels at the tumor sites. As a result, tumor mass and blood vessel density in the treated animals was about half that observed in the untreated animals. Contributing to the studies, along with Dannenberg, were Kotha Subbaramaiah, Baoheng Du and Mindy Chang from Weill Medical College of Cornell University, New York, N.Y.; Manish Patel, Carlos Cardon-Cardo, and Howard Thaler, Memorial Sloan-Kettering Cancer Center, New York, N.Y.; and Peiying Yang and Robert Newman, UT M.D. Anderson Cancer Center, Houston, Texas. ### Founded in 1907, the American Association for Cancer Research is a professional society of more than 24,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meeting attracts more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research. .. |