celecoxib, Celebrex
Celecoxib can prevent tumor growth and distant metastasis in postoperative setting.

Roh JL, Sung MW, Park SW, Heo DS, Lee DW, Kim KH.

Department of Otolaryngology--Head and Neck Surgery and Cancer Research Institute, College of Medicine, Chungnam National University, Daejeon, South Korea.

Much evidence suggests that an inflammatory condition provides a microenvironment favorable for tumor growth. One of the main components in the healing wound is the induction of cyclooxygenase-2 (COX-2) and prostaglandins, and many solid tumors have been known to overexpress COX-2. The present study investigated the relationship between surgical wounds and tumor growth and the roles of COX-2 and inflammatory reaction in this microenvironment. We created surgical wounds in syngeneic mice for the implantation of SCC VII murine cancer cell line. Accelerated tumor growth and increased angiogenesis by surgical wounds were clearly observed in C3H/HeJ mice with SCC VII tumor. The COX-2 expression of peritumoral tissues and leukocyte infiltration partly explained the accelerated tumor growth, especially in the early phase after surgical wounding. Celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in tumor-implanted mice with surgical wounds. This tumor-suppressive action of celecoxib did not show any noticeable side effects on the late wound healing and on the gastrointestinal tracts. Prophylactic use of the drug can be advocated in many clinical situations, such as residual tumors or contamination of surgical fields by tumor cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15126364&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Comparison of changes in blood pressure measurements and antihypertensive therapy in older, hypertensive, ambulatory care patients prescribed celecoxib or rofecoxib.

Nietert PJ, Ornstein SM, Dickerson LM, Rothenberg RJ.

Center for Health Care Research, Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. nieterpj musc.edu

STUDY OBJECTIVE: To determine if changes in blood pressure and changes in class or dosing of antihypertensive drugs were significantly different in patients treated with celecoxib versus rofecoxib, two cyclooxygenase (COX)-2 inhibitors. DESIGN: Retrospective cohort study. SETTING: Thirty-one ambulatory care practices that shared an electronic medical record. PATIENTS: Nine hundred sixty men and women over age 55 years with stable hypertension. INTERVENTION: Patients had to have at least a 30-day supply of celecoxib or rofecoxib (any dose) prescribed between July 1, 1999, and June 30, 2000. MEASUREMENTS AND MAIN RESULTS: Patients were followed for 6 months, and logistic regression and survival models were used to compare outcomes between groups while adjusting for confounders. Baseline characteristics of 517 patients receiving celecoxib and 443 receiving rofecoxib were similar. No significant differences were observed, regardless of the COX-2 inhibitor prescribed, in the proportion of patients whose systolic blood pressure increased by 20 mm Hg, whose diastolic blood pressure increased by 15 mm Hg, or who were prescribed a new class of antihypertensive drug. Compared with patients taking celecoxib, those taking rofecoxib were significantly more likely (odds ratio 1.68, 95% confidence interval 1.09-2.60) to have had the dosage of their antihypertensive drug increased and also the dosage increased sooner (p<0.05). New-onset cardiac and renal comorbidity, number of physician visits, and changes in body weight and laboratory values were not significantly different between the groups. CONCLUSION: No significant differences in blood pressure changes or in the proportion of patients who were prescribed a new class of antihypertensive drug were found between rofecoxib- and celecoxib-treated patients. However, significantly more rofecoxib-treated patients had the dosage of their existing antihypertensive drug increased compared with those receiving celecoxib.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14620388&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Suppression of prostate carcinogenesis by dietary supplementation of celecoxib in transgenic adenocarcinoma of the mouse prostate model.

Gupta S, Adhami VM, Subbarayan M, MacLennan GT, Lewin JS, Hafeli UO, Fu P, Mukhtar H.

Department of Urology, The James and Eilleen Dicke Research Laboratory, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.

Epidemiological studies and clinical observations suggest that nonsteroidal anti-inflammatory drugs and certain selective cyclooxygenase (COX)-2 inhibitors may reduce the relative risk of clinically evident prostate cancer. This prompted us to investigate the chemopreventive potential of celecoxib, a selective COX-2 inhibitor, against prostate carcinogenesis in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Similar to prostate cancer in humans, prostate malignancies in TRAMP mice progress from precursor intraepithelial lesions, to invasive carcinoma that metastasizes to lymph nodes, liver, lungs, and occasionally to bone. The basal enzyme activity and protein expression of COX-2 is significantly higher (>4-fold) in the dorsolateral prostate of TRAMP mice up to 24 weeks of age compared with their nontransgenic littermates. Eight-week-old TRAMP mice were randomly divided and fed either control diet (AIN 76A) or a custom prepared AIN 76A diet containing 1500-ppm celecoxib ad libitum for 24 weeks, a dosage that would compare with the normal recommended dose for the treatment of human disease. Studies from two independent experiments, each consisting of 10 mice on test, showed that the cumulative incidence of prostate cancer development at 32 weeks of age in animals fed with AIN 76A diet was 100% (20 of 20) as observed by tumor palpation, whereas 65% (13 of 20), 35% (7 of 20), and 20% (4 of 20) of the animals exhibited distant site metastases to lymph nodes, lungs, and liver. Celecoxib supplementation to TRAMP mice from 8-32 weeks of age exhibited significant reduction in tumor development (5 of 20) with no signs of metastasis. Celecoxib feeding resulted in a significant decrease in prostate (56%; P < 0.0003) and genitourinary weight (48%; P < 0.008). Sequential magnetic resonance imaging analysis of celecoxib-fed mice documented lower prostate volume compared with the AIN 76A-fed group. Histopathological examination of celecoxib-fed animals showed reduced proliferation, and down-modulation of COX-2 and prostaglandin E2 levels in the dorsolateral prostate and plasma, respectively. These results correlated with retention of antimetastasis markers, viz E-cadherin, and alpha- and beta-catenin, along with a significant decrease in vascular endothelial growth factor protein expression. Celecoxib supplementation also resulted in enhanced in vivo apoptosis in the prostate as monitored by several techniques including a recently perfected technique of 99mTc-labeled annexin V in live animals followed by phosphor imaging. One striking observation in an additional study was that celecoxib feeding to mice with established tumors (16 weeks of age) significantly improved their overall survival (P = 0.014), compared with AIN 76A-fed group. Our findings suggest that celecoxib may be useful in chemoprevention of prostate cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15126378&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin.

Brinker A, Goldkind L, Bonnel R, Beitz J.

Division of Drug Risk Evaluation, Office of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20875, USA. brinkera cder.fda.gov

BACKGROUND AND OBJECTIVE: Data on file with the US FDA, and other published studies, suggest that the selective cyclo-oxygenase (COX)-2 inhibitor NSAID rofecoxib has a greater hypertensive adverse effect than other NSAIDs, including celecoxib. In this study we describe a pharmacoepidemiologic analysis of spontaneous adverse event reports of acute, clinically serious hypertension (as defined by hospitalisation) reported in association with rofecoxib, celecoxib, nabumetone and oxaprozin. The objective of this analysis is to assess whether postmarketing data are consistent with results of clinical trials. We also collapse cases into series for the identification of possible risk factors for clinically severe, NSAID-associated hypertension. METHODS: Domestic (US) cases of apparently unconfounded, acute hypertension leading to hospitalisation were collected and reviewed from the spontaneous adverse events database of the FDA for rofecoxib, celecoxib, nabumetone and oxaprozin for the initial 3 years of marketing. Drug use data for the same intervals enabled calculation of reporting rates. RESULTS: In an analysis of reporting rates, hospitalisation for acute blood pressure (BP) elevation was reported more frequently (3.8-fold) for rofecoxib compared with celecoxib. A total of 34 cases are collapsed into case series. No cases were identified for either nabumetone or oxaprozin. Inspection of reviewed cases for celecoxib and rofecoxib suggest that these patients (average age 72 years) were potentially high-risk candidates for NSAID therapy. DISCUSSION AND CONCLUSION: During early marketing, hospitalisation for acute BP elevation appears to have been reported more frequently for rofecoxib compared with celecoxib. This is consistent with clinical trial data on file with the FDA, and other published studies that found rofecoxib to have a greater effect on BP than other NSAIDs, including celecoxib. This finding may be particularly relevant in older patients given the prevalence of hypertension and cardiovascular disease in this age group. Copyright 2004 Adis Data Information BV

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15132714&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Drug switching patterns among patients with rheumatoid arthritis and osteoarthritis using COX-2 specific inhibitors and non-specific NSAIDs.

Zhao SZ, Wentworth C, Burke TA, Makuch RW.

Pharmacia Global Health Outcomes, Peapack, NJ, USA.

PURPOSE: To compare RA and OA patients' time-to-switch after newly initiating treatment with three most commonly used non-specific (NS)-NSAIDs and two COX-2 inhibitors, celecoxib and rofecoxib. METHODS: Managed care enrollees newly prescribed celecoxib, rofecoxib, ibuprofen, naproxen or diclofenac were identified. Time to switch to a different NS-NSAID or COX-2 specific inhibitor was determined using time-to-event analysis and Cox proportional hazards models were used to estimate the odds ratio (OR) after controlling for potential confounders. RESULTS: The time to 25% of the cohort switching was longer for rofecoxib and celecoxib (159 and 205 days respectively) compared to the three NS-NSAIDs (49-78 days). Patients were at the highest risk of switching within the first 100 days of therapy. After adjusting for potential confounding factors, the OR for switching to another NS-NSAID or COX-2 specific inhibitor ranged from 1.74 to 2.35 for the three NS-NSAIDs compared to celecoxib (all comparisons, p < 0.01). Similar findings were obtained when comparing rofecoxib to each of the three NS-NSAIDS (all comparisons, p < 0.01). When COX-2 inhibitors combined were compared to NS-NSAIDS combined, the OR for switching was 1.53 (95% confidence interval = 1.42-1.65; p < 0.01) after adjusting for potential confounders. CONCLUSIONS: Patients on the COX-2 specific inhibitors (celecoxib and rofecoxib) were significantly less likely to switch their therapy than patients on NS-NSAIDS (ibuprofen, naproxen and diclofenac). These results suggest that COX-2 specific inhibitors may be a more effective treatment option when compared with NS-NSAIDs in usual clinical practice. Copyright 2003 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15133778&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.

Zeytin HE, Patel AC, Rogers CJ, Canter D, Hursting SD, Schlom J, Greiner JW.

Laboratories of Tumor Immunology and Biology, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.

The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been well tolerated and capable of eliciting anti-CEA host immune responses in early clinical studies. The results suggest that the administration of a recombinant poxvirus-based vaccine is compatible with celecoxib, and this combined chemoimmuno-based approach might lead to an additive therapeutic antitumor benefit not only in patients diagnosed with familial adenomatous polyposis but, perhaps, in other preventive settings in which COX-2 overexpression is associated with progression from premalignancy to neoplasia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15150127&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs.

Peluffo GD, Stillitani I, Rodriguez VA, Diament MJ, Klein SM.

Departamento Bioterio y Cancer Experimental, Area Investigacion, Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires, Av. San Martin 5481, 1417 Buenos Aires, Argentina. bioterioroffo yehoo.com

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies. Copyright 2004 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15170663&dopt=Abstract celecoxib, Celebrex