Efficacy Of Selective COX-2 Inhibitors Research Articles

Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

BackgroundThe efficacy of selective cox-2 inhibitors in postoperative pain reduction were usually compared with conventional non-selective conventional NSAIDs or other types of medicine. Previous studies also used selective cox-2 inhibitors as single postoperative dose, in continued mode, or in combination with other modalities. The purpose of this study was to compare analgesic efficacy of single preoperative administration of etoricoxib versus celecoxib for post-operative pain relief after arthroscopic anterior cruciate ligament reconstruction.MethodsOne hundred and two patients diagnosed as anterior cruciate ligament injury were randomized into 3 groups using opaque envelope. Both patients and surgeon were blinded to the allocation. All of the patients were operated by one orthopaedic surgeon under regional anesthesia. Each group was given either etoricoxib 120 mg., celecoxib 400 mg., or placebo 1 hour prior to operative incision. Post-operative pain intensity, time to first dose of analgesic requirement and numbers of analgesic used for pain control and adverse events were recorded periodically to 48 hours after surgery. We analyzed the data according to intention to treat principle.ResultsAmong 102 patients, 35 were in etoricoxib, 35 in celecoxib and 32 in placebo group. The mean age of the patients was 30 years and most of the injury came from sports injury. There were no significant differences in all demographic characteristics among groups. The etoricoxib group had significantly less pain intensity than the other two groups at recovery room and up to 8 hours period but no significance difference in all other evaluation point, while celecoxib showed no significantly difference from placebo at any time points. The time to first dose of analgesic medication, amount of analgesic used, patient's satisfaction with pain control and incidence of adverse events were also no significantly difference among three groups.ConclusionsEtoricoxib is more effective than celecoxib and placebo for using as preemptive analgesia for acute postoperative pain control in patients underwent arthroscopic anterior cruciate ligament reconstruction.Trial registration numberNCT01017380

Cyclooxygenase-2 (COX-2): a molecular target in prostate cancer

Epidemiological studies provided the first evidence that COX may be involved in the pathogenesis of cancer. In the process of carcinogenesis and in the route of intracellular signalling during carcinogenesis, COX-2 expression may be a universal phenomenon. In general, COX-2 is up-regulated throughout the tumorigenic process, from early hyperplasia to metastatic disease. COX-2 has been reported to be constitutively overexpressed in a variety of malignancies and is frequently constitutively elevated in prostate carcinoma. COX-2 was consistently overexpressed in premalignant lesions such as prostatic intraepithelial neoplasia, and carcinoma. Cases are described with evolution of proliferative inflammatory atrophy of the prostate and prostate carcinoma. The increase of evidence implicating COX-2 in cancer has stimulated clinical trials to investigate the efficacy of selective COX-2 inhibitors in individuals at risk for human cancer. Regarding prostate carcinoma there is much direct or indirect evidence to support the use of COX-2 inhibitors in this disease. Trials using these drugs in familial adenomatous polyposis (FAP) and other patients with a high risk of colorectal carcinoma are ongoing.

Non-steroidal anti-inflammatory drugs in the treatment of genitourinary malignancies: focus on clinical data

The antitumour activity of NSAIDs in preclinical trials has lead to their evaluation in the management of various malignancies in humans. Evidence regarding their use in the treatment of genitourinary tumours is reviewed here, focusing primarily on clinical data. The majority of available evidence comes from meeting abstracts and only a few published manuscripts were detected. The efficacy of selective COX-2 inhibitors, a subcategory of anti-inflammatory drugs, is promising in prostate cancer, in either biochemical recurrence after initial treatment or advanced disease. This does not seem to be the case for renal tumours in which efficacy in the advanced disease setting is not satisfactory. Despite the well-documented rationale for the application of NSAIDs in bladder cancer management, clinical evidence is not available. More studies are needed to assess the efficacy of anti-inflammatory agents in bladder cancer treatment and further clarify their therapeutic benefit in patients with prostate cancer, in which initial results are encouraging.

Comparing Valdecoxib, Hydrocodone/acetaminophen, And Placebo In Relieving Golf-related Osteoarthritic Back Pain And Improving Swing Performance

Introduction Data supports the efficacy of selective COX-2 inhibitors in chronic treatment of osteoarthritis (OA). However, the efficacy of a single dose for the acute or pre-emptive relief of back pain and restoration of function during the high demand sport of golf has not been documented. Purpose To provide data on the efficacy of the COX-2 inhibitor valdecoxib 10 mg (BextraTM) compared to hydrocodone/acetaminophen 5/500 mg (VicodinTM) and placebo in reducing or relieving acute back pain induced by the golf swing in patients with OA of the lumbar spine. This study also examined the effects of these agents on golf swing performance. Methods This randomized, double-blind, cross-over, 12 week study compared the effects of a single dose of valdecoxib (10 mg), hydrocodone/acetaminophen (5/500 mg), and placebo, on an initial baseline measurement of subjective pain (SF-36, Oswestry) and the biomechanical assessment of the golf swing as measured during simulated golf play. A drug wash-out period of ≥7–10 days was utilized between each treatment arm. Golf swing performance was measured via Motion Analysis (240 Hz, 37 markers, 15 segment body) with emphasis on hip and shoulder trunk rotations and peak club head velocity. Data between treatement arms were compared with a RMANOVA (p≤.05) with a Bonferroni adjustment for post-hocs. Results Valdecoxib and hydrocodone/acetaminophen were clinically equal to each other and statistically superior to placebo and baseline measures in improving baseline SF-36 and Oswestry scores. These drugs also promoted greater hip (p≤.05) and shoulder rotations (p≤.05) and increased club head speed (p≤.05) compared to placebo and baseline measures. Conclusion In senior golfers with low back OA, a pre-emptive dose of valdecoxib (10 mg) is as effective as the opioid analgesic, hydrocodone/acetaminophen (5/500 mg), in alleviating golf-induced low back pain and improving golf swing performance as measured by greater hip and shoulder rotations as well as club head speed.

Variability of pro-apoptotic properties of cyclooxygenase-2 inhibitors in rheumatoid synovial fibroblasts and cancer cell lines

Recent attention has been focused on selective cyclooxygenase (COX)-2 inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-2 without inhibition of COX-1, resulting in fewer incidences of adverse reactions. Various clinical studies have confirmed that the efficacy of selective COX-2 inhibitors for the patients with rheumatoid arthritis (RA) is similar to that of conventional NSAIDs; however, they cause fewer severe gastrointestinal complications. Recently, we found that some conventional NSAIDs such as indometacin and diclofenac induced apoptosis in association with activation of peroxisome proliferator-activated receptor gamma (PPARγ) in rheumatoid synovial fibroblasts (RSF). We also found that celecoxib, a selective COX-2 inhibitor, specifically induced apoptosis and inhibited proliferation of RSF in COX-2-independent and PPARγ-independent manners. Other selective COX-2 inhibitors such as etodolac, meloxicam, nimesulide, NS-398, and rofecoxib, even in very high concentrations, did not induce apoptosis in RSF at all. These results suggested that some NSAIDs including a selective COX-2 inhibitor might be used as disease-modifying antirheumatic drugs if they could be delivered with good efficiency to the affected synovia of patients with RA. It is well known that administration of celecoxib decreases the number of colon polyps in patients with familiar adenomatous polyposis. The pro-apoptotic effect of celecoxib was also observed in several kinds of cell lines derived from colon cancer and ovarian cancer, suggesting a common mechanism of action of celecoxib-induced apotosis among RSF and cancer cell lines. Inactivation of Akt might explain the pro-apoptotic effect of celecoxib on at least colon cancer cell lines.

A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors.

In this study, PGE2 levels in lipopolysaccharide (LPS)-challenged human whole blood and TxB2 levels following blood coagulation were measured as biochemical index for cyclooxygenase (Cox)-2 and Cox-1 activity respectively. Incubation of human mononuclear cells isolated from whole blood with LPS (100 mu g/mL) induced a time-dependent increase in the expression of Cox-2 protein (>100 fold at 24 hr). This is associated with increases in PGE2 production and free arachidonate release in the plasma. Cox-1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS. Most non-steroidal anti-inflammatory drugs (NSAIDs) are more potent at inhibiting Cox-1 than Cox-2. Five experimental compounds CGP-28238, Dup-697, NS-398, SC-58125 and L-745,337, have a greater selectivity for Cox-2. Indomethacin at a single oral dose (25 mg) inhibited approximately 90% the whole blood Cox-2 and Cox-1 activities ex vivo in healthy subjects. These results support the use of this assay to assess the biochemical efficacy of selective Cox-2 inhibitors in clinical trials.