Safety Of Celecoxib Research Articles

The efficacy of celecoxib in preventing heterotopic ossification recurrence after open arthrolysis for post-traumatic elbow stiffness in adults

Heterotopic ossification (HO) recurrence after joint surgery is always a disturbing problem for patients and surgeons. Our study was performed to assess the efficacy and safety of celecoxib in preventing the recurrence of HO after open arthrolysis for post-traumatic elbow stiffness. We retrospectively studied 152 patients with stiff elbows caused by post-traumatic HO. After surgery, 77 patients received celecoxib (200 mg once daily) for 28 days, whereas 75 did not. Radiographic evaluation was performed at 3, 6, and 9 months postoperatively. Univariate and multivariate analyses were performed to determine which factors affected HO recurrence. HO was both more common and more severe in the no-celecoxib group than in the celecoxib group at 3, 6, and 9 months after surgery. A significant difference was observed between the 2 groups in terms of postoperative extension (P = .030), flexion (P = .008), and pronation (P = .005); however, no significant difference in postoperative supination was noted (P = .622). Logistic regression analysis showed that taking celecoxib was the protective factor for HO recurrence, whereas overweight (body mass index > 25) and male gender were the risk factors. A short course of celecoxib aids in the prevention of HO recurrence after open arthrolysis for elbow stiffness in adults and could be an effective and safe option.

Celecoxib Versus Diclofenac in Mild to Moderate Depression Management Among Breast Cancer Patients: A Double-Blind, Placebo-Controlled, Randomized Trial.

Depression is a well-known complication of breast cancer, which is known to adversely affect quality of life, prognosis, and survival in breast cancer patients. Celecoxib, a nonsteroidal anti-inflammatory drug, which acts via the selective inhibition of cyclo-oxygenase (COX)-2, has been shown to have antidepressive effects. Here, we aimed to compare the efficacy and safety of celecoxib, a selective inhibitor of COX-2, with diclofenac, a nonselective inhibitor of both COX-1 and COX-2 in reducing depressive symptoms and pain in breast cancer patients. A total of 52 outpatients with breast cancer with mild to moderate depression, who suffered from pain and needed analgesics, participated in the trial and underwent 6 weeks of treatment with either celecoxib (200 mg twice daily) or diclofenac (50 mg twice daily). Participants were investigated using the Hamilton Depression Rating Scale (HDRS). The primary outcome measure was to compare the antidepressant effects of celecoxib and diclofenac. Repeated-measures analysis demonstrated significant effect for Time × Treatment interaction on the HDRS scores: F(1.76, 87.85) = 9.66; P < 0.001. By study conclusion, greater improvement was observed in the HDRS score of the celecoxib group compared with the diclofenac group (P = 0.002). No one experienced remission (HDRS ≤ 7) in either group. Frequencies of adverse events were not significantly different between groups. Celecoxib seems to possess superior antidepressive effects compared with diclofenac in breast cancer patients with mild to moderate depression.

Efficacy and safety of celecoxib compared with placebo and etodolac for acute postoperative pain: a multicenter, double-blind, randomized, parallel-group, controlled trial.

Celecoxib is a nonsteroidal anti-inflammatory drug (selective cyclooxygenase-2 inhibitor) that is widely used. The efficacy and safety of celecoxib for treatment of acute postoperative pain were evaluated in Japanese patients. The objective was to assess whether celecoxib showed superiority over placebo treatment and non-inferiority versus etodolac (another selective cyclooxygenase-2 inhibitor) that has been widely used for the management of acute pain. A multicenter, double-blind, randomized, parallel-group, controlled study was performed, in which 616 patients with postoperative pain received celecoxib, etodolac, or placebo. Their impressions of study drug efficacy (overall assessment) and pain intensity were evaluated. Based on each patient's overall assessment of pain, the efficacy rate was 63.7% in the placebo group, 76.2% in the celecoxib group, and 68.0% in the etodolac group, with these results demonstrating superiority of celecoxib to placebo and noninferiority versus etodolac. The efficacy rate was significantly higher in the celecoxib group than in the etodolac group. There were no adverse events specific to celecoxib, and the safety of celecoxib was similar to that of placebo. Celecoxib was superior to etodolac for controlling acute postoperative pain.

Efficacy and Safety of Celecoxib in Chinese Patients with Ankylosing Spondylitis: A 6-Week Randomized, Double-Blinded Study with 6-Week Open-Label Extension Treatment

BackgroundNonsteroidal anti-inflammatory drugs are the first-line option for treating ankylosing spondylitis (AS) in China. However, no large-scale controlled trials have been conducted in this ethnic population. ObjectiveTo evaluate the efficacy and safety of 6 weeks’ treatment with celecoxib in patients with AS in China. MethodsThis Phase 3, double-blind, parallel-group study randomized patients with AS aged ≥18 to 65 years 1:1 to receive celecoxib 200 mg once daily or diclofenac sustained release 75 mg once daily. After 6 weeks, patients could use celecoxib 400 mg once daily or maintain blinded therapy. The primary efficacy end point was mean change from baseline at Week 6 for Patient’s Global Assessment of Pain Intensity score (100-mm visual analog scale). Noninferiority was established if the upper bound of the CI was <10 mm. Secondary objectives included patients’ and physicians’ assessments of disease activity, change from baseline in C-reactive protein level, and safety. ResultsIn the per-protocol analysis set the least squares mean change from baseline in the Patient’s Global Assessment of Pain Intensity score at Week 6 was –23.8 mm and –27.1 mm in patients receiving celecoxib (n = 111) and diclofenac (n = 108), respectively. The 2-sided 95% CI for the treatment difference (celecoxib – diclofenac) was –2.2 to 8.8. Overall, 4.2% and 6.7% of patients in the celecoxib and diclofenac groups, respectively, reported treatment-related adverse events. All were mild to moderate in severity. ConclusionsCelecoxib 200 mg once daily is noninferior to diclofenac sustained release 75 mg once daily for pain treatment in Chinese patients with AS. ClinicalTrials.gov identifier: NCT00762463.

Efficacy and tolerability of celecoxib in osteoarthritis patients who previously failed naproxen and ibuprofen: results from two trials

Aims: To evaluate the efficacy and safety of celecoxib in patients with osteoarthritis who previously failed naproxen and ibuprofen treatment. Materials & methods: Two identical, 6-week, randomized, double-blind, placebo-controlled trials of celecoxib 200 mg daily were undertaken in patients with knee osteoarthritis. The primary efficacy variable was the 6-week change in Patient's Assessment of Arthritis Pain visual analog scale. Results: In study 1 (n = 370), the visual analog scale least squares mean decrease from baseline was 27.3 (celecoxib) versus 14.9 mm (placebo; p < 0.001); it was 28.0 versus 24.6 mm, respectively, in study 2 (n = 380). Conclusion: Celecoxib was well tolerated, yet the efficacy results differed, highlighting the complexities of treating patients with osteoarthritis who have failed previous NSAID treatment.

Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease.

Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease.

Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the Phase 4 registry.

BackgroundThis study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).MethodsChildren aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database.ResultsA total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use.ConclusionsThe safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive.Trial registrationClinicalTrials.gov identifier NCT00688545.

A prospective, randomized, double-blind, multicenter comparative study on the safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the treatment of osteoarthritis of knee joint

Ethnopharmacological relevanceThis prospective, randomized, double-blind, multicenter study compared the efficacy and safety of Celecoxib and GCSB-5, a new product from extracts of six herbs, for the treatment of knee osteoarthritis. Materials and methodsA total of 198 eligible patients were randomly assigned to the Celecoxib group (n=99 patients) or the GCSB-5 group (n=99 patients) for the 12-week study. The amount of change and percentage of the change in Western Ontario and McMaster Universities (WOMAC) Arthritis Index from the baseline, the change in pain on walking by visual analogue scale (VAS), physician's global assessment on response to therapy (PGART) by five point Likert scale, and the amount of rescue medicine taken were used as parameters for efficacy. Adverse drug reactions (ADRs) were carefully investigated. ResultsThe WOMAC score improved in both the Celecoxib group and GCSB-5 group by 20.5 and 21.3 (P=0.79). The percentage of the change in WOMAC score were −42.0% and −38.9% (P=0.54). The pain VAS score decreased by 29.9 and 27.9 (P=0.58). The responders by PGART were 95.3% and 93.8% (P= 0.66), and the median amount of rescue medicine taken were 2.0 and 6.5 tablets (P=0.06). The incidence of ADRs were 31.3% and 21.2% (P=0.11). The most common ADRs were gastrointestinal system related; 17.2% in GCSB-5 group and 22.2% in Celecoxib group. Any severe ADR was not observed in either group. ConclusionsThe result of this study supports that GCSB-5 is comparable to Celecoxib in terms of the efficacy and safety for the treatment of osteoarthritis of knee joint.

Reappraisal of the Therapeutic Role of Celecoxib in Cholangiocarcinoma

Cholangiocarcinoma (CCA), a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanced CCA. Cyclooxygenase-2 (COX-2) is a potential oncogene expressing in human CCA tissues and represents a candidate target for treatment; however, COX-2 inhibitors increase the risk of negative cardiovascular events as application for chemoprevention aim. Here, we re-evaluated the effectiveness and safety of celecoxib, one widely used COX-2 inhibitor, in treating CCA. We demonstrated that celecoxib exhibited an anti-proliferative effect on CGCCA cells via cell cycle arrest at G2 phase and apoptosis induction. Treatment for 5 weeks high dose celecoxib (160 mg/kg) significantly repressed thioacetamide-induced CCA tumour growth in rats as monitored by animal positron emission tomography through apoptosis induction. No obviously observable side effects were noted during the therapeutic period. As retrospectively reviewing 78 intrahepatic mass-forming CCA patients, their survival was strongly and negatively associated with a positive resection margin and high COX-2 expression. Based on our result, we concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA. Yet its clinical application still needs more studies to prove its safety.

Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials

Objective: Further understand the safety profile of celecoxib and provide safety information for important adverse events (AEs).Methods: Analysis of randomized controlled trials from the Pfizer clinical trial repository (final study reports completed by 31 July 2011) in which celecoxib was compared with placebo or non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) for treatment of pain or inflammation in adults. Safety end points comprised 18 terms that had been identified as important AEs among all NSAIDs.Results: There was a greater risk of edema (risk difference (95% confidence interval) 0.77% (0.45, 1.09)); hypertension (0.28% (-0.01, 0.57)); angioedema (0.16% (-0.06, 0.39) and allergic reactions (0.15% (-0.10, 0.40)) with celecoxib than with placebo, while a greater risk of gastrointestinal (GI) hemorrhage (-0.15% (-0.47, 0.16)) was seen with placebo. There was a greater risk of GI hemorrhage (-0.53% (-0.72, -0.33)), GI ulceration (-0.46% (-0.60, -0.33)), edema (-0.62% (-0.89, -0.35)) and hypertension (-0.57% (-0.82, -0.33)) with nsNSAIDs than with celecoxib.Conclusions: The magnitude of risks associated with NSAIDs is small and similar in celecoxib-, nsNSAID- and placebo-treated patients. This analysis provides safety information that will allow physicians to make informed treatment decisions for patients who are appropriate candidates for celecoxib use.

Response to Nonsteroidal Anti-inflammatory Drugs in African Americans with Osteoarthritis of the Knee

This 6-week, randomized, double-blind, parallel-group study compared the analgesic efficacy, tolerability and safety of celecoxib, naproxen and placebo in African Americans with osteoarthritis (OA) of the knee. A total of 322 patients aged ≥ 45 years with OA of the knee in a flare state received 200 mg celecoxib orally once daily, 500 mg naproxen orally twice daily or placebo for 6 weeks. The primary endpoint was change from baseline in the Patient's Assessment of Arthritis Pain. Celecoxib was as effective as naproxen in reducing OA pain. Similar efficacy was observed in many of the secondary outcome measures. Celecoxib was well tolerated and demonstrated favorable upper gastro-intestinal tolerability. Improvements in outcome measures were numerically greater in the active treatment groups compared with the placebo group, but did not reach statistical significance. Celecoxib was as effective as naproxen in relieving OA pain in African Americans and was well tolerated. Few significant differences were observed between active treatments and placebo, possibly because of a strong placebo effect.

Efficacy and safety of celecoxib versus diclofenac and omeprazole in elderly arthritis patients: a subgroup analysis of the CONDOR trial

Objective:To compare the safety and efficacy of celecoxib versus diclofenac slow release (SR) plus omeprazole in elderly arthritis patients.Research design and methods:Patients aged ≥65 years, with osteoarthritis and/or rheumatoid arthritis, at high gastrointestinal (GI) risk who participated in the CONDOR trial (Celecoxib vs. Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) were included in this subanalysis. CONDOR was a 6-month prospective, double-blind, randomized, parallel-group, multicenter, international study comparing treatment with celecoxib 200 mg twice daily (BID) versus diclofenac SR 75 mg BID plus omeprazole 20 mg daily.Main outcome measures:The primary end point was a composite of Clinically Significant Upper and Lower GI Events adjudicated by an independent blinded expert committee. Efficacy was determined by the Patient’s Global Assessment of Arthritis.Results:A total of 2446 patients aged ≥65 years were included in the intent-to-treat (ITT) population (n = 1219 celecoxib; n = 1227 diclofenac). Eight patients in the celecoxib group and 52 in the diclofenac group were adjudicated as having Clinically Significant Upper and Lower GI events (adjusted odds ratio: 6.27; p < 0.0001). Clinically significant reductions in hemoglobin (≥2 g/dL) and/or hematocrit (≥10%) were observed in 23 patients in the celecoxib group and in 76 in the diclofenac group (relative risk: 3.22 [95% confidence interval: 2.04–5.07]; p < 0.0001). Incidence of moderate-to-severe abdominal symptoms and discontinuation of treatment due to GI adverse events (AEs) were lower in the celecoxib group. The Patient’s Global Assessment of Arthritis score least squares mean change from baseline to final visit and percentage of patients rating treatment efficacy as good/very good at baseline and final visit were similar in both groups.Limitations:The dose of celecoxib used is consistent with the European label for the management of osteoarthritis and may not reflect what is commonly prescribed in current clinical practice in the United States. The data were obtained in a clinical trial setting where patients were enrolled based on specific inclusion and exclusion criteria; as such, the patients may not be broadly representative of the patient population in a general practice setting.Conclusions:Efficacy was comparable in the two treatment groups. There were fewer endpoints as well as fewer GI AEs reported in patients treated with celecoxib compared with diclofenac. These data may help physicians in their treatment decisions for elderly patients with arthritis.

Preparation of celecoxib solid dispersions for dermal application: in vitro characterization and skin irritation test

The purpose of this work was to improve the dissolution and skin permeability characterestics of celecoxib. Solid dispersions (SDs) of celecoxib were prepared using PEG 4000, PVP K30 and HPβCD by the kneading method. The dispersions were characterized by, (DSC), (XRD) and in vitro drug dissolution. The solubility and dissolution of SDs were markedly increased as compared to plain drug. The kneaded dispersions showing high dissolution were incorporated in an o/w cream and evaluated for in vitro drug permeation through rabbit skin. The permeation rate of celecoxib were significantly increased in the case of SDs when compared to plain drug. The anti-inflammatory effect of celecoxib-PVP K30 cream was more effective in inhibiting rat paw edema when compared to celecoxib cream. Skin irritancy and histopathological investigation of rat skin revealed its safety thus confirming the advantage of improved pharmacological activity and safety of celecoxib when administered topically as solid dispersion with PVPK30.

Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs).MethodsA double-blind placebo-controlled randomized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests. All statistical tests were two-sided.ResultsThere was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma skin cancer history, and patient time on study, the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm (RR = 0.41, 95% CI = 0.23 to 0.72, P = .002) as were the numbers of BCCs (RR = 0.40, 95% CI = 0.18 to 0.93, P = .032) and SCCs (RR = 0.42, 95% CI = 0.19 to 0.93, P = .032). Serious and cardiovascular adverse events were similar in the two groups.ConclusionsCelecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers.

Strategies for making analgesia safer: The role of comparative effectiveness research

Strategies for making analgesia safer: The role of comparative effectiveness research

Abstract 3724: Efficacy and safety of the COX-2 inhibitor celecoxib on patients with cancer cachexia: a phase II non randomized study

Abstract Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase (COX)-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome. We carried out a prospective non randomised phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib (300 mg/day for 4 months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. Patient eligibility criteria were: age range of 18-80 years, histologically confirmed tumor of any site at an advanced stage, loss of ≥5% of body weight in the previous 3 months and a life expectancy of ≥4 months. Patients could be receiving concomitant antineoplastic chemotherapy or hormone therapy with palliative intent or supportive care. Exclusion criteria were: women of child-bearing age, positive history of heart disease, history of previous myocardial infarction, unstable angina, coronary revascularization, uncontrolled arrhythmia, congestive heart failure and cerebrovascular accident, previous gastrointestinal inflammatory disease and history of gastrointestinal ulceration, mechanical obstruction to feeding, and medical treatments inducing significant changes of patient metabolism or body weight. A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable. The men/women ratio was well balanced (13/11). The mean age was 60.6 years. The most frequent tumor sites were head and neck, lung, and colorectal. Patients were &amp;gt;90% stage IV and the Glasgow Prognostic Score (GPS), an inflammation-based score predictive of patient survival, was high (two) in 50% of them. Among primary efficacy endpoints, LBM assessed both by BIA (mean increase, +0.6±2.4 kg) and DEXA (mean increase, +0.6±2.7 kg) increased significantly (p&amp;lt;0.0001). The proinflammatory cytokine TNF-α decreased significantly (mean decrease, —6.9±11 pg/ml; p=0.007). Among patients with weight loss associated with high TNF-α levels (16), ten showed an increase of LBM accompanied by a decrease of TNF-α levels, while two showed an increase of LBM without a concomitant decrease of TNF-α. Among secondary efficacy endpoints, an improvement of grip strength, quality of life, performance status, and Glasgow prognostic score was shown. There were no grade 3/4 toxicities. Patient compliance was very good; no patient had to reduce the celecoxib dosage nor interrupt treatment. Our results show that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia. Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3724.

Efficacy and Safety of Celecoxib in the Treatment of Acute Pain due to Ankle Sprain in a Latin American and Middle Eastern Population

Ankle sprains are common acute soft-tissue injuries. This 7-day open-label, multicentre, randomized study compared the efficacy and safety of celecoxib with non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in treating acute ankle sprain with moderate-to-severe ankle pain in 278 patients. Patients received either celecoxib (400 mg loading dose followed by 200 mg twice daily) or standard doses of non-selective NSAIDs. The primary endpoint was a change in the patient's assessment of ankle pain on a 0 mm (no pain) - 100 mm (worst possible pain) visual analogue scale (VAS) at day 3 compared with baseline. From a baseline of 73 mm, mean VAS pain scores decreased to 29 and 32 mm in the celecoxib and non-selective NSAID groups, respectively. The lower limit of the 95% confidence interval for the treatment difference with regard to change from baseline was greater than the pre-established non-inferiority margin of -10 mm. Using an initial loading dose, celecoxib was at least as efficacious as non-selective NSAIDs in treating acute pain due to ankle sprain.

Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia

Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome. We carried out a prospective phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib (300 mg/day for 4 months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable. A significant increase of lean body mass and a significant decrease of TNF-alpha were observed. Moreover, an improvement of grip strength, quality of life, performance status, and Glasgow prognostic score was shown. There were no grade 3/4 toxicities. Patient compliance was very good; no patient had to reduce the celecoxib dosage nor interrupt treatment. Our results showed that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia. Although the treatment of cancer cachexia, a multifactorial syndrome, is more likely to yield success with a multitargeted approach; in the present study, we were able to show that a treatment, such as celecoxib, addressing a single target, albeit very important as chronic inflammation, could have positive effects. Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib.

A phase II clinical trial of celecoxib combined with platinum-based regimen as first-line chemotherapy for advanced non-small cell lung cancer patients with cyclooxygenase-2 positive expression

To evaluate the efficacy and safety of celecoxib plus platinum-doublet as first-line chemotherapy in treatment of advanced non-small cell lung cancer (NSCLC), and to determine the subgroup benefiting from celecoxib combined therapy by molecular analysis. A total of 44 treatment-naive patients of advanced NSCLC with positive cyclooxygenase-2 (COX-2) expression confirmed by immunohistochemical (IHC) staining were designed to receive celecoxib plus platinum-doublet chemotherapy (cisplatin plus gemcitabine, novelbine or docetaxol) from February 2005 to May 2007. On 5–7 day before chemotherapy, 400 mg celecoxib was administered twice a day orally until obvious evidence of disease progression or intolerable toxicity was found. Adverse events were recorded according to NCI-CTC criteria. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), 1-year survival rate, response rate (RR) and safety. Additionally, we detected epithelial growth factor receptor (EGFR) status including EGFR gene amplification by real-time PCR and gene mutations by DHPLC followed by sequencing. The response rate was 45% (20/44), and the disease control rate (DCR) was 59% (26/44). The median progression-free survival time and median survival time were 6 m and 18 m, respectively. The 1-year survival rate was 68%. Chemotherapy cycle numbers and best response were found to be the predictive factors for PFS by COX model analysis (P=0.023 and P=0.000, respectively). No factor was found to affect OS. The most common toxicities included neutropenia and nausea/vomit. EGFR gene amplification was an independent prognostic factor influencing OS (P=0.0002). Patients with EGFR mutations (exon 21) had a tendency of disease progression (P=0.041). Encouraging activities of celecoxib combined with platinum-doublet chemotherapy were demonstrated in treatment-naive patients with advanced NSCLC, with good tolerances. For COX-2 IHC positive patients, positive EGFR amplification and mutation might be related to poor clinical outcomes.

A Prospective Study Comparing Celecoxib with Naproxen in Children with Juvenile Rheumatoid Arthritis

To compare the efficacy and safety of celecoxib and naproxen in children with juvenile rheumatoid arthritis (JRA). In this multicenter, randomized, double-blind, noninferiority study, subjects with JRA were randomized to receive a target dose of celecoxib 3 mg/kg bid or 6 mg/kg bid, or a target dose of naproxen 7.5 mg/kg bid for 12 weeks (maximum allowed dose=600 mg total daily dose). The primary efficacy measure was the percentage of responders at Week 12 attaining the American College of Rheumatology pediatric 30% improvement criterion (ACR Pediatric-30). Both celecoxib doses were at least as effective as naproxen at Week 12 [ACR Pediatric-30 treatment differences: celecoxib 3 mg/kg bid-naproxen=1.36% (95% CI -13.08 to 15.80); celecoxib 6 mg/kg bid-naproxen=13.02% (95% CI -0.22 to 26.25)]. Celecoxib 6 mg/kg bid had a numerically higher response rate than celecoxib 3 mg/kg bid at all postrandomization visits and a numerically higher response rate than naproxen 7.5 mg/kg bid at Weeks 4, 8, and 12. Improvement in each ACR Pediatric-30 core set measure was comparable to or numerically higher for celecoxib 6 mg/kg bid than naproxen or celecoxib 3 mg/kg bid. Adverse event rates were similar for all treatment groups, except that gastrointestinal adverse events were more common in the naproxen group, although the difference was not statistically significant. Celecoxib 3 mg/kg bid and 6 mg/kg bid were at least as effective as naproxen 7.5 mg/kg bid in treating the signs and symptoms of JRA over 12 weeks. All treatments were generally well tolerated.