Trial Of Celecoxib Research Articles

A phase II trial of celecoxib in addition to neoadjuvant concurrent chemoradiation for patients diagnosed with locally advanced rectal adenocarcinoma.

A phase II trial of celecoxib in addition to neoadjuvant concurrent chemoradiation for patients diagnosed with locally advanced rectal adenocarcinoma.

A Phase II Trial of Celecoxib with Neoadjuvant Concurrent Chemoradiation for Patients with Localized Rectal Adenocarcinoma Stage II and III

Abstract Background In recent years, neoadjuvant chemoradiation and subsequent surgical resection with total mesorectal excision has been shown to increase local control with decreased toxicity in comparison to upfront surgical resection followed by adjuvant chemoradiation. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluated the efficacy of adding a selective COX-2 inhibitor to standart neoadjuvant chemoradiation on pathologic response, sphincter preservation and acute toxicity. Materials and Methods Thirty patients with Adenocarcinoma of rectum (up to 15 cm of anal verge) were enrolled in this phase 2 study. Patients undergone full colonoscopy, MRI rectal protocol, abdomino-pelvic and chest CT scan for staging then received neoadjuvant concurrent chemoradiation (capecitabine 825 mg/m2 bid in combination with celecoxib 200 mg bid and radiotherapy (50-50.4Gy/25-28fraction). Surgery was done 5-12 weeks after chemoradiation. Acute complications were scored by common toxicity criteria 5.0 and tumor response was graded according to AJCC and CAP guidelines for rectal adenocarcinoma. Results Of 30 patients, total mesorectal excision was done in 22 patients. Tumor regression grade was reported as: 7 patients (31.8%) had grade 0 or complete response, 7 patients (31.8%) had grade 1 or moderate response, 6 patients (27%) had grade 2 or minimal response and 2 patients (9%) had grade 3 or poor response. Primary tumor down staging was 63% and nodal down staging was 73% with sphincteric preservation rate of 77% among the operated cohort. No patients had hematologic or cardio-vascular toxicity. Conclusion Results indicate celecoxib in combination with neoadjuvant chemoradiation is safe and associated with low toxicity. This combination can promote pathologic complete response, tumor regression grade, sphincteric preservation, T and N down staging in rectal adenocarcinoma.

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis.

To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer

Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking. To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer. The Randomized European Celecoxib Trial (REACT) was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany testing 2 years of adjuvant celecoxib vs placebo among 2639 patients recruited between January 19, 2007, and November 1, 2012, with follow-up 10 years after treatment completion. Eligible patients had completely resected breast cancer with local and systemic therapy according to local practice. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. Randomization was in a 2:1 ratio between celecoxib or placebo. Statistical analysis was performed from May 5, 2019, to March 5, 2020. Patients received celecoxib, 400 mg, or placebo once daily for 2 years. The primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population using Cox proportional hazards regression and log-rank analysis. Follow-up is complete. A total of 2639 patients (median age, 55.2 years [range, 26.8-86.0 years]) were recruited; 1763 received celecoxib, and 876 received placebo. Most patients' tumors (1930 [73%]) were estrogen receptor positive or progesterone receptor positive and ERBB2 negative. A total of 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors. At a median follow-up of 74.3 months (interquartile range, 61.4-93.6 years), DFS events had been reported for 487 patients (19%): 18% for those who received celecoxib (n = 323; 5-year DFS rate = 84%) vs 19% for those who received placebo (n = 164; 5-year DFS rate = 83%); the unadjusted hazard ratio was 0.97 (95% CI, 0.80-1.17; log-rank P = .75). Rates of toxic effects were low across both treatment groups, with no evidence of a difference. In this randomized clinical trial, patients showed no evidence of a DFS benefit for 2 years' treatment with celecoxib compared with placebo as adjuvant treatment of ERBB2-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS benefit, but further studies would be required to test this possibility. ClinicalTrials.gov Identifier: NCT02429427 and isrctn.org Identifier: ISRCTN48254013.

Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent

Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. A total of 428 participants aged 40-80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P=4.41×10-7), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P=0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P=8.67×10-8). This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

Microglial Activation and Response to Anti-inflammatory Treatment in Major Depressive Disorder: Another Piece in the Inflammation–Mood Disorders Puzzle

There is good news and bad news when it comes to our understanding of inflammation in the pathogenesis and treatment of major depressive disorder (MDD). The bad news is that, like the dexamethasone suppression test or the efficacy of antidepressants before it, inflammation is oversold as an answer to the mystery of depression and its treatment. The good news is that an unusually replicable set of findings (for psychiatry) increasingly paints a consistent picture of the ways in which inflammation is of value in understanding MDD. In the current issue of Biological Psychiatry, Attwells et al. ( 1 Attwells S. Setiawan E. Rusjan P.M. Xu C. Hutton C. Rafiei D. et al. Translocator protein distribution volume predicts reduction of symptoms during open-label trial of celecoxib in major depressive disorder. Biol Psychiatry. 2020; 88: 649-656 Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar ) simultaneously extend and confirm what we know already about how brain and body work together when it comes to inflammation and its role in MDD. SEE CORRESPONDING ARTICLE ON PAGE 649 SEE CORRESPONDING ARTICLE ON PAGE 649 Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive DisorderBiological PsychiatryVol. 88Issue 8PreviewGliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder. Full-Text PDF

First person profile: Monica Bertagnolli, MD: An international oncology leader and noted surgical oncologist, Dr. Monica Bertagnolli has forged her own path.

First person profile: Monica Bertagnolli, MD: An international oncology leader and noted surgical oncologist, Dr. Monica Bertagnolli has forged her own path.

The cardiovascular risk of celecoxib for knee osteoarthritis: A protocol for systematic review and meta-analysis.

The aim of this systematic review and meta-analysis is to assess the cardiovascular (CV) risk of celecoxib on knee osteoarthritis (KOA) patients compared with the risk in those prescribed other non-selective non-steroidal anti-inflammatory drugs (NSAIDs), no intervention or placebo-controlled patients. The following databases will be searched: MEDLINE, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese Nation Knowledge Infrastructure, Wanfang Database, and the Chongqing VIP from inception to April 1, 2020. All randomized controlled trials (RCTs) of celecoxib that presented data on serious cardiovascular events among KOA patients will be included. Study selection, data extraction, quality assessment, and assessment of risk bias will be performed by 2 reviewers independently. Odds ratios and correlative 95% confidence intervals will be calculated to present the association between the celecoxib and CV risk using Review Manager version 5.3 when there is sufficient available data. This review does not require ethical approval. The results of this review may be published in a peer-reviewed journal or disseminated at relevant conferences. CRD42020166721.

Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive Disorder

BackgroundGliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder. MethodsA total of 41 subjects with treatment-resistant major depressive disorder underwent one [18F]FEPPA positron emission tomography scan to measure PFC and ACC TSPO VT. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS). ResultsCumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted against PFC and ACC TSPO VT, showing a significant nonlinear relationship. At low TSPO VT values, there was no reduction in HDRS scores, but as TSPO VT values increased, there was a reduction in HDRS scores that then plateaued. This was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO VT accounted for 84% and 92% of the variance, respectively. ConclusionsCelecoxib administration in the presence of gliosis labeled by TSPO VT is associated with greater reduction of symptoms. Given the predictiveness of TSPO VT on symptom reduction, this personalized medicine approach of matching a marker of gliosis to medication targeting effects of gliosis should be applied in early development of novel therapeutics, in particular for treatment-resistant major depressive disorder.

Role of Anti-inflammatory Drugs in the Colorectal Cancer.

Objective: The objective of this review was to systematically review and synthesize evidence regarding benefits of using nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of colorectal cancer (CRC). Data Sources: The data sources were MEDLINE, PubMed, NEJM, Google Scholar, and Google searches of references from relevant and eligible trials. Review Methods: We screened abstracts and full-text articles of identified references for eligibility and reviewed randomized controlled trials, cohort studies, and meta-analysis for evidence on benefits of using NSAIDs in CRC treatments. For all extracted data, completeness and relevance were checked. Results: The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence interval [CI] = 0.39-0.98; P trend with NSAID use frequency = .03). Long-term use of aspirin reduces the risk of CRC. Aspirin also reduces the incidence of colon adenomas and mortality, especially when used for >10 years. Rofecoxib is associated with the reduction of CRC; however, it was associated with cardiovascular risk (with an overall unadjusted relative risk of 1.50 [95% CI = 0.76-2.94; P = .24]). Adenoma Prevention with Celecoxib trial shows that, for patients of all genotypes, the estimated cumulative incidence of one or more adenomas by year 3 was 59.8% for those randomized to placebo as compared with 43.3% for those randomized to low-dose (200 mg, twice daily) celecoxib (relative risk [RR] = 0.68; 95% CI = 0.59-0.79; P < .001) and 36.8% for those randomized to high-dose (400 mg, twice daily) celecoxib and 60.7% in placebo group (RR = 0.54; 95% CI = 0.46-0.64; P < .001). Conclusions: The use of COX-2 inhibitors both prior to and after diagnosis of CRC seemed to be mildly associated with the reduction in mortality of patients with CRC. Some literatures state that COX-2 inhibitors might play a synergistic role in adjuvant chemotherapy of FOLFOX regimen. Celecoxib was found to increase the radiosensitization of colon cancer cells.

Randomized Double-blind Placebo-controlled Trial of Celecoxib for the Prevention of Skin Toxicity in Patients Receiving Radiation Therapy for Breast Cancer.

The skin toxicity-induced by ionizing radiation may limit the duration of treatment and may lead to discomfort in quality of life of patients during radiotherapy. The purpose of this randomized, placebo-controlled, double-blind study was to investigate the preventive effect of oral administration of celecoxib (CLX) on the acute radiation- induced skin toxicity in patients with breast cancer. Sixty breast cancer patients were randomly assigned to use CLX (400 mg per day) or placebo capsules during radiotherapy. Radiation-induced dermatitis was classified according to the radiation therapy oncology group (RTOG) criteria, as well as pain and itching were scored according to the VAS (Visual Analogue Scale) for six weeks of treatment. Breast swelling was evaluated through increase in the size of the breast during radiotherapy. Oral administration of CLX capsule during and after radiotherapy reduced significantly radiation-induced itching and pain in patients with breast cancer. CLX reduced the frequency of increased breast size caused by radiotherapy in patients as compared with placebo; however, this difference was statistically not significant. Patients who received CLX had insignificantly skin dermatitis when compared with placebo group. However, CLX was unable to reduce the dermatitis caused by ionizing radiation; it significantly reduced itching and pain in patients during radiotherapy. CLX may have beneficial effects in the quality life of breast cancer patients for treatment.

Abstract GS3-03: A phase III multicentre double blind randomised trial of celecoxib versus placebo in primary breast cancer patients (REACT – Randomised EuropeAn celecoxib trial)

Abstract Background Inhibition of COX-2 has been shown to attenuate the metastatic process in pre-clinical models of human breast cancer (BC). The primary aim of this study was to assess the effect of 2 years adjuvant therapy with the COX-2 inhibitor celecoxib compared with placebo in HER2-ve primary BC patients. Patients &amp; Methods Patients were randomised in a 2:1 ratio to receive celecoxib 400mg once daily or placebo for 2 years. Patients had to have completely resected BC with prior local and systemic adjuvant treatment according to local practice. Concurrent radiotherapy was permitted and hormone receptor +ve patients received endocrine therapy according to local practice. Patients with HER2+ or node negative, T1 and grade 1 disease were excluded. Median age of patients was 55 years (IQR: 49-63). 50% of patients had tumours &amp;gt;2cm; 42% were grade 3; 48% had node +ve disease. According to local assessment 73% were ER/PgR +ve. Primary endpoint was Disease Free Survival (DFS); defined as time from randomisation to date of first event, with events contributing to analysis defined as recurrence (distant/local), new primary BC (ipsilateral/contralateral) and death. Secondary endpoints included Overall Survival (OS), toxicity, cardiovascular mortality and incidence of second primaries. Subgroup analysis by hormone receptor status was pre-planned. Survival endpoints are analysed using Cox-proportional hazards and log-rank tests; restricted mean survival is used where proportional hazards do not hold. Results Between January 2007 and November 2012, 2639 patients were randomised (1763 celecoxib; 876 placebo) from 181 centres across the UK and Germany. At 13th April 2017, median follow up was 60 months (IQR: 48-72) with 428 DFS events reported. Unadjusted survival analysis results are presented below, with hazard ratio&amp;lt;1 favouring celecoxib: 5 year survival estimate (95% CI)Hazard ratio (95% CI)p-valueDFS (all patients) Celecoxib83% (81, 85)1.02 (0.83 – 1.24)0.88Placebo83% (80, 86)1- DFS within ER+ Celecoxib87% (85, 89)0.89 (0.69 – 1.16)0.40Placebo86% (83, 89)1- DFS within ER- Celecoxib72% (68, 76)1.17 (0.85 – 1.61)0.33Placebo75% (69, 80)1- OS (all patients) Celecoxib90% (88, 91)0.97 (0.75 – 1.25)0.81Placebo90% (88, 92)1- The interaction between ER status and treatment was not significant; p=0.36. In the celecoxib and placebo groups there were 17 and 8 deaths respectively in patients who had not relapsed. These were due to cardiac (n=3; 2) and other (n=14; 6) in the celecoxib and placebo groups respectively; none were GI related. In total 304 serious adverse events were observed in 265 patients (186/1763 celecoxib; 79/876 placebo). In the celecoxib and placebo groups respectively these were related to cardiac (n=12; 7), GI (n=9; 2) and other (n=193; 81). Work is ongoing to determine whether a subset of ER+ patients whose primary tumours show the characteristics of a COX-2 signature receive greater benefit from celecoxib. Conclusions There is no benefit of celecoxib in the ITT population. Further exploratory studies focussing on the ER+ subpopulation are ongoing. Celecoxib treatment is not associated with significant toxicity when compared to placebo in this population of BC patients. Citation Format: Coombes RC, Tovey H, Kilburn L, Mansi J, Palmieri C, Bartlett J, Hicks J, Makris A, Evans A, Loibl S, Denkert C, Murray E, Grieve R, Coleman R, Schmidt M, Klare P, Rezai M, Rautenberg B, Klutinus N, Rhein U, Mousa K, Ricardo-Vitorino S, von Minckwitz G, Bliss J. A phase III multicentre double blind randomised trial of celecoxib versus placebo in primary breast cancer patients (REACT – Randomised EuropeAn celecoxib trial) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-03.

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2), followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2), and etoricoxib, which ranged from 0.005 to 0.930 (×10−2). Conclusion Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

Clinical trial of celecoxib for recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP), caused by HPV 6/11, is managed by surgery but papilloma frequently recur. COX-2 and its product PGE2 are overexpressed in RRP. Celecoxib, a COX-2 inhibitor, reduces papilloma cell proliferation, increases apoptosis and reduces HPV E6 and E7 expression. A pilot study of celecoxib therapy showed 2 of 3 patients with complete disease remission. We have now conducted a doubleblind placebo-controlled phase II clinical trial of the efficacy of celecoxib for RRP. Patients with moderate-tosevere disease were randomized to celecoxib or placebo for 1 year, then switched to the alternate treatment for 1 year. Surgery was performed every 3 months to remove all papilloma and assess rate of regrowth, with biopsies and blood collected at each surgery. Clinical response was defined as reduction in rate of regrowth of ≥50% for at least 6 months. Persistence of HPV was measured by qPCR. Fifty-one patients were enrolled, 33 competed the study. 64% had HPV6 and 36% had HPV11. 36% of patients improved on celecoxib, but there was no statistical difference between treatment and placebo groups. The rate of spontaneous improvement was much greater than expected. There was no correlation between Citation: Dr. Mark Shikowitz, Clinical trial of celecoxib for recurrent respiratory papillomatosis. Journal of Plastic Surgery and Case Studies Clinical trial of celecoxib for recurrent respiratory papillomatosis Mark Shikowitz The Feinstein Institute of Medical Research, USA. HPV type, duration of disease, gender, other demographic characteristics or celecoxib plasma levels and response. Patients with complete response still had latent HPV DNA in their airway epithelium. Immunology studies are in progress. In conclusion, we suspect celecoxib at this dose alone is not an effective treatment of RRP. However, combined with properly performed frequent surgery may positively impact immune response and the course of the disease.

Comparing the Safety and Efficacy of Celecoxib for the Treatment of Osteoarthritis in Asian and non-Asian Populations: An Analysis of Data from Two Randomized, Double-blind, Placebo-controlled, Active-comparator Trials.

IntroductionCelecoxib is an effective treatment for pain associated with osteoarthritis. There are differences in patient demographics among ethnic groups, with Asian populations typically smaller in body size. As a consequence, there may be a perception that celecoxib is less effective, or has poorer tolerability in Asian patients.MethodsThis analysis compares data from two multicenter, randomized, double-blind, placebo-controlled, active-comparator trials of celecoxib for the treatment of osteoarthritis of the knee: one study in Asian patients and the other in a mixed population comprised mostly of non-Asian patients (from which Asian patients were excluded for this analysis). Each trial was of similar design, with patients randomized 2:2:1 to 6 weeks treatment with celecoxib 200 mg once daily, active comparator (naproxen 500 mg twice daily or ibuprofen 800 mg three times daily), or placebo. The primary efficacy endpoint in each trial was the change from baseline to week 6 in the Patient’s Assessment of Arthritis Pain, as measured on a visual analog scale.ResultsIn total, 329 patients were included in the efficacy analysis, 179 in the Asian study and 150 in the non-Asian study. The Asian population was significantly older and smaller in body size (P < 0.0001). There was no significant difference between the Asian and non-Asian populations in change in pain score (95% confidence interval) at study endpoint with celecoxib [−1.1 (−7.7, 5.5); P = 0.7400] or placebo [−5.2 (−14.8, 4.4); P = 0.2870]. There were also no notable differences in safety outcomes between populations.ConclusionsDue to the smaller size of some Asian patients with OA, physicians may be tempted to decrease the dose of celecoxib below the therapeutic range recognized by regulatory authorities; these data suggest that dose changes are not necessary.FundingPfizer Inc.

Final Results of a Phase 3 Trial of Celecoxib (C) in Addition to Standard Chemotherapy for Advanced Non–Small Cell Lung Cancer With COX- 2 Overexpression: CALGB 30801 (Alliance)

Final Results of a Phase 3 Trial of Celecoxib (C) in Addition to Standard Chemotherapy for Advanced Non–Small Cell Lung Cancer With COX- 2 Overexpression: CALGB 30801 (Alliance)

A stratified randomized double-blind phase II trial of celecoxib for treating patients with cervical intraepithelial neoplasia: The potential predictive value of VEGF serum levels: An NRG Oncology/Gynecologic Oncology Group study

PurposeTo examine the effect of celecoxib on cervical intraepithelial neoplasia 3 (CIN 3). This is a NRG Oncology/Gynecologic Oncology Group study with translational biomarkers. Patients and methodsPatients with CIN 3 were randomized to celecoxib 400mg once daily (67 patients) or placebo (63 patients) for 14–18weeks. The primary outcome measure was histologic regression. A test of equal probabilities of success between two therapies was conducted, using Fisher's Exact Test at alpha=10% and 90% power when the treatment arm boosted the probability of success by 30%. Translational analysis included cervical tissue HPV genotyping, COX-2 expression in biopsies, and serum celecoxib and VEGF levels. ResultsIn primary analysis, histologic regression was not significantly higher in the celecoxib group (40%) than in the placebo group (34.1%). However, exploratory analyses suggest patients with high serum VEGF levels exhibited greater regression in the celecoxib arm (47.3%) than in the placebo arm (14.3%). Regression rates were similar by treatment group in patients with low VEGF. VEGF levels increased over time in the placebo group, but remained the same in the treatment group. COX-2 expression in cervical biopsies declined from pre-treatment to the end of treatment with celecoxib; it did not change with placebo. ConclusionsCelecoxib at 400mg once daily for 14–18weeks did not significantly decrease the severity of CIN 3 compared with placebo except, possibly, in subjects with high baseline VEGF. Therefore, serum VEGF levels might identify patients who may benefit from celecoxib or other therapies, personalizing future chemoprevention trials for CIN 3.

Minocycline and celecoxib as adjunctive treatments for bipolar depression: a study protocol for a multicenter factorial design randomized controlled trial.

BackgroundEvidence suggests that the use of anti-inflammatory agents may improve depressive symptoms in patients with bipolar affective disorder. However, there are few well-designed clinical trials demonstrating the efficacy of these newer treatment strategies.Patients and methodsThis is a multicenter, 3-month, randomized, placebo-controlled, double-blind, factorial design trial of minocycline and/or celecoxib added to TAU for the treatment of depressive symptoms in patients experiencing a DSM-5 bipolar I or II disorder and a current major depressive episode. A total of 240 participants will undergo screening and randomization followed by four assessment visits. The primary outcome measure will be mean change from baseline to week 12 on the Hamilton Depression Scale scores. Clinical assessments using the Clinical Global Impression scale, Patient Health Questionnaire-9, and the Generalized Anxiety Disorder 7-item scale will be carried out at every visit as secondary outcomes. Side-effect checklists will be used to monitor the adverse events at each visit. Complete blood count and plasma C-reactive protein will be measured at baseline and at the end of the treatment. Minocycline will be started at 100 mg once daily and increased to 200 mg at 2 weeks. Celecoxib will be started at 200 mg once daily and increased to 400 mg at 2 weeks.DiscussionAnti-inflammatory agents have been shown to be potentially efficacious in the treatment of depressive symptoms. The aim of this study is to determine whether the addition of minocycline and/or celecoxib to TAU improves depressive symptoms in patients with bipolar affective disorder.

A stratified randomized double-blind phase II trial of celecoxib in the treatment of patients with cervical intraepithelial neoplasia: A Gynecologic Oncology Group (GOG 0207) study with translational biomarkers and drug level monitoring

A stratified randomized double-blind phase II trial of celecoxib in the treatment of patients with cervical intraepithelial neoplasia: A Gynecologic Oncology Group (GOG 0207) study with translational biomarkers and drug level monitoring

An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis

Background and aimAlthough Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised...