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

Abstract

Purpose To 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 Methods Patients with CIN 3 were randomized to celecoxib 400 mg once daily (67 patients) or placebo (63 patients) for 14–18 weeks. 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. Results In 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. Conclusions Celecoxib at 400 mg once daily for 14–18 weeks 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.

The selective cyclooxygenase‐2 inhibitor mavacoxib (Trocoxil) exerts anti‐tumour effects in vitro independent of cyclooxygenase‐2 expression levels

“…With ample epidemiological evidence demonstrating an inverse correlation between NSAID use and the incidence and progression of cancer, there have been numerous trials attempting to validate these drugs for use as cancer therapeutics. Aspirin, celecoxib, ibuprofen and piroxicam have all demonstrated positive anti‐neoplastic effects during clinical trials . However, the use of these drugs for cancer prevention and therapy remains controversial.…”

“…Aspirin, celecoxib, ibuprofen and piroxicam have all demonstrated positive anti-neoplastic effects during clinical trials. 76,[84][85][86][87][88][89][90] However, the use of these drugs for cancer prevention and therapy remains controversial. Many clinical studies have not indicated a significant benefit to the patient, and in combination with the side-effects associated with NSAIDs (which can range from moderate GI toxicity to severe cardio toxicity), there is limited enthusiasm for their use.…”

New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress

“…Another recent research focused on the assessment of celecoxib efficacy in patients with CIN 3, a stage in which regression is unlikely. The results showed that celecoxib 400 mg/day for 14–18 weeks did not decrease the degree of dysplasia, except for patients with an increased baseline level of vascular endothelial growth factor (VEGF), suggesting that VEGF may be used as a marker for detecting patients who could benefit from that type of treatment [ 84 ].…”

Curbing Lipids: Impacts ON Cancer and Viral Infection

“…Since viral infection associated cancers also heavily utilize lipid metabolism for their growth and progression, therefore there could be common targets which could be tested to combat viral cancers. Numerous studies discuss and show promising results targets for NSAIDs [116,162,163,164,165,166,167,168], mTOR pathway regulators [169,170,171,172], and FASN inhibitors [75] in viral infection associated cancers but additional in vivo studies need to be done to fully exploit these pathways. These studies support the further development of statins, FASN inhibitors, fibrates, and NSAIDs as potential anticancer agents.…”