The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35–0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08–1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725–0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI=1.03–1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09–1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Stabilization of E-cadherin adhesions by COX-2/GSK3β signaling is a targetable pathway in metastatic breast cancer

“…COX-2/PGE2 is an attractive therapeutic target, as it acts on multiple cell types within cancers and can also be induced by conventional chemotherapy ( 54 , 72 ). Combination of celecoxib with other chemotherapies including taxanes have been tested in preclinical models and clinical trials and showed some indication of efficacy ( 73 , 74 ). However, these trials revealed an unmet need for biomarkers to better identify which cancers may respond to combination treatments that include celecoxib ( 75 , 76 ).…”

Non-canonical non-genomic morphogen signaling in anucleate platelets: a critical determinant of prothrombotic function in circulation

“…Molecules targeting Wnt pathway such as PRI-724 [ 163 ] (a β-catenin antagonist), LGK-974 [ 164 ] (a porcupine inhibitor) and Vantictumab [ 165 ] (an anti-FZD antibody) are in early clinical trials for the treatment of leukemia, melanoma, colorectal carcinoma and cancers of breast, lung, and pancreas [ 118 ]. In addition, two FDA-approved non-steroidal anti-inflammatory drugs (NSAIDs), namely sulindac [ 166 ], that also targets DVL, and celecoxib [ 167 ], that also inhibits β-catenin signaling, are under early clinical trials for their antineoplastic activity.…”

Deciphering the roles of myeloid derived suppressor cells in viral oncogenesis

“…PGE2 induces arginase expression in a mouse model of lung cancer and inhibiting COX-2 can lead to a lymphocyte-mediated anti-tumour response ( 242 ). A large meta-analysis, across multiple tumour types, showed modest benefits ( 238 ) in adding the selective COX-2 inhibitor celecoxib to standard anticancer therapy with no concerning toxicity ( 230 ). Celecoxib has been used in a phase I trial combined with radiotherapy in NPC with encouraging outcomes and no clear toxicity, however, this trial did not report on the effect of EBV positive versus negative tumours or look at MDSC numbers or function ( 243 ).…”