Eicosanoid Modulation in Advanced Lung Cancer: Cyclooxygenase-2 Expression Is a Positive Predictive Factor for Celecoxib + Chemotherapy—Cancer and Leukemia Group B Trial 30203
Abstract
PURPOSE: Increased expression of eicosanoids in cancer has been associated with adverse prognosis. We performed a randomized phase II trial to test the hypothesis that inhibitors of two eicosanoid pathways (cyclooxygenase-2 [COX-2], celecoxib and 5-lipoxygenase [5-LOX], zileuton) added to chemotherapy would improve outcome in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC, a performance status of 0 to 2, and no prior therapy were eligible. All patients received carboplatin area under the curve (AUC) 5.5 mg/mL x min day 1 + gemcitabine (1,000 mg/m(2)) days 1 and 8. Patients were randomly assigned to: (a) zileuton 600 mg PO qid, (b) celecoxib 400 mg PO bid, or (c) celecoxib and zileuton at the same doses. Immunohistochemical staining for COX-2 and 5-LOX was performed without knowledge of outcomes. RESULTS: One hundred forty patients were entered and 134 were eligible and treated. There was no survival difference between the arms. COX-2 expression was a negative prognostic marker for overall survival (OS; hazard ratio [HR] = 2.51, P = .019 for index >or= 4; HR = 4.16, P = .005 for index = 9) for patients not receiving celecoxib. Patients with increased COX-2 expression (index >or= 4), receiving celecoxib had better survival than did COX-2-expressing patients not receiving drug (HR = .342, P = .005 for OS; HR = .294, P = .002 for failure-free survival). Multivariate analysis confirmed the interaction of COX-2 and celecoxib on…
How strong is the evidence?
Evidence Hub reads this as a randomized trial. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial
- Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease
- Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience
- Celecoxib or naproxen treatment does not benefit depressive symptoms in persons aged 70 and over: findings from a randomized controlled trial
- Comparative Clinical Effectiveness of Nonsurgical Treatment Methods in Patients With Lumbar Spinal Stenosis: A Randomized Clinical Trial
- Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.