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A three-drug anticancer regimen combining the nucleoside analog antimetabolite gemcitabine, the platinum-based DNA crosslinking agent cisplatin, and the selective cyclooxygenase-2 inhibitor celecoxib. Gemcitabine inhibits DNA synthesis after intracellular phosphorylation to active nucleotides, leading to apoptosis in dividing cells. Cisplatin forms DNA crosslinks causing replication arrest and cell death. Celecoxib inhibits COX-2, potentially modulating tumor-promoting inflammation and sensitizing tumors to chemotherapy. Clinically evaluated as an investigational combination in metastatic pancreatic cancer and as neoadjuvant therapy for muscle-invasive urothelial bladder cancer; a phase II pancreatic trial using fixed-dose-rate gemcitabine plus cisplatin with continuous celecoxib did not show increased activity over the doublet, with notable neutropenia. Routes have included intravenous gemcitabine and cisplatin with oral celecoxib.[1][7][8]
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