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Cisplatin + methotrexate + gemcitabine is a combination chemotherapy regimen being investigated for the treatment of unresectable malignant pleural mesothelioma (MPM). This specific protocol, developed and studied by the H. Lee Moffitt Cancer Center and Research Institute, utilizes transarterial chemoperfusion (TACP) to deliver the agents directly into the arterial supply of the pleura. The regimen combines three small molecule antineoplastics with complementary mechanisms: cisplatin, a platinum compound that induces DNA cross-linking; methotrexate, an antimetabolite that inhibits dihydrofolate reductase (DHFR); and gemcitabine, a nucleoside analog that inhibits DNA synthesis via ribonucleotide reductase and DNA polymerase. The localized TACP delivery method aims to achieve high regional drug concentrations while reducing systemic toxicity, addressing the therapeutic challenge of unresectable MPM.
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