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The GFF regimen is a combination chemotherapy protocol consisting of gemcitabine, 5-fluorouracil (5-FU), and folinic acid (leucovorin). Developed and extensively studied by the **CONKO-Studiengruppe** (Charité Onkologie study group), this regimen was designed specifically for the treatment of advanced pancreatic cancer. Gemcitabine acts as a nucleoside analog that inhibits DNA synthesis by targeting ribonucleotide reductase. 5-fluorouracil is a pyrimidine analog that interferes with DNA and RNA synthesis, primarily through the inhibition of thymidylate synthase. Folinic acid is included as a biochemical modulator to enhance the binding of 5-FU to its target enzyme, thereby increasing its cytotoxic efficacy. The regimen was evaluated in multicenter Phase II and Phase III trials (notably the **CONKO-002** trial), where it was compared against gemcitabine monotherapy in patients with advanced disease.
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