Adjuvant and neoadjuvant treatment in pancreatic cancer

Table 2 Mode of action of principal drugs used in pancreatic cancer

Agent	Mode of action
5-FU	5-FU is a folate antimetabolite that forms a ternary complex involving 5-fluoro-2-deoxyuridine-5-monophosphate, thymidylate synthase, and 5,10-methylene THF. The formation of this complex thereby inhibits thymidylate synthase activity, which subsequently depletes intracellular thymidylate levels and ultimately suppresses DNA synthesis Also, two metabolites of 5-FU, 5-fluoro-2-deoxyuridine-5-triphosphate and 5-fluorouridine-5-triphosphate, can be incorporated into DNA and RNA, respectively, resulting in DNA instability and interfering with RNA processing and function
Gemcitabine (Gemzar®)	Gemcitabine is an S-phase nucleoside analogue (diflourodeoxycytidine) that is phosphorylated to difluorodeoxycytidine triphosphate by deoxycytidine kinase. Gemcitabine also stimulates deoxycytidine kinase and inhibits both ribonucleotide reductase and deoxycytidine monophosphate deaminase. Gemcitabine triphosphate is incorporated into nascent DNA to inhibit DNA synthesis
Capecitabine (Xeloda®)	Capecitabine an oral, tumor-selective fluoropyrimidine carbamate that is sequentially converted to 5-FU by three enzymes located in the liver and in tumors. The final step is the conversion of 5′-deoxy-5-fluorouridine to 5-FU by thymidine phosphorylase in tumors
Platinum analogues	Platinum forms adducts with DNA inhibiting transcription and replication causing cell death. Oxaliplatin is a third-generation platinum analogue (a diaminocyclohexane platinum derivative) that may have activity in tumors resistant to cisplatin or carboplatin and may have an additive/synergistic activity in doublet or triplet therapy
Taxanes	The taxanes include paclitaxel and docetaxel (Taxotere®) and are semi-synthetic microtubule inhibitors with a different mechanism of action from the vinca alkaloids. Taxanes bind to β-tubulin, promoting microtubule assembly and preventing depolymerisation thus forming stable non-functional complexes and inhibiting the function of the mitotic spindle; This results in cell cycle arrest and increased sensitivity to radiation
Irinotecan CPT11, Camptosar®)	Irinotecan is a topoisomerase I inhibitor that impedes the DNA helix tortional stress-relieving activity of DNA topoisomerases and also prevents their release from the DNA thus prompting apoptosis

5-FU: 5-fluorouracil.