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Copyright ©2012 Baishideng Publishing Group Co.
World J Gastroenterol. Apr 14, 2012; 18(14): 1565-1572
Published online Apr 14, 2012. doi: 10.3748/wjg.v18.i14.1565
Table 1 Staging of pancreatic cancer
StageTNM classificationClinical classification5-year percent survival (mo)
Stage 0TisN0M0Resectable
StageIAT1N0M0Initial31.4
StageIBT2N0M027.2
Stage IIAT3N0M015.7
Stage IIBTXN1M0Locally advanced7.7
Stage IIIT4NXM06.8
Stage IVTXNXM1Metastatic2.8
Table 2 Mode of action of principal drugs used in pancreatic cancer
AgentMode of action
5-FU5-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 analoguesPlatinum 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
TaxanesThe 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