Adjuvant chemotherapy in pancreatic cancer

Abstract

Pancreatic cancer is one of the major causes of cancer death. Most patientspresent with advanced disease, and only 10-15% of patients can undergo resection. Survival after curative surgery is poor, as recurrences occur either locally ordistantly. Adjuvant therapy has been employed in large randomized trials to treatsystemic disease and hopefully improve the poor prognosis. Chemoradiation, chemotherapy using 5-fluorouracil/folinic acid (5FU/FA), S-1, gemcitabine orgemcitabine plus capecitabine, and combination therapy have all been used in theadjuvant setting. The results of the EORTC and ESPAC-1 trials have revealed that there is nosurvival advantage associated with adjuvant chemoradiation following resectionfor pancreatic cancer compared to no chemoradiation. There is no level 1 evidence, as yet that chemoradiation is superior to chemotherapy alone followingsurgery. Justification for the use of combination chemoradiation with follow-onchemotherapy is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. The RTOG9704 combination study did not demonstrate a survival difference between a5FU-based regimen compared with a gemcitabine-based chemoradiation regimen. There is no completed randomized study comparing chemotherapy versuscombination therapy. There is a clear survival advantage with adjuvant 5FU/FA and single-agentgemcitabine based on the results from the ESPAC-1 and CONKO-001 study, respectively. The ESPAC-3 trial showed that these adjuvant regimens are equallyeffective, but gemcitabine has a better toxicity profile. In contrast, in a Japanesepopulation, the JASPAC-01 trial demonstrated the superiority of S1 overgemcitabine. Adjuvant combination chemotherapy with gemcitabine plus capecitabinehas been recently shown to provide a survival advantage compared withgemcitabine alone in Western patients in the ESPAC-4 trial. Phase III studiesinvestigating other combination chemotherapy regimens are ongoing and willpossibly increase the number of treatment options in this setting.