Heinrich et al. BMC Cancer 2011, 11:346 http://www.biomedcentral.com/1471-2407/11/346 Background Mortality rates of pancreatic surgery have dramatically decreased to less than 2% in experienced centers during the last decades. Despite these improvements in the perioperative outcome, long-term survival of patients with pancreatic cancer remains limited with only 12 months median survival reported from pure surgical series [1]. Similar to other gastrointestinal cancers, several adju- vant treatment concepts have been tested in the past to improve long-term outcome. After controversial results from initial chemoradiation trials [2,3] recent rando- mized trials demonstrate a significant prolongation of disease-free and overall survival by adjuvant chemother- apy [4-6]. While gemcitabine (Gem) and 5-fluorouracil (FU)/folinic acid (FA) are equally effective, adjuvant Gem is less toxic than 5-FU/FA [7]. Therefore, adjuvant chemotherapy with Gem should presently be considered the standard of care after a curative resection of pan- creatic cancer. The major disadvantage of adjuvant che- motherapy is, however, that a large proportion of patients (> 20%) cannot receive any treatment [2,8,9], mainly due to the surgical morbidity of pancreatic surgery [10]. In contrast, a preoperative (neoadjuvant) treatment can be applied to almost all patients since it is indepen- dent of the surgical morbidity. The safety of this con- cept has been demonstrated in a recent phase II trial: 28 patients with resectable cancer of the pancreatic head received gemcitabine and cisplatin (GemCis) for two months before resection. This treatment was well toler- ated with only a few grade III toxicities and al low surgi- cal morbidity rate [11]. Furthermore, a significant Page 2 of 7 histological and cytological response was documented resulting in a median survival of 26.5 months [12]. Interestingly, more than 40% of the patients were mal- nourished at study entry, and the nutritional status of these patients improved significantly during neoadjuvant chemotherapy [13]. In addition, neoadjuvant chemother- apy may decrease the amount of circulating tumor cells and intraoperative tumor spillage as demonstrated for several tumor entities [14]. Similar survival results have been reported from a recent phase II trial, in which patients with locally unre- sectable pancreatic cancer received a down-sizing che- motherapy with Gem and oxaliplatin (Ox): fourty percent of these patients finally underwent resection, and the R0 resection rate was 70% [15]. Following these encouraging results, this randomized phase III study was initiated to further investigate the efficacy of neoadjuvant chemotherapy for resectable can- cer of the pancreatic head. Methods/Design This is a randomized controlled phase III trial organized by the Swiss HPB-center at the University Hospital of Zurich. The study protocol has been approved by the Ethical Review Board of the University Hospital of Zur- ich and the Swiss national authorities. Each approved country has a national main investigator for the coordi- nation of the national centers. Eligible patients are randomized (1:1) to either receive the standard treatment (pancreaticoduodenect- omy and adjuvant chemotherapy) or neoadjuvant chemotherapy followed by this standard treatment (Figure 1). Figure 1 Schematic description of the NEOPAC trial. Patients are randomized to either receive the standard treatment (surgery+adjuvant chemotherapy) or neoadjuvant chemotherapy followed by the standard treatment.