Neoadjuvant Treatment for Pancreatic Cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective therapeutic options and exceedingly high mortality rates. Currently, cure can only be achieved through resection, however the vast majority of patients present with advanced disease for which upfront surgery is not an option. In an effort to improve surgical candidacy, neoadjuvant chemotherapy, with or without radiation therapy, is often used in an effort to downstage borderline resectable and locally advanced tumors, and some argue for its use even in patients with resectable tumors. Underlying this thinking is the recognition that pancreatic cancer is simultaneously both a locally invasive and systemic disease, even in patients without evidence of metastasis on imaging. Current evidence to date is largely retrospective, but suggests that neoadjuvant therapy can increase R0 (pathologically negative margin) resection rates and improve overall survival. The standard approach to neoadjuvant treatment involves choosing between the two most active combination regimens for metastatic disease, namely modified FOLFIRNOX and gemcitabine/nab-paclitaxel. Nonrandomized data indicate that these regimens can yield resection rates up to 68% and 36%, in borderline resectable and locally advanced PDAC, respectively. Furthermore, randomized data in patients with resectable PDAC treated with gemcitabine-based neoadjuvant therapy suggests that despite an approximate 10% drop in resection rates, there is a significant improvement in median overall survival. Herein, we will discuss the rationale for neoadjuvant therapy, current and former treatment regimens, common issues faced by clinicians when using these combinations, and several ongoing clinical trials.