Neoadjuvant treatment for resectable pancreatic cancer: time for phase III testing?

This paper discusses the rationale for phase III testing of neoadjuvant therapy in patients affected by resectable pancreatic adenocarcinoma. The therapeutic management of patients affected by resectable pancreatic cancer is particularly troublesome due to the aggressiveness of the disease and to the limited efficacy and sometimes unfavourable risk-benefit ratio of the available therapeutic tools. Conflicting data on the role of adjuvant chemoradiation have been reported, while adjuvant single-agent chemotherapy significantly improved overall survival (OS) when compared to surgery alone. However, the OS figures for adjuvant chemotherapy remain disappointing. In effect, pancreatic cancer exhibits a prominent tendency to recur after a brief median time interval from surgery and extra-pancreatic dissemination represents the predominant pattern of disease failure. Neoadjuvant treatment has a strong rationale in this disease but limited information on the efficacy of this approach is available from single arm trials with low levels of evidence. Thus, in spite of two decades of investigation there is currently no evidence to support the routine use of pre-surgical therapy in clinical practice. To foster knowledge on the optimal management of this disease, and to produce evidence-based treatment guidelines, there is no alternative to well designed randomized trials. Systemic chemotherapy is a candidate for testing because it is supported by a more robust rationale than chemoradiation. Combination chemotherapy regimens with elevated activity in advanced disease warrant investigation. Caution would suggest the running of an exploratory phase II randomized trial before embarking on a large phase III study.