Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2224
Revised: December 13, 2013
Accepted: January 3, 2014
Published online: March 7, 2014
While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.
Core tip: No standard of care exists for patients with advanced pancreatic cancer who have progressed on front-line chemotherapy. To date, most available evidence has come from small non-randomized studies, with efficacy results that have been fairly dismal. In this review, we discuss both traditional and novel cytotoxic and targeted therapies that have been evaluated in this refractory setting and how they may (or may not) be applicable to clinical practice; and raise considerations for clinical trial design in the future, particularly in this current era of both expanding chemotherapeutic options and molecular/“precision” medicine.