FOLFIRINOX: A Small Step or a Great Leap Forward?

Clinical trials in advanced pancreatic cancer during the last cou-pleofdecadeshavealmostuniformlyyieldeddisappointing results.To date, theparadigm for almost all phase III studies has been to compare the long-time reference standard, gemcitabine, with a gemcitabine-based combination regimen. Agents evaluated in combination with gemcitabine have been myriad; these have included both cytotoxic drugs (platinumanalogs, fluoropyrimidines, and camptothecins) and targeted therapies (inhibitors of farnesyl transferase, matrix metallo-proteinase, vascular endothelial growth factor, and epidermal growth factor receptor, to name a few). With the exception of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib—which produced amodest incremental improvementwhenadded to gemcit-abine1—none of these individual trials demonstrated a statistically significant survival benefit in favor of doublet therapy, although some have shown improvement in secondary outcome measures such a