Leveraging learning from a phase III colorectal cancer clinical trial: outcomes, methodology, meta-analysis and pharmacogenetics.

This paper summarizes the results of a National Cancer Institute (NCI) sponsored Phase III clinical trial led by the North Central Cancer Treatment Group (NCCTG) that enrolled patients with metastatic colorectal cancer (MCRC) on combination chemotherapy regimens in the late 1990s through 2003. The study changed clinical practice in the US and led to a new Food and Drug Agency (FDA) indication for the drug oxaliplatin. The time was opportune in the management of MCRC, when, after 50 years of using the single active agent 5-Fluorouracil (5-FU), two new cytotoxic agents, irinotecan and oxaliplatin, were found to be active in MCRC. Patients were randomized to receive two of those three agents in each arm of the trial. Over 500 of the >1700 enrolled patients permitted their germline DNA and plasma samples to be banked. Consequently this is one of the largest cancer populations available for pharmacogenetic studies and for the study of other biomarkers. Data derived from N9741 led to publications related to treatment of MCRC and trial methodology, used pooled meta-analyses and helped to pioneer the field of pharmacogenetics. This review highlights some of those observations. Initiated in 1997, the trial has spawned 26 published or in press papers and 39 abstracts.