NCCTG study N9741: Leveraging learning from an NCI cooperative group phase III trial

N9741 is a clinical trial in patients with metastatic colorectal cancer that was originally written in 1997 and completed patient accrual in 2004. One thousand seven hundred thirty-one patients were enrolled in the study. During the conduct of the trial, N9741 was repeatedly modified to adapt to toxicity findings, to add evaluation of oxaliplatin to what was originally a trial examining various schedules of irinotecan-based therapy, and to ask evolving questions. The trial led to a new U.S. Food and Drug Administration indication for 5-fluorouracil, leucovorin, and oxaliplatin as indicated for the treatment of previously untreated patients with metastatic colorectal cancer and helped to change the standard of care for the disease in the U.S. and worldwide. The data from the trial have been used to study multiple regimens, pharmacogenetics, and quality of life issues, to correlate plasma protein levels with outcomes, to inform trial methodology, and to perform economic analyses. To date nearly 30 papers and an even larger number of abstracts have been based upon data arising from the study. The history of the trial and the major findings are summarized in this review.