Lay Summary: About NSABP-04
NSABP R-04 is “A Clinical Trial Comparing Preoperative Radiation Therapy and Capecitabine with or without Oxaliplatin with Preoperative Radiation Therapy and Continuous Intravenous Infusion of 5-Fluorouracil with or without Oxaliplatin in the Treatment of Patients with Operable Carcinoma of the Rectum. The primary objective is to compare the rate of local-regional relapse in patients with resectable rectal cancer treated with chemoradiotherapy comprising radiation therapy and either capecitabine or fluorouracil with or without oxaliplatin; there are 9 secondary objectives.
The investigators of the NSABP R-04 trial have been working diligently for years to launch their important study evaluating the role of oral fluoropyrimidine-based neoadjuvant chemoradiotherapy. The lengthy clinical trial development process outlined above has exposed the NSABP R-04 trial to external factors beyond the investigators’ control (in particular, to corporate and US Food and Drug Administration decisions) that have caused its design to be changed and delayed its activation. Now, the emergence of new data in the adjuvant treatment of colorectal cancer (the Xeloda in Adjuvant Colon Cancer Therapy [X-ACT] trial2 and the MOSAIC trial3) has diminished the novelty of the original question posed by the NSABP R-04 trial but strengthened the concept of neoadjuvant chemoradiotherapy (the German Rectal Cancer Study). The trend toward improved disease-free survival for capecitabine in the X-ACT trial, suggests strongly that capecitabine is an appropriate treatment to examine in R-04, and the demonstration of improved disease-free survival in adjuvant colon cancer for an oxaliplatin containing regimen in the MOSAIC trial mandates the consideration of an oxaliplatin regimen in rectal cancer.
In summary, this is a trial that poses a number of important questions. Until they are resolved, properative chemo-radiation with xeloda and oxapliplatin containing regimens remain experimental, even though they are already being used in the clinic.