Neoadjuvant chemoradiation for rectal cancer: is more better?

Neoadjuvant chemoradiation is now considered the clear preferable adjuvant standard of care in the management of stage II/III rectal cancer. Neoadjuvant fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU plus radiation therapy. Recent nonrandomized comparative studies have shown that capecitabine (Xeloda) plus radiation result in downstaging and pathologic complete responses equivalent to those of 5-FU plus radiation, making this combination an acceptable alternative neoadjuvant treatment. The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy appears to result in more favorable pathologic responses in phase I/II trials. These combinations should be investigated further in larger phase III studies before they are endorsed in the routine neoadjuvant treatment of rectal cancer. This article will review the progress of chemoradiation over the past 2 decades, current standards of care, and investigational treatments in the neoadjuvant treatment of rectal cancer.