Current status of radiosensitizing agents for the management of rectal cancer.

The management of locally advanced rectal cancer requires a multidisciplinary effort. Surgical resection remains the therapeutic cornerstone, but neoadjuvant chemoradiation clearly improves both surgical and long-term outcomes. Pathological complete response is a desirable outcome and has been associated with good long-term outcomes. This article provides an overview of the evolution and current role of radiosensitizing chemotherapy when given as part of neoadjuvant chemoradiation for locally advanced rectal cancer. 5-fluorouracil, given either as an infusion or orally as capecitabine, appears to have the most favorable balance of efficacy and tolerability at the present time. Oral administration without need for central IV access makes capecitabine an attractive option. Oxaliplatin and irinotecan have demonstrated increased toxicity without substantial associated improvement in outcomes. Both bevacizumab and cetuximab appear feasible when given with radiosensitizing chemotherapy, but no strong signal of improved efficacy has been demonstrated so far. There is currently a great need for new radiosensitizing agents and predictive biomarkers to help optimize the use of existing therapeutics. Increased topoisomerase I expression and increased EGFR gene copy number as possible predictors of response to irinotecan- and cetuximab-based chemoradiation, respectively, deserve further studies.