Is There a Best Radiosensitizing Agent in the Treatment of Locally Advanced Rectal Cancer?

Over the past several decades, the management of localized rectal cancer has evolved from surgery alone as the definitive treatment to incorporating both radiation and chemotherapy to improve rates of local control and disease-free survival. Several chemoradiation regimens have been tested with different mechanisms of action, efficacy, and toxicity. There is little debate that concurrent radiation and a fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine) is the current standard of care prior to total mesorectal excision (TME). Attempts to add additional chemotherapy, such as oxaliplatin or irinotecan, have not consistently improved results. Recent attention has been given to concurrent biologic therapies (vascular endothelial growth factor (VEGF)-, epidermal growth factor receptor (EGFR)-, Poly(ADP-ribose) polymerase (PARP)-inhibitors, etc.) which may improve the outcomes of multi-modality therapy; however, the evidence is limited to phase I/II trials. It is critical for oncologists to be aware of various radiosensitizing agents that have been investigated and which will provide the best chance of disease control. In this review, we describe the mechanisms of action and evidence supporting these regimens to determine if there is a best radiosensitizing agent. Furthermore, we describe the relevant studies investigating the recent use of biologic radiosensitizers and the future direction using those agents.