From the Department of Radiation Therapy, University of Frankfurt am Main, Germany
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to Claus Rödel, MD, Department of Radiation Therapy, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; e-mail: claus.roedel{at}kgu.de
Overview: With optimized local treatment achieved through preoperative radiotherapy or chemoradiotherapy and total mesorectal excision, the development of distant metastases is now the predominant mode of failure in rectal cancer. The challenge is to integrate more effective systemic therapy into combined modality programs. Capecitabine, oxaliplatin, irinotecan, as well as targeted therapies, improved results for patients with colorectal cancer in the metastatic and adjuvant settings. These agents have now been incorporated into phase I and II rectal cancer studies as well. Higher pathologic complete response (pCR) rates in the range of 15% to 30% have been achieved with these novel combinations. However, pCR is an early surrogate endpoint that may not necessarily translate into improved long-term outcomes. For some studies, increased pCR is associated with an increase in acute toxicity; data on long-term toxic sequelae are not yet available. Defining the best sequence of combinations (including neoadjuvant combination chemotherapy before chemoradiotherapy), the role of postoperative chemotherapy, and the optimal sequence of targeted therapies are some of the challenges that remain. Phase III trials are ongoing to determine whether these novel combination regimens offer an advantage compared with standard 5–FU-based chemoradiotherapy.
