• Claus Rödel, Dirk Arnold, Heinz Becker, Rainer Fietkau, Michael Ghadimi, Ullrich Graeven, Clemens Hess, Ralf Hofheinz, Werner Hohenberger, Stefan Post, Rudolf Raab, Rolf Sauer, Frederick Wenz, and Torsten Liersch.
• Klinik für Strahlentherapie und Onkologie, Universität Frankfurt, Frankfurt am Main, Germany. claus.roedel@kgu.de
• Strahlenther Onkol. 2010 Dec 1; 186 (12): 658-64.

Backgroundin the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity.Material And Methodsthis review article focuses on phase II-III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings.Resultsafter preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal, or investigator's discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease.Conclusionwhether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial.

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