658 Strahlenther Onkol 2010 · No 12 © Urban & Vogel Induction Chemotherapy before Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer Is It Time for a Randomized Phase III Trial? Claus Rödel 1 , Dirk Arnold 2 , Heinz Becker 3 , Rainer Fietkau 4 , Michael Ghadimi 3 , Ullrich Graeven 5 , Clemens Hess 6 , Ralf Hofheinz 7 , Werner Hohenberger 8 , Stefan Post 9 , Rudolf Raab 10 , Rolf Sauer 4 , Frederick Wenz 11 , Torsten Liersch 3 Review Article Strahlentherapie und Onkologie 1 Klinik für Strahlentherapie und Onkologie, Universität Frankfurt, Frankfurt am Main, Germany, 2 Klinik und Poliklinik für Innere Medizin IV, Universität Halle, Halle, Germany, 3 Klinik für Allgemein- und Visceralchirurgie; Universität Göttingen, Göttingen, Germany, 4 Strahlenklinik, Universität Erlangen, Erlangen, Germany, 5 Klinik für Hämatologie, Onkologie und Gastroenterologie, Kliniken Maria Hilf GmbH, Mönchengladbach, Germany, 6 Klinik für Strahlentherapie und Radioonkologie, Universität Göttingen, Göttingen, Germany, 7 III. Medizinischen Klinik Hämatologie und Internistische Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany, 8 Chirurgische Klinik, Universität Erlangen, Erlangen, Germany, 9 Chirurgische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany, 10 Klinik für Allgemein- und Visceralchirurgie; Klinikum Oldenburg, Oldenburg, Germany, 11 Klinik für Strahlentherapie und Radioonkologie, Universitätsmedizin Mannheim, Mannheim, Germany. Received: May 7, 2010; accepted: September 27, 2010 Published online: November 30, 2010 Background: In the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of dis- tant 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 Methods: This review article focuses on phase II–III trials designed to improve 5-fluorouracil (5-FU)-based com- bined 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. Results: After preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemothera- py, 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. Conclusion: Whether 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. Key Words: Rectal cancer · Induction chemotherapy · Chemoradiotherapy Strahlenther Onkol 2010;186:658–64 DOI 10.1007/s00066-010-2194-2 Induktionschemotherapie vor Radiochemotherapie und Operation beim lokal fortgeschrittenen Rektumkarzinom: Zeit für eine randomisierte Phase-III-Studie? Hintergrund: Nach Einführung der präoperativen Radiochemotherapie (RCT) und der totalen mesoerektalen Excision manifes- tieren sich Rezidive beim Rektumkarzinom am häufigsten als Fernmetastasen. Daher ist die Integration einer systemisch effek- tiveren Therapie in das multimodale Behandlungskonzept derzeit die entscheidende Herausforderung. Die Frage ist, wann und wie diese Systemtherapie mit adäquater Dosis und Intensität verabreicht werden kann.