Clinical Investigation: Gastrointestinal Cancer Preoperative Chemoradiation Therapy With Capecitabine/ Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study Emmanouil Fokas, MD, DPhil,* Lena Conradi, MD, y Christian Weiss, MD,* Thilo Sprenger, MD, y Peter Middel, MD, z Tillman Rau, MD, x Kathrin Dellas, MD, jj Julia Kitz, MD, { Franz Ro ¨del, PhD,* Rolf Sauer, MD, # Josef Ru ¨ schoff, MD,** Tim Beissbarth, PhD, yy Dirk Arnold, MD, zz B. Michael Ghadimi, MD, y Claus Ro ¨ del, MD,* and Torsten Liersch, MD y *Department of Radiation Therapy and Oncology, University of Frankfurt, Germany; y Department of General Surgery, University Medical Center of Go¨ttingen, Germany; z Institute for Pathology, University Medical Center, Go¨ttingen, Germany; x Institute of Pathology, University Hospital Erlangen, Erlangen, Germany; jj Department of Radiotherapy, Lu¨beck University, Germany; { Institute for Pathology, University Medical Center, Go¨ttingen, Germany; # Department of Radiation Oncology, University of Erlangen, Germany; **Targos Molecular Pathology, Kassel, Germany; yy Department of Medical Statistics, University Medical Center of Go¨ttingen, Germany; and zz Tumor Biology Center Freiburg, University of Freiburg, Germany Received Jul 6, 2013, and in revised form Sep 4, 2013. Accepted for publication Sep 8, 2013. Summary We previously showed that addition of cetuximab to chemoradiation therapy (CRT) failed to improve complete response rates (pCR) in patients with rectal cancer. However, early endpoints may not be coupled to longer-term outcomes. Here, we show that CRT combined with cetuximab is safe, feasible, Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxalipla- tin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetux- imab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (nZ45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS muta- tion status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (nZ4; pCR), I (nZ17), II (nZ10), III (nZ14), and IV (nZ8). For patients who underwent surgery (nZ53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, Reprint requests to: Emmanouil Fokas, MD, DPhil, Department of Radiotherapy and Oncology, Johann Wolfgang Goethe-University Frank- furt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Tel: (49) 69 6301 5047; E-mail: emmanouil.fokas@kgu.de C. Ro ¨del and T. Liersch contributed equally to this report and study. This study was supported in part by grants from Merck Pharma GmbH, Darmstadt, Germany, Hoffmann-La Roche AG, Grenzach-Wyhlen, Germany, and Sanofi-Aventis Pharma GmbH, Berlin, Germany. Conflict of interest: Claus Ro ¨del received a research fund from Merck Pharma GmbH; Dirk Arnold and Claus Ro ¨del received speaker’s honoraria from Hoffmann-La Roche AG, and Sanofi-Aventis Pharma GmbH. Supplementary material for this article can be found at www.redjournal.org. Int J Radiation Oncol Biol Phys, Vol. 87, No. 5, pp. 992e999, 2013 0360-3016/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2013.09.011 Radiation Oncology International Journal of biology physics www.redjournal.org