Clinical Outcome of the ACCORD 12/0405 PRODIGE 2 Randomized Trial in Rectal Cancer Jean-Pierre Ge ´rard, David Azria, Sophie Gourgou-Bourgade, Isabelle Martel-Lafay, Christophe Hennequin, Pierre-Luc Etienne, Ve ´ronique Vendrely, Eric Franc ¸ois, Guy de La Roche, Olivier Bouche ´, Xavier Mirabel, Bernard Denis, Laurent Mineur, Jean-Franc ¸ois Berdah, Marc-Andre ´ Mahe ´, Yves Be ´couarn, Olivier Dupuis, Ge ´rard Lledo, Jean-Franc ¸ois Seitz, Laurent Bedenne, Be ´ata Juzyna, and Thierry Conroy Author affiliations appear at the end of this article. Submitted April 6, 2012; accepted August 31, 2012; published online ahead of print at www.jco.org on October 29, 2012. Supported in part by Roche and sanofi- aventis along with a grant from the French National Research Program: Programmes hospitaliers de recherche clinique; the trial was conducted under the auspices of the Institut National du Cancer. Presented in oral and abstract form at the 53rd Annual Meeting of the Ameri- can Society of Radiation Oncology, Miami, FL, October 2-6, 2011, and the American Society of Clinical Oncology GI Cancers Symposium, San Francisco, CA, January 19-21, 2012. The funding sources for the study had no role in the study design, data collec- tion, data analysis, data interpretation, or writing of the report. The principal investigator had full access to all the raw data in the study and was respon- sible for drafting and submission for publication. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Clinical trial information: NCT002133-39 Corresponding author: Jean-Pierre Ge ´ rard, MD, Centre Antoine Lacassa- gne, 33 avenue de Valombrose, 06189 Nice Cedex 2-France; e-mail: jean-pierre.gerard@nice.unicancer.fr. © 2012 by American Society of Clinical Oncology 0732-183X/12/3036-4558/$20.00 DOI: 10.1200/JCO.2012.42.8771 A B S T R A C T Purpose The ACCORD 12 trial investigated the value of two different preoperative chemoradiotherapy (CT-RT) regimens in T3-4 Nx M0 resectable rectal cancer. Clinical results are reported after follow-up of 3 years. Patients and Methods Between November 2005 and July 2008, a total of 598 patients were randomly assigned to preoperative CT-RT with CAP45 (45-Gy RT for 5 weeks with concurrent capecitabine) or CAPOX50 (50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin). Total mesorectal excision was planned 6 weeks after CT-RT. The primary end point was sterilization of the operative specimen, which was achieved in 13.9% versus 19.2% of patients, respectively ( P  .09). Clinical results were analyzed for all randomly assigned patients according to the intention-to-treat principle. Results At 3 years, there was no significant difference between CAP45 and CAPOX50 (cumulative incidence of local recurrence, 6.1% v 4.4%; overall survival, 87.6% v 88.3%; disease-free survival, 67.9% v 72.7%). Grade 3 to 4 toxicity was reported in four patients in the CAP45 group and in two patients in the CAPOX50 group. Bowel continence, erectile dysfunction, and social life disturbance were not different between groups. In multivariate analysis, the sterilization rate (Dworak score) of the operative specimen was the main significant prognostic factor (hazard ratio, 0.32; 95% CI, 0.21 to 0.50). Conclusion At 3 years, no significant difference in clinical outcome was achieved with the intensified CAPOX regimen. When compared with other recent randomized trials, these results indicate that concurrent administration of oxaliplatin and RT is not recommended. J Clin Oncol 30:4558-4565. © 2012 by American Society of Clinical Oncology INTRODUCTION Since the pivotal German 1 and Dutch 2 trials, preoper- ative chemoradiotherapy (CT-RT) and short-course preoperative RT 3 have been introduced in T3-4 Nx M0 resectable rectal cancer in the routine practice of most institutions. The FFCD (Fédération Francophone de la Cancérologie Digestive) 9203 4 and EORTC (European Organisation for Research and Treatment of Cancer) 22921 5 trials demonstrated that the concurrent addi- tion of fluorouracil (FU) and folinic acid to RT in- creased sterilization of the operative specimen (complete sterilization of operative specimen [ypCR], 11%) and reduced the risk of local recur- rence (8% at 5 years) without survival benefit. The ACCORD (Actions Concertées dans les Can- cers Colorectaux et Digestifs) 12 trial was designed and initiated in 2005 using a pragmatic approach to test concurrently the relevance of radiation dose escalation (50 v 45 Gy over 5 weeks), addition of concurrent ox- aliplatin, and use of capecitabine to replace FU (CA- POX50 [50-Gy RT for 5 weeks with concurrent capecitabine and oxaliplatin] group). The control group (CAP45) received 45-Gy RT for 5 weeks with concurrent capecitabine. The primary end point was ypCR, and the results (19.2% v 13.9%; P  .09) showed no significant benefit of the CAPOX50 regimen for this end point. 6 The primary aim of this article is to report the clinical outcome of these patients (local and distant recurrence, overall and disease-free survival [DFS], toxicity, and bowel function), which was analyzed at 3 years as a secondary end point. PATIENTS AND METHODS Patients Details of the patients and methods have been re- ported previously. 6 In short, inclusion criteria were as fol- lows: resectable adenocarcinoma of the rectum, accessible JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 30  NUMBER 36  DECEMBER 20 2012 4558 © 2012 by American Society of Clinical Oncology Downloaded from ascopubs.org by 18.215.175.143 on June 7, 2022 from 018.215.175.143 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.