Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: Results of the German CAO/ARO/AIO-04 randomized phase III trial.

Gastrointestinal (Colorectal) Cancer
Session Type and Session Title: 
Oral Abstract Session, Gastrointestinal (Colorectal) Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 3500)
Claus Rodel, Torsten Liersch, Rainer Fietkau, Werner Hohenberger, Ullrich Graeven, Torsten Hothorn, Dirk Arnold, Hans-Rudolf Raab, Christian Wittekind, Clemens F Hess, Ludger Staib, Heinz Becker, Rolf Sauer, German Rectal Cancer Study Group; University of Frankfurt, Frankfurt, Germany; Department of General and Visceral Surgery, University Medical Center, Georg-August-University, Göttingen, Germany; University Erlangen, Erlangen, Germany; Surgical Department of Erlangen University, Erlangen, Germany; Kliniken Maria Hilf, Mönchengladbach, Germany; Division of Biostatistics, University of Zurich, Zurich, Switzerland; Klinik für Tumorbiologie, Freiburg, Germany; Klinikum Oldenburg, Oldenburg, Germany; University of Leipzig, Leipzig, Germany; University of Goettingen, Goettingen, Germany; Klinikum Esslingen, Esslingen, Germany; University of Erlangen, Erlangen, Germany

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Abstract Disclosures


Background: The CAO/ARO/AIO-94 trial established preoperative chemoradiotherapy (CRT), total mesorectal excision (TME) surgery, and adjuvant chemotherapy with 5-FU as standard treatment for locally advanced rectal cancer. The goal of the CAO/ARO/AIO-04 trial was the integrating of more effective systemic treatment. First results of early secondary endpoints have been published (Rödel et al., Lancet Oncol 2012). Here we present the primary endpoint, disease-free survival (DFS) at 3 years. Patients and Methods: Patients with cT3/4 or cN+ rectal cancer were randomised into two arms: 1) preoperative 50.4 Gy plus infusional 5-FU 1 g/m2 days 1-5 and 29-33, followed by TME-surgery and 4 cycles of bolus 5-FU 500 mg/m2 for 5 days), and 2) preoperative 50.4 Gy plus infusional 5-FU (250 mg/m2 days 1-14 and 22-35), oxaliplatin (50 mg/m2 days 1, 8, 22, and 29), followed by TME and 8 cycles of adjuvant oxaliplatin (100 mg/m2 day 1), leucovorin (400 mg/m2 day 1) and infusional 5-FU (2,400 mg/m2 day 1-2). The primary endpoint was DFS at 3 years defined as the interval from randomization to incomplete surgical resection, locoregional or metastatic recurrence or death, whichever occurred first. Results: A total of 637 patients were randomly assigned to arm 1 and 628 to arm 2. After a median follow-up time of 50 months, 198 patients in arm 1 had had a DFS-related event, as compared with 159 patients in arm 2 (HR 0.79, 95% confidence interval 0.64 to 0.98, P=0.03 by the mixed effects Cox model). The rate of DFS at three years was 71.2% (95% confidence interval, 67.6% to 74.9%) in arm 1 and 75.9% (95% confidence interval, 72.4% to 79.5%) in arm 2 (P=0.03 by the exact stratified log-rank test). Grade 3-4 late overall treatment-related toxicity occurred in 23% in arm 1 and 26% in arm 2 (P=0.14). The incidence of grade 3-4 sensory neuropathy in the oxaliplatin containing arm was 7% during treatment, decreasing to 3% at one year of follow-up. Conclusions: Adding oxaliplatin to 5-FU-based neoadjuvant CRT and adjuvant chemotherapy in locally advanced rectal cancer significantly improved DFS. Clinical trial information: NCT00349076.