D Azria1, J Doyen2, M Jarlier3, I Martel-Lafay4, C Hennequin5, P Etienne6, V Vendrely7, E François8, G de La Roche9, O Bouché10, X Mirabel11, B Denis12, L Mineur13, J Berdah14, M Mahé15, Y Bécouarn16, O Dupuis17, G Lledo18, J Seitz19, L Bedenne20, S Gourgou-Bourgade3, B Juzyna21, T Conroy22, J Gérard23. 1. Department of Radiation oncology, Montpellier Cancer Institute, Montpellier. 2. Department of Radiation oncology, Antoine-Lacassagne Center, Nice;; University of Côte d'Azur, Nice;. Electronic address: jerome.doyen@nice.unicancer.fr. 3. Biometrics Unit, Montpellier Cancer Institute, Montpellier. 4. Department of Radiation Oncology, Léon-Bérard Center, Lyon. 5. Department of Radiation Oncology, Saint-Louis Hospital, Paris. 6. Department of Radiation Oncology, Armorican Center of Radiotherapy and Radiology, Plérin. 7. Department of Radiation Oncology, Teaching Hospital CHU of Bordeaux, Bordeaux. 8. University of Côte d'Azur, Nice;; Department of Medical Oncology, Antoine-Lacassagne Center, Nice. 9. Department of Medical Oncology, Oncology Institute of Loire, Saint Priest en Jarez. 10. Department of Medical Oncology, Teaching Hospital CHU of Reims, Reims. 11. Department of Radiation Oncology, Oscar-Lambret Center, Lille. 12. Department of Medical Oncology, Teaching Hospital CHU Louis Pasteur, Colmar. 13. Department of Radiation Oncology, Sainte-Catherine Institute, Avignon. 14. Sainte-Marguerite Private Hospital, Toulon-Hyères. 15. Department of Radiation Oncology, West Oncology Institute, Saint-Herblain. 16. Department of Medical Oncology, Institut Bergonié, Bordeaux. 17. Department of Medical Oncology, Jean Bernard Center, Le Mans. 18. Department of Medical Oncology, Jean Mermoz Private Hospital, Lyon. 19. Department of Medical Oncology, Teaching Hospital CHU La Timone, Marseille. 20. Department of Medical Oncology, Teaching Hospital CHU of Dijon, Dijon. 21. Unicancer, Paris. 22. Department of Medical Oncology, Oncology Institute of Lorraine, Vandoeuvre-les-Nancy, France. 23. Department of Radiation oncology, Antoine-Lacassagne Center, Nice;; University of Côte d'Azur, Nice.
Abstract
BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.
BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.
Authors: Felix J Hüttner; Pascal Probst; Eva Kalkum; Matthes Hackbusch; Katrin Jensen; Alexis Ulrich; Jürgen Debus; Dirk Jäger; Markus K Diener Journal: J Natl Cancer Inst Date: 2019-09-01 Impact factor: 13.506