Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer

Ann Oncol. 2017 Oct 1;28(10):2436-2442. doi: 10.1093/annonc/mdx351.

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.

Keywords: chemoradiotherapy; intermediate risk; neoadjuvant; oxaliplatin; rectal cancer.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects
  • Capecitabine / therapeutic use*
  • Chemoradiotherapy, Adjuvant / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Survival Rate

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Capecitabine

Associated data

  • ClinicalTrials.gov/NCT00227747