Chronicle: Results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (Xelox) versus control
Mené sur 113 patients atteints d'un cancer rectal de stade localement avancé, cet essai de phase III évalue, du point de vue de la survie sans maladie, de la survie globale à 3 ans et de la toxicité, l'intérêt d'une chimiothérapie adjuvante par capécitabine plus oxaliplatine après une chimioradiothérapie néoadjuvante et un traitement chirurgical
Background : In stage III colon cancer oxaliplatin/5FU-based adjuvant chemotherapy (FOLFOX) improves disease-free survival (DFS) and overall survival (OS). In rectal adenocarcinoma following neoadjuvant chemoradiation (CRT), we examined the benefit of postoperative adjuvant capecitabine and oxaliplatin (XELOX) chemotherapy. Methods : Eligible patients were randomly assigned following fluoropyrimidine-based CRT and curative resection to observation or 6 cycles of XELOX. The primary endpoint was DFS; secondary endpoints were acute toxicity and OS. 390 patients were required in each arm, to detect an improvement in 3-year DFS from 40% to 50.5%, with 85% power and two-sided 5% significance level. Results : The study closed prematurely in 2008 because of poor accrual. Only 113 patients were randomly assigned to either observation (n=59) or XELOX (n=54). Compliance was poor, 93% allocated chemotherapy started and 48% completed 6 cycles. Protocolised dose reductions in XELOX were 39%, and levels of G3/G4 toxicity 40%. After a median follow-up of 44.8 months, 16 patients (27%) in the observation arm had relapsed or died compared with 12 patients (22%) in XELOX. The 3-year DFS rate was 78% with XELOX and 71% with observation (hazard ratio [HR] for DFS=0.80; 95% CI: 0.38-1.69; p=0.56). The 3-year OS for XELOX and observation were 89% and 88% respectively (HR for OS=1.18; 95% CI: 0.43-3.26; p=0.75). Conclusions : The observed improvement in DFS for adjuvant XELOX and similar OS were not statistically significant, as expected given the small number of patients and consequent low power. Our findings support the need for trials that test the role of neoadjuvant chemotherapy.
Annals of Oncology 2014