Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomised phase III trial
Mené sur 437 patients atteints d'un adénocarcinome du rectum de stade II ou III (durée médiane de suivi : 5 ans), cet essai multicentrique de phase III évalue, du point de vue de la survie sans maladie, des taux de récidive et de la survie globale à 5 ans, l'efficacité d'une chimiothérapie adjuvante par 5-fluorouracile-leucovorine après un traitement comportant une chimioradiothérapie ou une radiothérapie suivie d'une exérèse mésorectale
Background : The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomised phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision. Patients and Methods : The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and total mesorectal excision. Radiotherapy consisted of 5x5 Gy. Chemoradiotherapy consisted of 25x1.8-2 Gy combined with 5-FU based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR), or eight courses capecitabine (SCRIPT). Randomisation was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end-point was overall survival. Results : Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n=221) or adjuvant chemotherapy (n=216). After a median follow-up of 5.0 years, five-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group (HR 0.93, 95% CI 0.62-1.39; p=0.73). The hazard ratio for disease-free survival was 0.80 (95% CI 0.60-1.07; p=0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (p=0.39). Conclusion : The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and total mesorectal excision on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.