Long-course oxaliplatin based preoperative chemoradiation vs. 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomised phase III study
Mené sur 515 patients atteints d'un cancer rectal de stade cT3 ou cT4 (durée médiane de suivi : 35 mois), cet essai randomisé de phase III compare l'efficacité, du point de vue du taux de résection R0, du taux de réponse pathologique complète et des taux de survie, et la toxicité de deux protocoles pré-opératoires, l'un comportant une chimioradiothérapie de longue durée à base d'oxaliplatine, l'autre une radiothérapie en combinaison avec une chimiothérapie de consolidation de type FOLFOX4
Background : Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. Patients and methods : Patients with fixed cT3 or cT4 cancer were randomised either to 5x5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5-Fu 325 mg/m2/day and leucovorin 20 mg/m2/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m2 once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. Results : Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, p=0.006; any toxicity being respectively 75% vs. 83%, grade III-IV 23% vs. 21% and toxic deaths 1% vs. 3%. R0 resection rates (primary endpoint) and pathological complete response rates in groups A and B were respectively 77% vs. 71%, p=0.07 and 16% vs. 12%, p=0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were respectively 73% vs. 65%, p=0.046 and 53% vs. 52%, p=0.85, together with the cumulative incidence of local failure and distant metastases being respectively 22% vs. 21%, p=0.82 and 30% vs. 27%, p=0.26. Postoperative and late complications rates in group A and group B were respectively 29% vs. 25%, p=0.18 and 20% vs. 22%, p=0.54. Conclusions : No differences were observed in local efficacy between 5x5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5x5 Gy schedule with consolidation chemotherapy.
Annals of Oncology 2016