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.

To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer. Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment. 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II. The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies.