489 Background: The study tested whether preoperative 5x5 Gy and consolidation chemotherapy is more locally efficacious than standard preoperative chemoradiation in “unresectable” cancer (ClinicalTrials.gov NCT00833131). Methods: Patients with fixed cT3 or cT4 rectal cancer without distant metastases were randomized either to 5x5 Gy and 3 courses of FOLFOX4 after one week rest (experimental group) or to 50.4 Gy delivered in 28 fractions given simultaneously with a 5-Fu bolus, leucovorin and oxaliplatin (control group). For the second study part, oxaliplatin was delivered to the two groups at the discretion of the participating centre. Both groups underwent surgery about 12 weeks after starting radiation and about 6 weeks after neoadjuvant treatment. Results: 515 patients were eligible for analysis; 261 in the experimental group and 254 in the control group. Acute toxicity of neoadjuvant treatment was recorded in 74% of patients in the experimental group and in 83% in the control group, p = 0.007; the rate of patients with grade 3+ toxicity was identical in the two groups - 24%. R0 resection rates (primary endpoint) and pathological complete response rates were respectively in the experimental group and in the control group 77% vs. 71% (p = 0.081) and 16% vs. 11.5% (p = 0.19). Median follow-up was 35 months. At 3 years, rates of overall survival, disease-free survival and cumulative incidence of local failure were respectively in the experimental group and in the control 73% vs. 64.5%, p = 0.055; 53% vs. 52%, p = 0.74 and 22% vs. 21%, p = 0.82. Conclusions: The trial showed no difference in local efficacy between preoperative 5x5 Gy with consolidation chemotherapy and standard preoperative chemoradiation. The trend towards improved overall survival, lower toxicity, lower cost and convenience favors 5x5 Gy with consolidation chemotherapy. Clinical trial information: NCT00833131.
Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study