Purpose: Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin.
Patients and Methods: We randomly assigned patients to receive 5weeks of treatment with radiotherapy 45Gy/25 fractions with concurrent capecitabine 800mg/m2 twice daily 5days per week (Cap 45) or radiotherapy 50Gy/25 fractions with capecitabine 800mg/m2 twice daily 5days per week and oxaliplatin 50mg/m2 once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR).
Results: Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n=299) or Capox 50 (n=299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P<.001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P=.09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P=.008). The rate of positive circumferential rectal margins (between 0 and 2mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P=.02).
Conclusion: The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.