Acute Toxicities Comparison Of Postoperative Chemoradiation Therapy With Capecitabine And Oxaliplatin Versus Capecitabine Alone For Pathological Stage Ii And Iii Rectal Cancer: A Randomized Multicenter Phase 3 Trial

To present acute toxicities comparison of a trial of concurrent capecitabine and radiation therapy with or without oxaliplatin as adjuvant treatment for pathological stage II and III rectal cancer. Patients were randomized to either radiation therapy (45–50.4 Gy/25–28 fractions) with concurrent 1600 mg/m2 capecitabine on days 1–14 and 22–35 (Cap-RT group) or with 1300 mg/m2 capecitabine on days 1–14 and 22–35 and 60 mg/m2oxaliplatin on weeks 1, 2, 4, and 5 (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). To demonstrated 10% improvement for 3-year DFS (from 65% in the Cap-RT group to 75% in the Capox-RT group), a sample size of 570 patients was required. This study has been registered with ClinicalTrials.gov, number NCT00714077. From January, 2008, to December, 2015, 589 eligible patients were enrolled from 8 centers in China. Two hundred ninety-six patients were randomized to the Capox-RT group and 293 to the Cap-RT group. Fewer patients in the Capox-RT group completed radiation therapy (79.4% vs 87.4%, P = 0.009) and concurrent chemotherapy (77.7% vs 92.5%, P = 0.000) on schedule compared with those in Cap-RT group. The global acute toxicities rate was 98.0% in the Capox-RT group and 96.2% in the Cap-RT group (P = 0.211). However, the Capox-RT group showed a higher severe acute toxicities rate (36.1% vs 27.6%, P = 0.027) which mainly was sever GI acute toxicities rate (30.1% vs 21.8%, P = 0.023). The severe hematological toxicities (3.0% vs. 3.1%, P = 0.982) and radiation induced dermatitis (3.0% vs 5.1%, P = 0.202) were comparable. Limited but more acute neurotoxicity was observed in the Capox-RT group than in the Cap-RT group (11.1% vs 2.0%, P = 0.000), no severe acute neurotoxicity was found. This phase III trial showed that acute toxicities of postoperative concurrent chemoradiation for locally advanced rectal cancer were high in both Capox-RT group and Cap-RT group. Oxaliplatin inclusion in the capecitabine-based postoperative regimen increased acute toxicities, especially GI and neurotoxicity toxicities. Longer follow-up is needed to assess survival outcomes.