Safety of the total neo-adjuvant therapy in rectal cancer treatment. Preliminary results of the randomized trial

Abstract

AIM: assess tolerability and safety of total neoadjuvant therapy (TNT) with three consolidation courses of XELOX for patients with rectal carcinoma.PATIENTS AND METHODS: patients with histologically proven rectal carcinoma were randomly assigned in two groups: in the TNT group after the neoadjuvant CRT 50–54 Gy with capecitabine 3 consolidation courses of XELOX were done, in the CTR group — conventional neoadjuvant CRT 50–54 Gy with capecitabine. The RTOG scale was used to assessed radial reactions, and the NCI-CTC v5.0 scale was used to evaluate toxicity. For selected patients with a complete clinical response «watch and wait» approach was used. Postoperative complications were graded according with the Clavien-Dindo scale. The primary endpoint of study was the complete response rate (clinical and pathomorphological). Secondary endpoints of study: frequency and structure of intraoperative and postoperative complications, the rate of grade 3–4 toxicity of radiotherapy and chemotherapy, R0-resection rates. The study was registered on the ClinicalTrials.gov (NCT04747951).RESULTS: between October 2020 and March 2022, 145 patients were enrolled in the randomized study: 72 patients in the TNT group and 73 patients in the CRT group. The full course of neoadjuvant treatment was completed in 90% patients in the TNT group, comparing with 96% in the CRT group (p = 0.65). The total rate of severe adverse effects of radiation therapy was 59% in the TNT group, comparing with 67% in the CRT group (p = 0.48), with 3–4 grade by RTOG scale were observed only in two cases in the CRT group. During chemotherapy severe adverse effects were observed in 54% in the TNT group comparing with 19% in the CRT group (p < 0.001). Grade 3–4 toxicity was 3% in the TNT group comparing with 2% in the CRT group. The rate of intra- and postoperative complications did not differ between two groups.CONCLUSION: TNT is a safe alternative to conventional CRT.