Total neoadjuvant treatment (CAPOX plus radiotherapy) for patients with locally advanced rectal cancer with high risk factors: a phase 2 trial

Abstract

BackgroundStandard neoadjuvant concurrent chemoradiotherapy does not improve overall survival in stage II–III rectal cancer and total neoadjuvant treatment might be a better treatment option for patients with high risk factors. We aimed to evaluate the safety and efficacy of total neoadjuvant treatment (CAPOX [oxaliplatin and capecitabine] and intensity-modulated radiation therapy [IMRT] with volumetric-modulated arc therapy [VMAT]) in patients with rectal cancer with high risk factors. MethodsWe did this phase 2 trial in patients who were diagnosed with stage II–III rectal cancer. We recruited patients with at least one high risk factors: cT4b, cN2, extramural venous invasion positive, involved mesorectal fascia positive, or lateral lymph nodes positive. Three cycles of induction CAPOX were followed by pelvic IMRT with VMAT and two cycles of concurrent CAPOX. Three cycles of consolidation CAPOX were delivered after radiotherapy. Primary endpoints were pathological complete response and R0 resection. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR-OIN-17012284. FindingsFrom June, 2015, to April, 2017, 47 patients were evaluable. One patient (2%) who had acute intestinal obstruction after the first cycle of chemotherapy underwent emergency total mesorectal excision. A total of 29 patients (62%) completed eight cycles of chemotherapy and 46 patients (98%) completed the planned radiotherapy. 17 patients (36%) achieved a pathological complete response or clinical complete response, in which 12 patients (71%) completed eight cycles of chemotherapy. Five patients (11%) refused the operation and selected a watch and wait strategy. R0 resection for patients who underwent total mesorectal excision was 100%. The mean operation time was 207 min (median 195 min, range 120–370 min) and the mean estimated blood loss was 89 mL (median 50 mL, range 10–500 mL). The most common grade 3 or worse adverse events associated with the neoadjuvant administration were leucopenia (10%), diarrhoea (5%), radiation dermatitis (5%), and thrombocytopenia (2%). The most common grade 3 or worse surgery-related complications were pelvic abscesses, anastomotic leakage, and haemorrhage, which were observed in one patient, respectively. InterpretationTotal neoadjuvant treatment is effective and safe for patients with local advanced rectal cancer with high risk factors. Long-term efficacies of total neoadjuvant treatment need to be evaluated. FundingProject of Health and Family Planning Commission of Sichuan Province.