Neoadjuvant mFOLFOXIRI Plus Bevacizumab in Patients With High-Risk Locally Advanced Rectal Cancer

Multimodality treatment that comprises preoperative fluoropyrimidine with concurrent radiotherapy followed by total mesorectal excision (TME) surgery and adjuvant fluoropyrimidine-based chemotherapy is recommended as a standard treatment of patients with stage II/III rectal cancer. However, the main target of radiotherapy is local control but no improvement in disease-free survival (DFS) or overall survival (OS) has been shown with this treatment strategy, which leaves approximately 30% of patients in whom distant metastases will develop. Moreover, the short- and long-term adverse effects of radiotherapy such as chronic pain, faecal incontinence and urogenital/anal dysfunction are associated with poor quality of life. Neadajuvant chemotherpay (NACT) alone has been proposed instead of preoperative chemoradiotherapy (CRT) with the aim of elimination of potential micrometastasis as early as possible while avoiding the adverse effects of radiotherapy, without jeopardizing local control. Evidence from the UK CR07 trial suggests that, without RT, a local recurrence rate of 5% (27/543) can be achieved if a complete mesorectal excision is carried out with a negative CRM. A small single-center phase II pilot trial treated patients with stage II or III rectal cancer with induction FOLFOX/bevacizumab chemotherapy followed by CRT only in those with stable or progressive disease and resection in all patients. All 32 of the participants had an R0 resection, and the 4-year DFS was 84%. Another phase II trial, which included 60 patients with stage II/III rectal cancer, assessed the R0 resection rate after FOLFOX plus either bevacizumab or cetuximab. An R0 resection was achieved in 98.3% of the participants, and the pathologic complete response rate was 16.7%. The phase III FOWARC trial, compared neoadjuvant therapy with and without radiation and found that perioperative mFOLFOX6 alone led to a similar downstaging rate as fluorouracil-radiotherapy, and no significant difference in