Postoperative XELOX therapy for patients with curatively resected high-risk stage II and stage III rectal cancer without preoperative chemoradiation: a prospective, multicenter, open-label, single-arm phase II study

Tsunekazu Mizushima,Masataka Ikeda,Masaki Mori,Taroh Satoh,Takeshi Kato,Junichi Nishimura,Atsuyo Ikeda,Yuichiro Doki,Chu Matsuda,Taishi Hata

doi:10.1186/s12885-019-6122-2

Abstract

BackgroundPreoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer.MethodsWe performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS).ResultsBetween August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29–77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of ‘0’ and 14 had scores of ‘1’. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8–78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7).ConclusionsPostoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects.Trial registrationThis clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.

Highlights

Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, in Western countries
In a study of postoperative adjuvant chemotherapy after preoperative chemoradiation, Hong et al found that disease-free survival (DFS) for patients treated with postoperative FOLFOX after preoperative 5FU-based chemoradiotherapy and total mesorectal excision (TME) was 71.6%, which was significantly better than the 62.9% 3-year DFS rate for patients treated with 5-FU/l-leucovorin [7]
Adjuvant radiotherapy has not been widely used for a long time in Japan, and TME with lateral lymph node dissection or TME with 5-FU based adjuvant chemotherapy has been the standard treatment [8]

Summary

Introduction

Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, in Western countries. It reduced the local recurrence, it could not necessarily improve overall survival. Chemotherapy and radiotherapy are both used as adjuvant therapies before and after the curative resection of advanced rectal cancer, and aim to prevent recurrence and extend survival by eliminating micrometastases. Studies of the efficacy of 5-fluorouracil (5-FU)-based postoperative adjuvant chemotherapy have been performed since the 1980s; based on the results of clinical trials such as the MOSAIC, NSASBPC-04, and NO16968 trials, the current standard treatment involves either combination 5-FU/ oxaliplatin-based therapies (5-FU, leucovorin, and oxaliplatin [FOLFOX] or [FLOX]) or alternatively oral fluoropyrimidine capecitabine and oxaliplatin (XELOX) [1,2,3]. We conducted a clinical trial to evaluate the efficacy of surgery and postoperative adjuvant XELOX therapy without preoperative chemoradiation for treating rectal cancer

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