A Prospective Multicenter Phase II Study on the Feasibility and Efficacy of S-1 and Oxaliplatin Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer

BACKGROUND: Neoadjuvant chemoradiotherapy and total mesorectal excision compose the standard of care for rectal cancer in multiple guidelines. However, neoadjuvant chemoradiotherapy has not exhibited clear survival benefits but rather has led to an increase in adverse events. Conversely, neoadjuvant chemotherapy is expected to prevent adverse events caused by radiation, yet this treatment is still controversial. OBJECTIVE: The purpose of this study was to evaluate the feasibility and efficacy of S-1 and oxaliplatin neoadjuvant chemotherapy together with total mesorectal excision for resectable locally advanced rectal cancer. DESIGN: The study was a prospective, single-arm phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Fifty-eight patients with resectable locally advanced rectal cancer were enrolled. INTERVENTION: Three cycles of S-1 and oxaliplatin were administered before surgery. S-1 was administered orally at 80 mg/m(2) per day for 14 consecutive days, followed by a 7-day resting period. Oxaliplatin was given intravenously on the first day at a dose of 130 mg/m(2) per day. The duration of 1 cycle was considered to be 21 days. Total mesorectal excision with bilateral lymph node dissection was carried out after neoadjuvant chemotherapy. MAIN OUTCOME MEASURES: The study was designed to detect the feasibility and efficacy of S-1 and oxaliplatin as neoadjuvant chemotherapy. RESULTS: The completion rate of 3 courses of S-1 and oxaliplatin as neoadjuvant chemotherapy was 94.8% (55/58). The reasons for discontinuation were thrombocytopenia (3.4%) and liver injury (1.7%). The most common severe (grade >= 3) adverse effect of neoadjuvant chemotherapy was thrombocytopenia (3.4%). There were no severe adverse clinical symptoms. Consequently, R0 resection was achieved in 51 (98.1%) of 52 patients. Pathologic complete response occurred in 10 patients (19.2%). LIMITATIONS: This was a single-arm, nonrandomized phase II study. CONCLUSIONS: The combination of S-1 and oxaliplatin neoadjuvant chemotherapy and total mesorectal excision is a feasible and promising treatment option for resectable locally advanced rectal cancer. See Video Abstract at http://linksiww.com/DCR/B555.