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

Abstract

BACKGROUND\nNeoadjuvant chemoradiotherapy and total mesorectal excision comprise 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.\n\n\nOBJECTIVE\nTo evaluate the feasibility and efficacy of S-1 and oxaliplatin neoadjuvant chemotherapy together with total mesorectal excision for resectable locally advanced rectal cancer.\n\n\nDESIGN\nThe study was a prospective, single-arm phase II trial.\n\n\nSETTINGS\nThe study was conducted at multiple institutions.\n\n\nPATIENTS\nFifty-eight patients with resectable locally advanced rectal cancer were enrolled.\n\n\nINTERVENTION\nThree cycles of S-1 and oxaliplatin were administered before surgery. S-1 was administered orally at 80 mg/m2/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/m2/day. The duration of one cycle was considered to be 21 days. Total mesorectal excision with bilateral lymph node dissection was carried out after neoadjuvant chemotherapy.\n\n\nMAIN OUTCOME MEASURES\nThe study was designed to detect the feasibility and efficacy of S-1 and oxaliplatin as neoadjuvant chemotherapy.\n\n\nRESULTS\nThe completion rate of three 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 of 52 patients (98.1%). Pathological complete response occurred in 10 patients (19.2%).\n\n\nLIMITATIONS\nThis was a single-arm, nonrandomized phase II study.\n\n\nCONCLUSIONS\nThe 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://links.lww.com/DCR/B555.