Phase I trial of neoadjuvant preoperative chemotherapy with S-1, oxaliplatin, and bevacizumab plus radiation in patients with locally advanced rectal cancer

This phase I study was performed to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicities (DLTs) of oxaliplatin combined with preoperative chemoradiotherapy with S-1, oxaliplatin, and bevacizumab in locally advanced rectal cancer. Eligible patients had a newly diagnosed clinical stage T1-4 N0-3 M0 rectal adenocarcinoma within 12 cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2 Gy daily fractions, 5 days/week, total dose 40 Gy) with concurrent S-1 (80 mg/m(2)/day orally, days 1-5, 8-12, 15-19, and 22-26), bevacizumab (90 min continuous intravenous infusion at 5 mg/kg, days 1 and 15), and oxaliplatin (120 min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40 mg/m(2)/day) was gradually increased to determine the MTD and RD. Surgery was performed 6 weeks after completion of preoperative chemoradiotherapy. 11 patients were enrolled. The MTD of oxaliplatin was considered to be 60 mg/m(2), because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50 mg/m(2). Of the patients who received oxaliplatin at a parts per thousand currency sign RD, 5 (83.3 %) had a clinical response [four pathological responses and one pathological complete response (Grade 3)]. With this new regimen, the MTD of oxaliplatin was 60 mg/m(2), and the RD for phase II studies was 50 mg/m(2). This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study.