caa a22 4500 605491046 CHVBK 20210128100508.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10147-014-0733-z doi (NATIONALLICENCE)springer-10.1007/s10147-014-0733-z Phase I trial of neoadjuvant preoperative chemotherapy with S-1, oxaliplatin, and bevacizumab plus radiation in patients with locally advanced rectal cancer [Elektronische Daten] [Hirohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Kozo Yoshikawa, Jun Higashigima, Motoya Chikakio, Hideya Kashihara, Chie Takasu, Noriko Matsumoto, Shozo Eto] Background: 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. Methods: Eligible patients had a newly diagnosed clinical stage T1-4 N0-3 M0 rectal adenocarcinoma within 12cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2Gy daily fractions, 5days/week, total dose 40Gy) with concurrent S-1 (80mg/m2/day orally, days 1-5, 8-12, 15-19, and 22-26), bevacizumab (90min continuous intravenous infusion at 5mg/kg, days 1 and 15), and oxaliplatin (120min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40mg/m2/day) was gradually increased to determine the MTD and RD. Surgery was performed 6weeks after completion of preoperative chemoradiotherapy. Results: 11 patients were enrolled. The MTD of oxaliplatin was considered to be 60mg/m2, because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50mg/m2. Of the patients who received oxaliplatin at≤RD, 5 (83.3%) had a clinical response [four pathological responses and one pathological complete response (Grade 3)]. Conclusions: With this new regimen, the MTD of oxaliplatin was 60mg/m2, and the RD for phase II studies was 50mg/m2. This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study. Japan Society of Clinical Oncology, 2014 Bevacizumab nationallicence Neoadjuvant chemoradiotherapy nationallicence Oxaliplatin nationallicence Phase I study nationallicence Rectal cancer nationallicence S-1 nationallicence Sato Hirohiko Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Shimada Mitsuo Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Kurita Nobuhiro Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Iwata Takashi Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Yoshikawa Kozo Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Higashigima Jun Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Chikakio Motoya Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Kashihara Hideya Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Takasu Chie Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Matsumoto Noriko Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut Eto Shozo Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut International Journal of Clinical Oncology Springer Japan 20/3(2015-06-01), 543-548 1341-9625 20:3<543 2015 20 10147 https://doi.org/10.1007/s10147-014-0733-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-014-0733-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sato Hirohiko Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Shimada Mitsuo Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Kurita Nobuhiro Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Iwata Takashi Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Yoshikawa Kozo Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Higashigima Jun Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Chikakio Motoya Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Kashihara Hideya Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Takasu Chie Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Matsumoto Noriko Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 700 1- Eto Shozo Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/3(2015-06-01), 543-548 1341-9625 20:3<543 2015 20 10147