title: Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study.
abstract: The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m(2) twice daily.
authors.affiliation: Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan mhosono@med.osaka-cu.ac.jp.
authors.forename: Masako
authors.initials: M
authors.lastname: Hosono
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nagahara
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.affiliation: Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Shimatani
authors.affiliation: Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Department of Radiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Miki
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011183:Postoperative Complications / Q000209:etiology; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil
keywords: bevacizumab; capecitabine; chemoradiotherapy; rectal cancer