Rödel Claus, Grabenbauer Gerhard G, Papadopoulos Thomas, Hohenberger Werner, Schmoll Hans-Joachim, Sauer Rolf
Department of Radiotherapy, University of Erlangen, Universitätsstrasse 27, 91054 Erlangen, Germany.
J Clin Oncol. 2003 Aug 15;21(16):3098-104. doi: 10.1200/JCO.2003.02.505.
The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer.
Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors.
Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors < or = 2 cm from the dentate line had sphincter-saving surgery.
Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.
本研究旨在确定术前放疗（RT）联合卡培他滨和奥沙利铂（XELOX-RT）治疗直肠癌患者的可行性和疗效。
32例局部晚期（T3/T4）或低位直肠癌患者接受术前放疗（总剂量50.4 Gy）。卡培他滨在第1至14天和第22至35天以825 mg/m²每日两次的剂量同时给药，奥沙利铂在第1、8、22和29天以50 mg/m²开始给药，计划逐步递增10 mg/m²。II期研究的终点包括降期、组织病理学肿瘤退缩、T4期疾病的可切除性以及低位肿瘤患者的括约肌保留情况。
在6例接受60 mg/m²奥沙利铂治疗的患者中，有2例观察到剂量限制性3级胃肠道毒性。因此，50 mg/m²是II期研究的推荐剂量。在此剂量水平观察到的毒性一般较轻，仅有2例短暂的3级腹泻。骨髓抑制主要为白细胞减少，19%的患者为2级。31例接受手术治疗的患者中有17例（55%）实现了T分期降期，68%的患者淋巴结阴性。19%的切除标本中发现病理完全缓解。79%的T4期疾病患者能够进行切缘阴性的根治性手术，36%距齿状线<或=2 cm的肿瘤患者接受了保留括约肌的手术。
术前XELOX-RT是一种可行且耐受性良好的治疗方法。建议将该方案用于III期评估，比较基于氟尿嘧啶的标准疗法与XELOX化放疗。
