Schiebe Martina E, Reese Thomas, Wenz Frederik, Schmidberger Heinz, Engenhart-Cabillic Rita, Dunst Jürgen, Hess Clemens F, Hoffmann Wolfgang
Department of Radio-Oncology and Radiotherapy, Klinikum Braunschweig, 38114 Braunschweig, Germany.
Anticancer Drugs. 2002 Nov;13(10):1005-9. doi: 10.1097/00001813-200211000-00004.
Continuous 5-fluorouracil (5-FU) infusion during radiation therapy is superior to the application of bolus 5-FU schedules. As an oral therapy, that provides prolonged fluoropyrimidine exposure, uracil and Tegafur (UFT) plus leucovorin (LV) has shown favorable activity with only moderate toxicity in colorectal cancer. The present study was designed to evaluate the safety of UFT+LV combined with pelvic radiation to determine the maximum-tolerated dose (MTD) in recurrent rectal cancer. Patients with recurrent rectal cancer received escalating doses of UFT (starting at 250 mg/m /day with 50 mg/m /day increments between consecutive cohorts) and fixed doses of LV (90 mg). The UFT+LV combination was given 5 days per week simultaneously to a 5-week course of irradiation up to a total dose of 50.4 Gy, 1.8 Gy daily fractions followed by a boost of 5.4 or 9.0 Gy to the gross tumor volume. Nineteen patients were treated and 14 received the full chemotherapy with delivery of all planned radiotherapy. The MTD of UFT was 400 mg/m /day due to the occurrence of dose-limiting diarrhea and emesis. Toxicities were mild and manageable on the lower dose levels. Treatment was feasible mainly on an outpatient base. We conclude that combined chemoradiation with oral UFT+LV is feasible and well tolerated for recurrent rectal cancer patients undergoing pelvic radiation. The safety profile appears comparable to that of i.v. dosing without requiring any i.v. port systems. The recommended doses for further phase II chemoradiation trials are 350 mg/m /day UFT+90 mg LV.
在放射治疗期间持续输注5-氟尿嘧啶（5-FU）优于推注5-FU方案。作为一种口服疗法，尿嘧啶替加氟（UFT）加亚叶酸（LV）可延长氟嘧啶暴露时间，在结直肠癌中显示出良好的活性且毒性仅为中度。本研究旨在评估UFT+LV联合盆腔放疗的安全性，以确定复发性直肠癌的最大耐受剂量（MTD）。复发性直肠癌患者接受递增剂量的UFT（起始剂量为250mg/m²/天，连续队列之间每次递增50mg/m²/天）和固定剂量的LV（90mg）。UFT+LV组合每周给药5天，同时进行为期5周的放疗，总剂量达50.4Gy，每日分次剂量为1.8Gy，随后对大体肿瘤体积追加5.4或9.0Gy。19例患者接受了治疗，14例接受了全部计划放疗的完整化疗。由于出现剂量限制性腹泻和呕吐，UFT的MTD为400mg/m²/天。在较低剂量水平时毒性轻微且可控。治疗主要在门诊进行，可行。我们得出结论，对于接受盆腔放疗的复发性直肠癌患者，口服UFT+LV联合放化疗是可行的且耐受性良好。安全性与静脉给药相当，且无需任何静脉置管系统。进一步II期放化疗试验的推荐剂量为350mg/m²/天UFT+90mg LV。
