Byström P, Frödin J-E, Berglund A, Wilking N, Glimelius B
Department of Oncology, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Radiother Oncol. 2004 Feb;70(2):171-5. doi: 10.1016/j.radonc.2004.01.004.
Chemoradiotherapy is increasingly used in the primary management of patients with loco-regionally advanced gastrointestinal (GI) cancer. Oral chemotherapy with uracil and tegafur (UFT) plus leucovorin (LV) may represent a convenient way of delivering protracted infusion of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with radiation and determine the maximum-tolerated dose (MTD) and a recommended dose for further testing.
Patients with inextirpable GI cancer received escalating doses of UFT (starting at 300 mg/m(2)/d with 50 mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). UFT and LV were given 5 days per week concurrently with radiation to 50 Gy (2 Gy/fraction).
Twenty-five patients were treated, and 22 received the planned treatment. Three patients were withdrawn from treatment, two due to disease-progression and one due to toxicity. The MTD of UFT with radiation was 400 mg/m(2)/d with 90 mg/d of LV. Diarrhoea was the main dose limiting toxicity (DLT). Since some toxicity (3/12 DLTs) was seen in the expanded cohort at the level below, but none (0/9 DLT) at the starting level, the recommended dose chosen for further testing is 300-350 mg/m(2)/d depending upon the size of the target volume.
Concomitant chemoradiation with oral UFT plus LV is feasible and well tolerated and should be further investigated since tumour responses were frequently seen.
放化疗在局部晚期胃肠道（GI）癌患者的初始治疗中应用越来越广泛。口服尿嘧啶替加氟（UFT）联合亚叶酸钙（LV）可能是一种方便的持续输注氟尿嘧啶的给药方式。我们的目标是评估UFT联合LV与放疗的安全性，并确定最大耐受剂量（MTD）及进一步试验的推荐剂量。
无法切除的胃肠道癌患者接受递增剂量的UFT（起始剂量为300mg/m²/d，连续队列间每次递增50mg/m²/d）和固定剂量的LV（90mg/d）。UFT和LV每周给药5天，同时进行放疗至50Gy（每次2Gy）。
25例患者接受治疗，22例完成计划治疗。3例患者退出治疗，2例因疾病进展，1例因毒性反应。UFT联合放疗的MTD为400mg/m²/d，LV为90mg/d。腹泻是主要的剂量限制性毒性（DLT）。由于在较低剂量水平的扩大队列中出现了一些毒性反应（3/12例DLT），但起始剂量水平未出现（0/9例DLT），根据靶体积大小，进一步试验选择的推荐剂量为300 - 350mg/m²/d。
口服UFT联合LV同步放化疗是可行的且耐受性良好，鉴于经常观察到肿瘤反应，应进一步研究。
