Fleming G F, Schilsky R L, Schumm L P, Meyerson A, Hong A M, Vogelzang N J, Ratain M J
Department of Medicine, University of Chicago Medical Center, IL 60637-1470, USA.
Ann Oncol. 2003 Jul;14(7):1142-7. doi: 10.1093/annonc/mdg302.
Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice.
Patients with solid tumors were eligible if they were able to fit into one of three organ dysfunction cohorts: I, creatinine >1.5 but < or =3.0 mg/dl and normal bilirubin; II, bilirubin >1.5 but <5.0 mg/dl with normal creatinine; or III, bilirubin > or =5.0 mg/dl with normal creatinine. 5-FU doses were escalated separately within each of the three cohorts. Leucovorin (LV) dosage was fixed at 500 mg/m(2). 5-FU was given as a 24-h infusion at 1000, 1800 or 2600 mg/m(2), and plasma concentrations were measured every 3 h during the first two infusions for each patient.
Sixty-four patients were treated. Toxicities did not appear to be related to organ dysfunction cohort. A weekly dose of of 5-FU 2600 mg/m(2) produced dose-limiting toxicity (DLT) in six of 20 evaluable patients. These DLTs included grade 3 fatigue (n = 3), grade 2 neutropenia precluding weekly dosing (n = 1), grade 3 thrombocytopenia (n = 1) and grade 3 mental status changes (n = 1). There was no relationship between serum bilirubin or serum creatinine and 5-FU clearance.
Patients with elevated bilirubin may be safely started on a weekly regimen of 5-FU 2600 mg/m(2) with leucovorin 500 mg/m(2) as a 24-h continuous infusion.
肝功能或肾功能不全的患者常接受5-氟尿嘧啶（5-FU）治疗，但鲜有数据证实这种治疗方法的安全性。
实体瘤患者若符合以下三个器官功能不全队列之一即可入选：队列I，肌酐>1.5但≤3.0mg/dl且胆红素正常；队列II，胆红素>1.5但<5.0mg/dl且肌酐正常；或队列III，胆红素≥5.0mg/dl且肌酐正常。5-FU剂量在三个队列中分别递增。亚叶酸钙（LV）剂量固定为500mg/m²。5-FU以1000、1800或2600mg/m²的剂量进行24小时输注，每位患者在前两次输注期间每3小时测量一次血浆浓度。
64例患者接受了治疗。毒性似乎与器官功能不全队列无关。每周剂量为2600mg/m²的5-FU在20例可评估患者中有6例产生了剂量限制性毒性（DLT）。这些DLT包括3级疲劳（n = 3）、2级中性粒细胞减少导致无法每周给药（n = 1）、3级血小板减少（n = 1）和3级精神状态改变（n = 1）。血清胆红素或血清肌酐与5-FU清除率之间无相关性。
胆红素升高的患者可以安全地开始接受每周一次的5-FU 2600mg/m²联合亚叶酸钙500mg/m²的24小时持续输注方案。
