Hohneker J A
Oncology Clinical Development, Glaxo Wellcome Inc., Research Triangle Park, North Carolina, USA.
Oncology (Williston Park). 1998 Oct;12(10 Suppl 7):52-6.
Eniluracil is a potent inactivator of dihydropyrimidine dehydrogenase (DPD), which is the first enzyme in the degradative pathway of systemically administered 5-fluorouracil (5-FU). Two completely oral regimens of eniluracil plus 5-FU are being evaluated in clinical trials: (1) a chronic schedule with both agents administered BID in a 10:1 ratio for 28 days of a 5-week course, and (2) a 5-day schedule of eniluracil once daily on days 1 through 7 and 5-FU once daily on days 2 through 6. The clinical development of eniluracil is being pursued in several tumor types, including colorectal cancer, breast cancer, and pancreatic cancer. Response rates achieved in a phase II study of the chronic schedule of oral eniluracil/5-FU in patients with colorectal cancer compare favorably with those obtained in trials of intravenous 5-FU and leucovorin, while results from other trials are awaited. Safety analysis for the 28-day schedule has revealed a low incidence of severe toxicities, particularly as compared with standard 5-FU regimens.
依鲁替康是二氢嘧啶脱氢酶（DPD）的强效灭活剂，DPD是全身给药的5-氟尿嘧啶（5-FU）降解途径中的首个酶。依鲁替康联合5-FU的两种完全口服方案正在临床试验中进行评估：（1）一种长期方案，两种药物以10:1的比例每日两次给药，为期5周疗程中的28天；（2）一种为期5天的方案，依鲁替康在第1至7天每日一次给药，5-FU在第2至6天每日一次给药。依鲁替康正在多种肿瘤类型中进行临床开发，包括结直肠癌、乳腺癌和胰腺癌。在一项针对结直肠癌患者的口服依鲁替康/5-FU长期方案的II期研究中所取得的缓解率，与静脉注射5-FU和亚叶酸的试验结果相比具有优势，同时其他试验的结果有待观察。对28天方案的安全性分析显示严重毒性的发生率较低，特别是与标准5-FU方案相比。
