Saad E D, Hoff P M
Department of Oncology, Albert Einstein Hospital, Sao Paulo, Brazil.
Oncology (Williston Park). 2001 Jan;15(1 Suppl 2):65-8.
Researchers, primarily in Japan, Europe, and the United States, have evaluated several new fluorinated pyrimidines in recent years. Most of these drugs are orally active prodrugs of fluorouracil (5-FU), and some also contain modulators of its pharmacological properties. S-1 is a rationally developed combination of tegafur, a prodrug of 5-FU; CDHP, an inhibitor of 5-FU catabolism; and potassium oxonate, an inhibitor of 5-FU-induced diarrhea. S-1 underwent phase I and II trials in Japan, where it is now approved for use in the treatment of advanced gastric cancer. Two phase I studies conducted recently in Europe and the United States identified diarrhea as the dose-limiting toxicity of S-1. BOF-A2, which contains a 5-FU prodrug and CNDP, an inhibitor of 5-FU catabolism, demonstrated clinical activity in preliminary studies in Japan. This article summarizes the preclinical and clinical development of S-1 and BOF-A2.
近年来，主要来自日本、欧洲和美国的研究人员对几种新型氟嘧啶进行了评估。这些药物大多是氟尿嘧啶（5-FU）的口服活性前体药物，有些还含有其药理特性调节剂。S-1是替加氟（一种5-FU前体药物）、CDHP（一种5-FU分解代谢抑制剂）和奥索酸钾（一种5-FU诱导腹泻的抑制剂）的合理组合。S-1在日本进行了I期和II期试验，目前已在日本获批用于治疗晚期胃癌。欧洲和美国最近进行的两项I期研究确定腹泻是S-1的剂量限制性毒性。BOF-A2含有一种5-FU前体药物和CNDP（一种5-FU分解代谢抑制剂），在日本的初步研究中显示出临床活性。本文总结了S-1和BOF-A2的临床前和临床开发情况。
