Lokich J
Cancer Center of Boston, Massachusetts, USA.
Oncology (Williston Park). 1998 Oct;12(10 Suppl 7):19-22.
The cycle-specific schedule-dependent antimetabolite 5-fluorouracil (5-FU) has been in clinical use for 40 years and has evolved as an important agent in the treatment of a large spectrum of tumors, including all gastrointestinal cancers, breast cancer, head and neck cancer, and bladder cancer. Over these 4 decades, there has been an increased understanding of the optimal method and schedule of administration of 5-FU. Furthermore, the concept of pharmacomodulation and biochemical modulation of 5-FU to increase therapeutic efficacy has emerged as a new strategy in cancer chemotherapy. The specific mechanism by which 5-FU induces lethal injury may vary depending on the administration schedule or the type of biochemical modulation applied. The optimal infusion duration and dose intensity of 5-FU continues to be debated as does the question of the need for biochemical modulation when using infusional schedules. Infusional administration of 5-FU has become the gold standard in the treatment of head and neck cancer, esophageal cancer, gastric cancer (in Great Britain), and rectal and anal cancer. The recent availability of oral formulations for 5-FU in conjunction with the capability of manipulating the metabolism of 5-FU, particularly with dihydropyrimidine dehydrogenase (DPD) inhibitors, may provide a substantial incremental improvement in these therapies by eliminating the need for parenteral administration and the use of ambulatory infusion pumps.
周期特异性的、依赖给药方案的抗代谢药物5-氟尿嘧啶（5-FU）已在临床使用40年，并且已发展成为治疗多种肿瘤的重要药物，这些肿瘤包括所有胃肠道癌症、乳腺癌、头颈癌和膀胱癌。在这40年里，人们对5-FU的最佳给药方法和方案有了更多的了解。此外，对5-FU进行药物调节和生化调节以提高治疗效果的概念已成为癌症化疗中的一种新策略。5-FU诱导致命损伤的具体机制可能因给药方案或所应用的生化调节类型而异。5-FU的最佳输注持续时间和剂量强度仍在争论中，使用输注方案时是否需要生化调节的问题也是如此。5-FU的输注给药已成为头颈癌、食管癌、胃癌（在英国）以及直肠癌和肛管癌治疗的金标准。5-FU口服制剂的近期问世，以及操纵5-FU代谢的能力，特别是与二氢嘧啶脱氢酶（DPD）抑制剂联合使用时，可能通过消除肠外给药的需求和使用门诊输注泵，在这些治疗中带来显著的进一步改善。
