Infusional 5-FU: historical evolution, rationale, and clinical experience.
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.
Lokich
J
J
Cancer Center of Boston, Massachusetts, USA.
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000266:history; D017326:Clinical Trials, Phase III as Topic; D005472:Fluorouracil / Q000008:administration & dosage* / Q000266:history; D049673:History, 20th Century; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil