Fluorouracil 5-FU

FU = fluorouracil, CDDP = cisplatin, Mito = mitomycin-C, RT = radiation therapy. 

FU, fluorouracil HD-LV, high-dose leucovorin LD-LV, low-dose leucovorin LEV = Reproduced with permission from Macdonaldd ... 

Fluoropyrknidine derivatives are of tremendous importance in cancer chemotherapy, eg, 5-fluorouracil [51-21-8] (5-FU). The original 5-fluorouracil process featured a multistep low yield route based on ethyl fluoroacetate (451). Direct fluorination (fluorine) of uracil [66-22-8] gives high yields of 5-FU (452—455). This process has now been commercialized. 

Tetrafluoropyrimidine was converted to the antiaeoplastic 5-fluorouracil (5-FU) by a novel process based on the sequence partial exchange chlorination (61% yield), selective hydrogenolysis ia triethylamine (71% yield) and hydrolysis (85—93% yield) (464). 

A landmark scientific breakthrough resulted from the synthesis and metabohc studies of 5-fluorouracil (5) (fl ura or 5-FU), 5-fluoroorotic acid ( f) (fl oro), and 5-fluorocytosine (7) (fl cyt) by Heideiberger and co-workers [2] Several excellent recent reviews are available on this important field [9, 23, 24, 25, 26 ]. 

Interest contmues in prodrugs of 5-fluorouracil (5-FU) Doxifluridine (8) was recently mtroduced and appears to be more potent and less toxic than 5 FU [10 Flutamide (9) and nilutamide (/O) are both available for the treatment of prostatic cancer [//, 12]... 

Fluorouracil (5-fluorouracil, 5-FU, Fig. 5) represents an early example of rational drag design in that it originated from the observation that tumor cells, especially from gut, incorporate radiolabeled uracil more efficiently into DNA than normal cells. 5-FU is a fluorinated pyrimidine analog that must be activated metabolically. In the cells 5-FU is converted to 5-fluoro-2>deoxyuridine-monophosphate (FdUMP). This metabolite inhibits thymidilate synthase which catalyses the conversion of uridylate (dUMP) to thymidilate (dTMP) whereby methylenetetrahydrofo-late plays the role of the carbon-donating cofactor. The reduced folate cofactor occupies an allosteric site of... 

One commonly used agent is the antimetabolite 5-fluorouracil (5-FU), which is frequently used as an adjuvant therapy in conjunction with surgical excision in the treatment of solid tumors. p53 can directly trigger apoptosis in cells exposed to 5-FU in vitro [1]. In addition, there is a substantial amount of clinical... 

Since the theory and medical applications of collagen sponge were described by Chvapil et al. (52-54), they have been used to deliver steroid hormones (55), the anticancer drugs trans-retinoic acid (TRA) (56,57), and 5-fluorouracil (5-FU) (58), and antibiotics (59). 

Fluorouracil-based chemotherapy is the standard of care for the adjuvant treatment of colorectal cancer either as a single agent or, more commonly, in combination with other agents. 5-Fluorouracil (5-FU) alone results in a small improvement in survival that can vary based on the method of 5-FU administration. Studies suggest that protracted or continuous intravenous (IV) 5-FU infusion treatment schedules are more effective than bolus therapy.20... 

Fluorouracil (5-FU) acts as a false pyrimidine, inhibiting the formation of the DNA base thymidine.26,35 The main mechanism by which it accomplishes this is by inhibiting the enzyme thymidylate synthase, the rate-limiting step in thymidine formation. 5-FU first must be metabolized to its active metabolite (F-dUMP). Additionally, metabolites of 5-FU may incorporate into RNA, inhibiting its synthesis. 

Gamelin E, Boisdron-Celle M, Guer-in-Meyer V et al. Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer a potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J Clin Oncol 1999 17 1105-1110. 

Fluorouracil (5-FU)/ leucovorin (Mayo)- metastatic 5-FU 425 mg/M2 Leucovorin 20 mg/M2 REF Buroker et al. J Clin Oncol 1994 Repeat every 28-35 days IV bolus IV bolus 12 14-20 days 1 -5 days 1 -5... 

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