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5 - flourouracil figure 2.8

cytarabine. Fluorouracil is a fluorinated pyrimidine that becomes phosphorylated intracellularly and then binds covalently with thymidylate synthetase, thereby inhibiting its action and interfering with DNA and RNA synthesis (see Fig. 2.8) [8,21]. There is little evidence that fluorouracil has activity against PBT as a single agent or in combination with other drugs. When administered as part of a phase III trial investigating intravenous versus intra-arterial BCNU, fluorouracil did not improve survival in either of the BCNU groups [142]. In a phase II trial of 30 patients with various PBT, Cascino and coworkers administered fluorouracil (370 mg/m2) with leucovorin modulation for five days every five weeks [143]. Only three objective responses were noted, with a median time to progression of 6.7 weeks and an overall median survival of 16.1 weeks. The most frequent toxicities of fluorouracil are myelosuppres-sion, stomatitis, and diarrhea. Rarely, an acute cerebellar syndrome can develop that appears to be correlated with peak plasma concentrations of drug.

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