CENTRAL-NERVOUS-SYSTEM TOXICITY OF FLUDARABINE PHOSPHATE

  • 1 October 1986
    • journal article
    • research article
    • Vol. 70  (10) , 1225-1228
Abstract
Fourteen patients developed severe central nervous system (CNS) toxicity after receiving an investigational antitumor agent, fludarabine phosphate (FAMP). The CNS toxicity has the distinctive features of delayed onset and progressive clinical course. Visual deficits were the most common presenting symptom and developed eventually in most cases. Deterioration of mental status and progressive encephalopathy were also observed. The development of clinical CNS toxicity appears dose-related; thirteen of 36 patients (36.1%) who received FAMP at high doses (.gtoreq. 96 mg/m2/day for 5-7 days per course) developed neurotoxicity, while only one of 443 patients (0.2%) show received the drug at low doses (.ltoreq. 125 mg/m2 per course) developed similar toxicity. Although the precise mechanism responsible for this toxicity is yet unknown, progressive demyelination appear to be the responsible of process. Extensive review of the clinical data failed to identify factors which might contribute to the development of CNS toxicity. Patients on trials of FAMP should be meticulously monitored for the possible development of neurotoxicity.

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