Fludarabine: a review.
The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.
Hood
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MA
University of Maryland Cancer Center, Baltimore 21201.
Finley
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RS
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D009369:Neoplasms / Q000145:classification / Q000188:drug therapy; D012074:Remission Induction; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine