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Investigational new drugs

Fludarabine phosphate. A new anticancer drug with significant activity in patients with chronic lymphocytic leukemia and in patients with lymphoma.


PMID 7532163

Abstract

Fludarabine phosphate is a purine antimetabolite approved for use in the management of patients with chronic lymphocytic leukemia. Fludarabine works primarily by inhibiting DNA synthesis. The compound also possesses lymphocytotoxic activity with preferential activity toward T-lymphocytes. Initial preclinical studies demonstrated antitumor activity with fludarabine against L1210 murine leukemia. In phase I studies, myelosuppression was identified as the dose-limiting toxicity in patients with solid tumors and fatal neurotoxicity as the dose-limiting toxicity in adult patients with acute hematologic malignancies. The recommended dose and schedule was determined to be 18-25 mg/m2/d for five days, repeated every 28 days. Unlike preclinical studies, phase II trials showed a lack of significant effect when fludarabine was given to patients with solid tumors. However, phase II investigations have confirmed the efficacy of fludarabine in lymphoid malignancies, including non-Hodgkin's lymphoma, mycosis fungoides, prolymphocytic leukemia, and chronic lymphocytic leukemia. The place of fludarabine in the management of leukemias in children is under investigation. Early results indicate an unusual degree of antitumor activity when the agent is used in combination chemotherapy for patients with refractory disease. Fludarabine is an effective antitumor agent in the management of lymphoid malignancies. Studies are ongoing to more completely define the role of fludarabine in these malignancies as well as in the pediatric leukemias. Additional studies evaluating the activity of fludarabine as an immunomodulator are warranted, due to the lymphocytotoxic properties associated with this agent.