Pharmacotherapy Update: Fludarabine in the Treatment of Non-Hodgkin's Lymphoma

Fludarabine, a purine nucleoside analogue, is considered as the most active drug in chronic lymphocytic leukemia. This review summarizes current knowledge concerning the mechanism of action, pharmacological properties, clinical activ- ity and toxicity of fl udarabine in the treatment of non-Hodgkin's lymphoma. A literature search on fl udarabine for lymphomas was undertaken using MEDLINE databases. Clinical data shows that fl udarabine alone and as a component of combination chemotherapy is effective in patients with various types of non-Hodgkin's lymphoma, particularly in follicular lymphoma. The most commonly used combinations are with cyclophosphamide and/or mitoxantrone. Fludarabine-based regimens are highly active in both previously untreated and relapsed indolent lymphomas. The results of the chemotherapy are consider- ably improved with the addition of rituximab. Fludarabine is generally well tolerated. Myelosuppression and infections, including opportunistic varieties, are the most frequent adverse effects. Indications for fl udarabine and treatment regimens for lymphoma patients are discussed. Introduction success of the pyrimidine nucleoside cytarabine in the treatment of acute leukemias prompted development of new purine nucleoside analogues. 1 The most promising agents in this group are deoxy- coformycin (pentostatin), fl udarabine phosphate and 2-chloro-2'-deoxyadenosine (2CdA) that cause suppression of DNA synthesis and repair in the tumor cells by distinct enzymatic processes. Fludarabine, synthesized by Montgomery and Hewson in 1969, 2 was fi rst studied in acute leukemia using high doses (150 mg/m 2 /d for 5-7 days) and found to be excessively toxic to the nervous system. 3 Subsequently fl udarabine at lower doses revealed impressive activity in the treatment of indolent lymphoproliferative diseases. 4-6 Currently fl udarabine is considered as the most active drug in chronic lymphocytic leukemia (CLL) inducing complete remission (CR) in about 30% of previously untreated patients, with an over- all response (OR) rate of 70%. 7,8 This review summarizes the available data on the fl udarabine in the treatment of patients with non- Hodgkin's lymphomas (NHL). A literature search on fl udarabine for lymphomas was undertaken to identify published guidelines, meta-analyses, systematic literature reviews and controlled clinical trials using MEDLINE databases. No evidence-based guidelines for the use of fl udarabine have been found for the review. Pooling of data of cases from different studies for joint analysis was impractical for the reason that patients with heterogeneous characteristics (age, lymphoma subtype, prognostic factors, previous treatments etc) might have been included. The main goal of this study is to evaluate the major- ity of published records on fl udarabine and to analyze the indications for the administration, the advantages and disadvantages of this drug in order to defi ne its right current place in the treatment of lymphoma patients.