Advanced-stage
follicular lymphoma (FL) and
mantle cell lymphoma (MCL) cannot be cured using conventional
chemotherapy.
Fludarabine, the most widely used
purine analog, exhibits a particularly high level of activity against
small lymphocytic lymphoma and
chronic lymphocytic leukemia (CLL). Numerous studies have investigated the efficacy of
fludarabine as a single agent or in combination with other
cytostatic compounds in the treatment of FL and MCL. Hematologic toxicity is the most commonly observed adverse event in patients treated with
fludarabine, but serious infectious complications are relatively rare.
Fludarabine monotherapy has proven to be particularly effective in the treatment of FL; however, complete responses (CRs) are observed in only approximately 20-40% of all cases. In contrast, combinations containing
fludarabine and
anthracyclines or
alkylating agents have yielded superior response rates and longer periods of progression-free survival (PFS), and the addition of the anti-CD20 antibody
rituximab appears to yield even better results. In a randomized trial, an immunochemotherapy regimen consisting of a
fludarabine-containing combination and
rituximab resulted in superior remission and survival rates compared with the
fludarabine-containing combination alone. In summary,
fludarabine has proven to be a safe and effective agent in the treatment of indolent
lymphoma. In particular, combinations containing
fludarabine,
anthracyclines and/or
alkylating agents, and
rituximab have yielded remarkable CR and PFS rates. Consequently, current research efforts have focused on the use of
fludarabine-containing combinations in the first-line treatment of FL and MCL.