Fludarabine

Abstract

Fludarabine is a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Noncomparative studies have shown response rates in patients with chronic lymphocytic leukaemia (CLL) that appear to be at least equivalent to those achieved with conventional therapy. Prolymphocytic leukaemia, a form of CLL which is often resistant to conventional chemotherapy, has also responded to treatment with fludarabine. Fludarabine combined with prednisone has also induced good response rates in patients with CLL but the limited data suggest that this does not offer an advantage over fludarabine alone. Several clinical trials have demonstrated a good cytoreductive response in patients with advanced, low grade non-Hodgkin's lymphoma, particularly that of follicular histology. Preliminary evidence indicates fludarabine in combination with cytarabine has therapeutic activity as salvage therapy in patients with acute leukaemia. Myelosuppression has been the major dose-limiting adverse effect reported in clinical trials of fludarabine. A reduction in CD4+ cell count may be associated with the increased incidence of fever and opportunistic infections in fludarabine recipients. Nausea and vomiting have also been commonly reported, but these are generally mild to moderate in severity. Reversible neurotoxicity has also been occasionally reported. Thus, fludarabine appears to offer a viable alternative to currently used treatments in CLL and low grade non-Hodgkin's lymphoma. Other potential areas of use for fludarabine include acute leukaemias. Waldenstrom's macroglobulinaemia and mycosis fungoides. However, trials of fludarabine in comparison with currently used therapies and also in combination with other antineoplastic agents are required to fully define its role in the treatment of lymphoid malignancies. In addition, because relapse in these diseases is common, long term trials assessing improvement in survival duration and quality of life would be of value.

Volumetric modulated arc therapy total body irradiation in pediatric and adolescent/young adult patients undergoing stem cell transplantation: Early outcomes and toxicities

“…24,25 Fludarabine and antithymocyte globulin are also commonly reported to cause nausea and vomiting. 26,27 Direct attribution of toxicities to TBI alone are difficult, as the timing of chemotherapy conditioning overlaps with the delivery of radiation therapy. Despite the possibility of the toxicities being multifactorial, the toxicities reported in our cohort are comparable to prior studies, including those that have utilized helical tomotherapy (HT).…”

Population Pharmacokinetics of Fludarabine in Children and Adults during Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation

“…Renal function was evaluated as a covariate, since fludarabine is predominantly eliminated renally [ 10 , 21 ]. As creatinine levels were not measured daily, the mean value of available individual creatinine values between day − 7 and day 0 prior to infusion were used.…”

Resistance to fludarabine-induced apoptosis in Epstein-Barr virus infected B cells

“…Fludarabine is an adenosine nucleoside analogue that has been extensively used to treat haematological malignancies (Ross et al, 1993). Although it was shown to inhibit DNA synthesis,¯udarabine can also inhibit RNA synthesis, methylation, DNA repair and nicotinamide adenine metabolism.…”