3 The Technology
3.1 Fludarabine is a cytotoxic agent of the antimetabolite class. It is currently licensed for patients with B-cell CLL with sufficient bone marrow reserve and who have not responded to, or whose disease has progressed during or after, treatment with at least one standard alkylating-agent containing regimen.
3.2 It is administered either as an intravenous infusion (over 30 minutes) or orally. This is repeated each day for 5 days, and this cycle is then repeated every 28 days for up to 6 cycles. The drug acquisition cost (for either intravenous or oral formulation) of a course of 6 cycles is about £3,900. Each intravenous infusion requires a day-case admission to hospital, while the oral preparation usually needs only a small number of hospital visits.
3.3 Although the immediate side effects of fludarabine (nausea, vomiting, alopecia) are less troublesome than those of CHOP, there are frequent haematological adverse events (granulocytopenia, anaemia and thrombocytopenia), as well as other important long-term effects. Of these, the principal effect is T-cell immunosuppression, leading to a recommendation for prophylactic antibiotic treatment against Pneumocystis carinii pneumonia, and irradiation of all blood products given to the patient to prevent transfusion-related graft-versus-host disease. Concurrent corticosteroids increase this risk due to the additive lymphocytic activity and should therefore be avoided unless otherwise indicated. Additionally, autoimmune haemolytic anaemia is relatively common in patients with CLL. It occurs in about 1% to 5% of patients receiving fludarabine as a second line treatment. The haemolysis is often severe, may be difficult to treat, and is potentially fatal.
3.4 Nevertheless, on a day-to-day basis, fludarabine is generally tolerated better than conventional second line chemotherapy regimens, particularly in patients currently considered too frail to withstand combination therapies.