Fludarabine: new indication. First-line treatment of CLL: unconvincing evidence.

(1) Oral chlorambucil is the reference first-line treatment for patients with symptomatic chronic lymphocytic leukaemia. Intravenous fludarabine is a second-line option. (2) The indications for intravenous fludarabine have now been extended to cover first-line use. (3) The clinical evaluation dossier mainly contains data from two unblinded comparative trials. One trial compared intravenous fludarabine with chlorambucil in 509 patients for one year; the complete remission rate was significantly higher in the group receiving intravenous fludarabine (20% versus 4%) but, after 62 months of follow-up, the survival rate was no different (about 50% in both groups). Note that the dose of chlorambucil used in this trial may have been inadequate. (4) The other unblinded trial included 938 patients treated for six months with fludarabine, the CAP protocol, or the CHOP protocol. The median survival time did not differ among the three groups (67 to 70 months). (5) In the trial versus chlorambucil, the incidence of serious adverse events was significantly higher in the fludarabine group (55% of patients, versus 44%). The commonest serious adverse events were neutropenia, other haematological disturbances, and infections. (6) Oral chlorambucil is more convenient than intravenous fludarabine, which necessitates five infusions per month. Intravenous fludarabine costs 10 times more than oral chlorambucil. (7) In practice, chlorambucil remains the reference first-line treatment for chronic lymphocytic leukaemia.