High dose
chlorambucil has been shown to be an effective single-agent treatment in
chronic lymphocytic leukemia (CLL), and to be useful as part of
combination chemotherapy in low-grade non-Hodgkin's (NHL) and
Hodgkin's disease (HD). In general, it is well tolerated and can be used in an outpatient setting. The optimum dose of
chlorambucil has not been defined and there are numerous different dosing schedules available. Pharmacokinetic studies suggest decreased bioavailability with successive cycles, probably due to accelerated metabolism. There is good evidence that regimens which use higher doses of
chlorambucil have a better outcome than standard dose
therapy. Most of the trials which have compared
chlorambucil with
fludarabine have not used a higher dose regimen of
chlorambucil and cannot truly be described as comparative. There is an increase in the incidence of grade 3 and 4
neutropenia and also of
sepsis with
fludarabine treatment, compared to
chlorambucil.
Fludarabine produces a higher initial response rate in CLL but no statistical difference has been shown in long term survival between
fludarabine and high dose
chlorambucil. In the treatment of
lymphoma, single agent
chlorambucil does not confer a durable remission. There have been good results with
combination chemotherapy regimens such as CID and PECC. The oral route of administration of these combinations makes them particularly useful as part of palliative
chemotherapy. A further point to consider is that
chlorambucil is very much cheaper than
fludarabine and other newer agents.
Chlorambucil should not automatically be overlooked in favor of more recently developed drugs such as
fludarabine. There is good evidence that the
drug is an effective treatment at a suitable dose, and there is a need for randomized trials to compare it fully with other current treatments.