High-dose chlorambucil for the treatment of chronic lymphocytic leukaemia and low-grade non-Hodgkin's lymphoma.

ABSTRACT

Chlorambucil has been used for many years for the treatment of low-grade B-cell lymphoproliferative disorders, including chronic lymphocytic leukaemia and low-grade non-Hodgkin's lymphoma. There is evidence in the literature that increasing the dose of chlorambucil produces better results than 'standard' doses in terms of response rates and overall survival. There is also evidence that this approach may be at least as effective as the use of fludarabine, as well as being very much less expensive. We describe a high-dose chlorambucil (HDC) regimen, which involves a sustained but intermittent dose of chlorambucil, i.e. 30 mg/d for 4 d per week for 4 weeks, followed by a further four courses at fortnightly intervals for 8 weeks (a total of eight 4-d courses) given as a single drug over an initial 12-week period. The outcome of treatment in previously treated and untreated patients was excellent, with a median time to treatment failure of 33 months for the patient cohort overall and for previously treated and chemotherapy-naive patients of 13 and 104 months respectively. In patients previously treated with fludarabine, 78% had a response. Autoimmune haemolytic anaemia was reversed in one patient. Toxicity, both haematological and other, was minimal. We propose that escalated-dose chlorambucil regimens should be compared with fludarabine in randomized controlled trials, rather than 'standard' lower dose protocols.