title: 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.
authors.affiliation: Queen Elizabeth Hospital, Gateshead, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. geoffrey.summerfield@exchange.gatesh-tr.northy.nhs.uk
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Summerfield
authors.forename: Penelope R A
authors.initials: PR
authors.lastname: Taylor
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mounter
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Proctor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000150:complications / Q000188:drug therapy; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D002699:Chlorambucil / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D002699:Chlorambucil; D014740:Vidarabine; C024352:fludarabine