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Lookup NU author(s): Professor Stephen Proctor
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Chlorambucil has been used as single agent oral chemotherapy for CLL and LG-NHL for many years, and is often given in combination with corticosteroids with or without a vinca alkaloid. The dose of chlorambucil has varied from 2-10mg daily for periods of one week to several months. For relapsed or resistant patients we have developed a protocol of single agent high dose chlorambucil (HDC) at a dose of 30mg daily for 4 days per week for 4 weeks, followed by four more courses of the same regimen at 2 week intervals. The protocol has also more recently been applied to a number of previously untreated patients. We report on the efficacy and toxicity of this regimen in 34 patients treated since 1986. The patients were 22M, 12F aged 27-80 at the time of treatment, from 7 hospitals in the Northern Health Region of the United Kingdom. The diagnosis was CLL in 24 cases, LG-NHL in 8, prolymphocytic leukaemia (B-PLL) in 1 and Waldenstrom's macroglobulinaemia (WM) in 1. The CLL patients were Binet stage C ( 16), B (4) and A (4) and the LG-NHL patients all stage IV. Previous treatment included standard dose chlorambucil in 12, fludarabine in 9, prednisolone in 5, CHOP or similar regimens in 4, radiotherapy in 3, interferon in 3, chlorambucil with idarubicin and dexamethasone (CID) in 2, ChlVPP 2, methylprednisolone 2. cyclophosphamide 1, azathioprine 1 and IV1G 1. Number of previous regimens ranged from 0-4. Thirteen patients were previously untreated. Time from initial diagnosis to HDC varied from 0-120 months and number of courses of HDC from 1-19 (patients receiving less than 2 courses excluded from analysis of response). Of 32 analysable patients, 5 achieved CR. 3 nodular PR, 21 PR, 3 NR. In August 2000, 31 patients remained alive and 3 had died. Survival from diagnosis was 6-175 months, from HDC therapy 1-175 months and time to next treatment following HDC 0-104 months (further treatment needed in 11 patients, none in 20, 3 died). No significant toxicity was seen in 15 patients, infection in 5, anaemia in 4 ( 1 with A1HA), pancytopenia in 3, nausea in 2, rash in 2, insomnia in 1, transient tender lymph nodes in 1 and seizure in 2. Convulsions are a recognised complication of HDC, especially in the elderly, and we recommend a prophylactic anticonvulsant in patients over 60 years. High dose chlorambucil achieved a significant response in previously treated and untreated patients with an overall CR rate of 16%, nodular PR 9%, PR 66%, NR 9%. The majority of patients (62%) had been previously treated, in some cases with multiple regimens. Responses occurred in patients resistant to or relapsing after fludarabine. Dose escalation of chlorambucil is safe and the HDC regimen described here could be incorportated in future clinical trials in CLL and LG-NHL.
Author(s): Summerfield GP, Mounter P, Proctor SJ
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2001
Volume: 96
Issue: 11
Pages: 295B-295B
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Notes: Conference: Annual meeting of the American Society of Hematologists. Abstract 5017.
