Chlorambucil--still not bad: a reappraisal.
Although chlorambucil has been used in the management of chronic lymphocytic leukemia (CLL) for 55 years, the optimal dose and treatment duration have not been established. We summarized data from 4 UK randomized CLL trials over the past 30 years in which chlorambucil, as a single agent, was one of the study arms. Overall response rates (ORR) ranged from 57% to 75% when using doses of 60-70 mg/m(2) per 28-day cycle. This compares favorably with an ORR of 31% to 55% in other studies that used lower doses. Response rates improved when patients received 6 or more courses. Studies that used chlorambucil as a comparator, at lower doses or with fewer courses, resulted in consistently lower ORR. Comparisons with single-agent fludarabine in 2 randomized trials (LRF CLL4 and German CLL5) showed similar progression-free survival. Chlorambucil compares favorably with fludarabine and bendamustine with respect to myelotoxicity, neutropenia, and fever, even at 70 mg/m(2) per cycle and in the elderly. Resistance to chlorambucil does not preclude a good response to newer treatments used as second-line treatment, which explains the good survival after progression observed in patients randomized to chlorambucil in LRF CLL4. Chlorambucil is currently being combined with anti-CD20 monoclonal antibodies in several phase II and III trials. It remains a useful drug for patients unfit to receive more intensive combinations. However, both the dose and duration of treatment are important.
Section of Haemato-Oncology, The Institute of Cancer Research, Sutton, United Kingdom. daniel.catovsky@icr.ac.uk
Daniel
D
Catovsky
Monica
M
Else
Sue
S
Richards
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D002699:Chlorambucil