Current approaches to the chemotherapy of B-cell chronic lymphocytic leukemia: a review

Standard therapy has not substantially improved the outcome of patients with chronic lymphocytic leukemia (CLL). However, an increased understanding of the biology and immunology of CLL, and the availability of several new and active chemotherapy agents (eg, fludarabine, 2'-deoxycoformycin [DCF], 2-chlorodeoxyadenosine [CDA]) has stimulated enthusiasm for clinical trials. DCF induces CRs or PRs in 25% of heavily treated patients. Fludarabine has been associated with a response rate of greater than 50% in previously treated patients, and greater than 70% in untreated patients, with almost a third of these achieving a CR. Currently, phase I and II clinical trials are evaluating combinations of these drugs with each other or with conventional agents (eg, fludarabine/chlorambucil [CLB]/prednisone [P]; DCF/CLB/P; fludarabine/DCF; fludarabine/P) in previously treated patients. To facilitate comparison of these regimens, each study is adhering to the NCl-Working Group guidelines for eligibility and response criteria, and toxicity assessment. A collaborative phase III trial will then compare the most promising of these regimens with "standard" chemotherapy in previously untreated patients. The widespread availability of these clinical trials will allow clinicians ready access to the new treatments.