Fludarabine and epirubicin in the treatment of chronic lymphocytic leukaemia: A German multicenter phase II study

Purpose: Fludarabine has been reported to be the most effective single-agen t in previously treated chronic lymphocytic leukae mia (CLL). Based on the in vitro synergism of fludarabine with anthracyclines and on results showin g a higher efficacy of CHOP against COP we attempted to improve treatment r esults with a combination of fludarabine and an anthracycline. Patients and methods: The aim of the multicenter study was to evaluate the rate and duration of remissions and investigate the toxic and immunosuppres sive effects of fludarabine and epirubicin in the treatment of CLL in Binet stages B and C as first-line therapy or in first relapse. Thirty-eight pat ients were treated with fludarabine 25 mg/m(2) on days 1-5 and epirubicin 2 5 mg/m(2) on days 4 and 5. Results: The overall response rate (OR) was 82% (95% confidence interval (9 5% CT): 66%-92%) with a CR rate of 32% (95% CT: 18%-49%). For the 25 previo usly untreated patients the OR was 92% (95% CT: 74%-99%) including 40% CRs (95% CT: 21%-61%). Granulocytopenia grade 3 occurred in 23% of all evaluabl e cycles, and grade 4 in 17%. The median remission duration was 19 months ( range 6-37 months). Conclusion: The results show that the combination of fludarabine and epirub icin is tolerable and highly effective in the treatment of CLL. With the ad dition of epirubicin to fludarabine, it appears possible to achieve a highe r response rate and a more rapid response, especially of nodal manifestatio ns. This regimen can be administered in an outpatient facility except for t he first cycle because of the risk of a tumour lysis. The possible benefit of the combination presented here in the treatment of CLL in comparison to single-agent fludarabine treatment is presently under study in a prospectiv e randomised multicenter study.