Background: Thirty-six patients with relapsing or refractory chronic lymphocytic leukemia were entered into a Phase II study of the Eastern Cooperative Oncology Group.
Methods: A modified VAD regimen was given: a 96-hour infusion of 1.6 mg vincristine and 36 mg/m2 doxorubicin with dexamethasone 40 mg by mouth daily for 4 days every 3 weeks. The treatment was continued until two cycles beyond maximal response, which was evaluated after two and six cycles.
Results: Of the 33 evaluable patients, 7 (21%) achieved a partial response (PR), with no complete remissions. One-third of the patients (11 of 33) had progressive disease and 15 of 33 (45%) had stable disease, as defined by the National Cancer Institute Working Group criteria. The median duration of PR was 6.5 months, with a median survival time of 14.8 months. A PR was achieved by 3 of 19 patients (16%) who had received prior vincristine +/- doxorubicin and 4 of 14 patients (28%) who had not received vincristine or doxorubicin. Of the nine patients whose disease was refractory to prior therapy, five (55%) achieved a PR. The neurotoxicity of VAD was reduced by decreasing the frequency of the dexamethasone, but 22 of 36 (61%) patients still became infected. Only on infection (2.8%) was life threatening, and there were no infectious deaths.
Conclusions: Because fludarabine has shown superior responses, VAD should be reserved for patients who do not respond to alkylating agents and fludarabine and in whom alternative treatments are not appropriate.