Fludarabine and Cyclophosphamide Using An Attenuated Dose Schedule Is a Highly Effective Regimen for Patients with Indolent Lymphoid Malignancies

BACKGROUND. Preclinical data have supported the use of fludarabine and cyclophosphamide (FC) in combination for the treatment of indolent lymphoid malignancies. Previously reported schedules were highly effective, but were complicated by significant myelotoxicity and infectious complications. In the current study, the authors analyzed their experience with an attenuated dose regimen to determine whether equivalent efficacy could be achieved with reduced toxicity. METHODS. Sixty-four patients with indolent lymphoid malignancies were treated with intravenous fludarabine at a dose of 25 mg/m² and cyclophosphamide at a dose of 250 mg/m², each given on Days 1-3 for a median of 4 cycles. The median age of the patients was 60 years. Nineteen percent of the patients were previously untreated, and 45% had refractory disease; the patients had received a median of 2 prior therapies. With regard to histology, 41% of the patients had chronic lymphocytic leukemia or its variants, whereas the remainder of patients had low-grade non-Hodgkin lymphoma, predominantly follicule center cell lymphoma. RESULTS. A total of 237 cycles were delivered. The principal toxicities reported were neutropenia (NCI CTC Grade 4 in 17% of cycles) and infection (Grade ≥ 3 in 6% of cycles). The overall response rate and complete response rate were 86% and 29%, respectively. No significant difference could be discerned with regard to response rates for patients with untreated, recurrent, or refractory disease. CONCLUSIONS. The FC schedule used in the current study was found to be highly effective in patients with indolent lymphoid malignancies. Toxicity was lower compared with higher dose schedules, whereas efficacy appeared to be equivalent.