Fludarabine, Cyclophosphamide and Mitoxantrone in Relapsed or Refractory Chronic Lymphocytic Leukemia and Low Grade Non-Hodgkin's Lymphoma

Abstract

A regimen combining fludarabine, cyclophosphamide and mitoxantrone (FCM) was used to treat 29 patients with relapsed or refractory chronic lymphocytic leukemia (CLL, N = 24) and low-grade non-Hodgkin's lymphoma (NHL, N = 5) based on evidence suggesting synergism between the 3 drugs. Patients were treated with mitoxantrone 5mg/m2 i.v. day 1 only, fludarabine 25 mg/m2 i.v. for 3 days or 24 mg/m2 orally for 5 days, cyclophosphamide 250 mg/m2 i.v. for 3 days or 150 mg/m2 orally for 5 days inclusive. Eighteen patients had previously received fludarabine and most were heavily pretreated with 40% having >2 prior treatments. A median number of 4 FCM courses (range of 1-9) were given. The response rate was 78.5%: 32% complete remission, 25% nodular partial remission, 21.5%, partial remission. Median duration of response was 19 months and median survival was 42 months. Sixteen patients (57%) developed neutropenia to < 0.5 x 10(9)/l and 12 (43%) infectious complications. Four patients developed large cell lymphoma (Richter's syndrome) and 2 acute myeloid leukemia. FCM is a useful combination for relapsed or refractory CLL and low grade NHL with high response rates and long duration of response. The role of FCM as first line therapy deserves study as well as its combination with the monoclonal antibody Rituximab.

Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease Eradication

“…This regimen has proved to have an important antitumor activity in patients with heavily pretreated patients with CLL, including the achievement of MRD-negative CRs (9,23).…”

“…Based on a number of in vitro and in vivo studies by others (23) and ourselves (16,17), we developed a combination chemotherapy, including fludarabine, cyclophosphamide, and mitoxantrone (FCM) that has proved to be highly effective in patients with either relapsed or refractory CLL (9,23).…”

A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia

“…The combination of fludarabine, cyclophosphamide and mitoxantrone (FCM) has previously been reported in two trials of 60 patients and 29 patients who had relapsed/refractory CLL (Bosch et al, 2002;Hendry et al, 2004). The ORRs were 78% and 79% respectively, with 30(50%) patients and 9(32%) patients achieving a CR.…”

Rituximab maintenance after first-line therapy with rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia

“…As with other B-cell malignancies, the use of rituximab maintenance after induction treatment suggests a benefit in sustaining the response duration in patients with CLL. 14 Based on data obtained from in vitro and in vivo studies, [29][30][31][32] we developed a combination chemotherapy including fludarabine, cyclophosphamide, and mitoxantrone (FCM). The encouraging responses achieved with this combination in patients with CLL, both previously treated and untreated, 29,33,34 prompted us to test its combination with rituximab.…”

“…14 Based on data obtained from in vitro and in vivo studies, [29][30][31][32] we developed a combination chemotherapy including fludarabine, cyclophosphamide, and mitoxantrone (FCM). The encouraging responses achieved with this combination in patients with CLL, both previously treated and untreated, 29,33,34 prompted us to test its combination with rituximab. Therefore, in November 2005, the Spanish Cooperative Group on CLL (GELLC) launched a phase 2 clinical trial aimed at investigating the feasibility, response, and toxicity of a treatment strategy consisting of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) as initial treatment followed by rituximab as maintenance therapy.…”