Low‐dose oral fludarabine plus cyclophosphamide in elderly patients with untreated and relapsed or refractory chronic lymphocytic Leukaemia

Abstract

Fludarabine plus cyclophosphamide (FC) at conventional doses is an effective treatment for chronic lymphocytic leukaemia (CLL). However, FC at standard doses may give hematological and non-hematological toxicity, predominantly in the elderly. Intravenous or oral low-dose FC regimens remain highly effective in elderly patients with Low-Grade Lymphomas other than CLL and are well tolerated. We tested efficacy and toxicity of oral FC at reduced doses in 26 elderly patients (median 71 years) with previously untreated (UT-CLL, n = 14) or relapsed/refractory CLL (R-CLL, n = 12), unfit for conventional treatments. Twentyfour-of-26 (92%) patients (14/14, 100% UT-CLL; 10/12, 83.5% R-CLL) obtained a response, with 12/26 (46%) complete responses (9/14, 64.2% in UT-CLL; 3/12, 25% in R-CLL). Non-hematological toxicity was mild and myelosuppression was documented in 8/26 (31%) patients (4/14, 28% UT-CLL; 4/12, 33% R-CLL). With a median follow-up of 24 months, median event-free survival was 48 months with no differences between UT-CLL and R-CLL and all responders were alive. Low-dose oral FC treatment showed good efficacy in both untreated and refractory/relapsed CLL. The treatment is useful in elderly patients who cannot benefit of more aggressive schedules and is easy to administer on an outpatient basis.

First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

“…5 Because the elderly patients included in British trial were selected to have very good physical condition and low comorbidity, an Italian monocentric phase II trial evaluated a dose-reduced FC regimen in elderly patients with CLL. 27 Using a low-dose FC regimen for first-line therapy in 26 elderly patients (median age 71) resulted in an overall response rate of 92%, with 46% complete responses. Similarly promising data were obtained by a chemoimmunotherapy regimen consisting of pentostatin, cyclophosphamide and rituximab.…”

Impact of dose intensity on outcome of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy for chronic lymphocytic leukemia

“…2 However, the intro- whereas another group has preferred oral F 25 mg/m 2 Days 1-4 + C 120 mg/m 2 Days 1-4. 5,6 More recently, Foon and coworkers have developed the FCR-Lite schedule using low doses of FC in combination with high-dose rituximab. 7,8 Finally, the French CLL study group is currently promoting FCR combination in young or fit elderly patients with oral F 40 mg/m 2 Days 1-3 + C 250 mg/m 2 Days 1-3 + R 375-500 mg/m 2 .…”

Management of Chronic Lymphocytic Leukemia in Elderly Patients

“…Trials evaluating chemotherapy in elderly or unfit patients have recently been conducted. Forconi et al [41] reported on the efficacy and toxicity of oral fludarabine plus cyclophosphamide at reduced doses in 26 elderly patients (median age 71 years) with previously untreated CLL (UT-CLL, n = 14) or relapsed/refractory CLL (R-CLL, n = 12) who were unfit for conventional treatments. Twenty-four patients (92%) obtained a response (14 [100%] in the UT-CLL group and 10 [83%] in the R-CLL group), including 12 complete responses (9 [64%] in the UT-CLL group and 3 [25%] in the R-CLL group; 46% overall).…”