Comparison between oral and intravenous fludarabine plus cyclophosphamide regime as front-line therapy in patients affected by chronic lymphocytic leukaemia: influence of biological parameters on the clinical outcome (original) (raw)
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British Journal of Haematology, 2008
A multicentre single-arm study testing the efficacy and toxicity of the oral combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with untreated B cell-chronic lymphocytic leukaemia. Oral FC demonstrated high efficacy with overall (OR) and complete response (CR) rates of 80% and 53%, respectively. Out of the 30 CR patients studied for Minimal Residual Disease (MRD) using 4-colour flow-cytometry and the 22 using Clonospecific polymerase chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median survival and median treatment-free interval had not been reached at 7 years of follow-up. Median progressionfree survival (PFS) was 5 years. Toxicity was acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia and infections, respectively. Gastrointestinal toxicity was mild. Oral FC demonstrated a high efficacy and an acceptable safety profile and may be considered as the standard first line treatment in chronic lymphocytic leukaemia.
Cancer, 2010
BACKGROUND: An oral formulation of fludarabine was introduced for use in chronic lymphocytic leukemia in 2001 following studies demonstrating the bioequivalence of a 40 mg/m 2 oral dose with a 25 mg/m 2 intravenous dose. We assessed retrospectively the efficacy of these two routes of administration in the LRF CLL4 trial. METHODS: A total of 777 patients were randomized from 1999-2004 to receive fludarabine, alone or with cyclophosphamide, or chlorambucil. In 2001, a protocol amendment allowed the oral formulation. There were 117 assessable patients who received fludarabine intravenously and 252 who received it orally. A total of 387 patients given chlorambucil acted as a control group. RESULTS: Patients given oral fludarabine were less likely to receive the full dose (P ¼ .0004) and experienced more, predominantly gastrointestinal, toxicity. Progression-free survival (PFS) and overall survival were not affected by the route of administration (PFS hazard ratio, 1.10; 95% confidence interval, 0.87-1.40), but the overall rate of response to treatment appeared to be lower with the oral formulation (P ¼ .003). However, patients recruited since 2001 were older (P ¼ .03) and were more likely to have TP53 deletion, and response rates after 2001 were also lower in the chlorambucil group. After excluding patients with TP53 deletion, no significant difference in outcome was attributable to the route of administration. CONCLUSIONS: Although the LRF CLL4 data suggest no important difference in the effectiveness of oral compared with intravenous fludarabine, randomized trials are needed to reliably evaluate this comparison, particularly in combination with rituximab. Meanwhile, it is important to monitor compliance and gastrointestinal side effects with the oral route and to switch to intravenous therapy if a reduced dose is being received.
Annals of Hematology, 2008
We tested the efficacy and safety of oral fludarabine and cyclophosphamide as front-line therapy in chronic lymphocytic leukemia (CLL) and assessed the influence of immunoglobulin variable region heavy chain (IgVH) gene mutation status, interphase cytogenetic abnormalities, and expression of ZAP-70 and CD38 on clinical outcome. Thirtyseven patients with previously untreated CLL received oral fludarabine (30 mg m 2 ) and oral cyclophosphamide (250 mg m 2 ) for three consecutive days every 4 weeks for six cycles. Eighteen patients had unmutated and 15 had mutated IgVH genes. Nine patients had the 'high risk' cytogenetic abnormality del(11q22.3) or del(17p13.1). Fifteen patients were ZAP-70-positive and eight patients were CD38-positive. Among the 35 valuable patients, 14 patients (40%) obtained a complete response and 13 (37%) a partial response. The median progression-free survival (PFS) was 23 months and median time to re-treatment (TTR) was 38 months. A significantly lower overall response rate (43% vs. 85%, p=0.011), a shorter PFS (22 vs. 27 months, p= 0.015), and a shorter TTR (22 vs. 40 months, p=0.031) were noticed in the 'high risk' cytogenetic abnormalities group; TTR was also shorter in IgVH-unmutated than in IgVHmutated patients (26 vs. 41 months, p=0.035). Hematologic toxicity included grade IV neutropenia (ten patients) and grade III/IV anemia (three patients). Gastrointestinal toxicity was mild and no patient required hospitalization. The oral combination of fludarabine and cyclophosphamide is an effective, safe, and well-tolerated regimen that, if confirmed with larger series, will be appropriate especially in patients with low risk biological parameters.
Annals of Medical and Health Sciences Research, 2018
Background: Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders. Many drugs were used for treatment of CLL, but efficacy of them is controversy. In present study, we compare survival of patients with CLL in three treatment regimens of fludarabine, chlorambucil and cyclophosphamide. Methods & Materials: In this historical cohort study, 83 patients with CLL whom participated in imposed war, enrolled to study. Of these, 39 patients received fludarabine (F), 23 patients received prednisone plus chlorambucil (C), and 21 patients received CAP (cyclophosphamide, doxorubicin, and prednisone). Overal survival (OS), Progression Free Survival (PFS), Complete Remission (CR), Partial Remission (PR) and Overall Remission (OR) were evaluated. For comparison, data entered to SPSS-18 & has been analyzed. P-value<0.05 were significant. Result: With a median follow up of 51 months, 16 (19.3%) patients died. Of this, 6 received Fludarabine, 5 received Chlorambucil,...