Oral fludarabine and cyclophosphamide as front-line chemotherapy in patients with chronic lymphocytic leukemia. The impact of biological parameters in the response duration.
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. Thirty-seven 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 IgVH-mutated 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.
Laurenti
Luca
L
Istituto di Ematologia, Policlinico A Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy. l.laurenti@rm.unicatt.it
Tarnani
Michela
M
De Padua
Laura
L
Efremov
Dimitar G
DG
Zini
Gina
G
Garzia
Mariagrazia
M
Piccirillo
Nicola
N
Chiusolo
Patrizia
P
Sorà
Federica
F
Innocenti
Idanna
I
Sica
Simona
S
Leone
Giuseppe
G
D000284:Administration, Oral; D000368:Aged; D000740:Anemia / Q000139:chemically induced*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009503:Neutropenia / Q000139:chemically induced*; D012074:Remission Induction; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine