title: Oral fludarabine and cyclophosphamide as front-line chemotherapy in patients with chronic lymphocytic leukemia. The impact of biological parameters in the response duration.
abstract: 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.
authors.affiliation: Istituto di Ematologia, Policlinico A Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy. l.laurenti@rm.unicatt.it
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Michela
authors.initials: M
authors.lastname: Tarnani
authors.forename: Laura
authors.initials: L
authors.lastname: De Padua
authors.forename: Dimitar G
authors.initials: DG
authors.lastname: Efremov
authors.forename: Gina
authors.initials: G
authors.lastname: Zini
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Garzia
authors.forename: Nicola
authors.initials: N
authors.lastname: Piccirillo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chiusolo
authors.forename: Federica
authors.initials: F
authors.lastname: Sorà
authors.forename: Idanna
authors.initials: I
authors.lastname: Innocenti
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
mesh_terms: 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
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine