title: 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.
abstract: The fludarabine plus cyclophosphamide (FC) regimen was reported to be superior to chlorambucil or fludarabine alone in terms of complete response (CR), overall response (OR) and progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukaemia (CLL). In the present study, we compared the efficacy and toxicity of FC administered through oral and intravenous route in 65 untreated patients affected by advanced CLL. No statistical differences were noticed between the two routes of administration in terms of OR, PFS, time to re-treatment (TTR) and overall survival (OS) of analysed patients. We also assessed the influence on the clinical outcome of the mutation status of the immunoglobulin variable region heavy chain (IgVH) gene, of the cytogenetic abnormalities and of the expression of ZAP70 and CD38 in patients' primary samples. Among the 58 evaluable patients, 31 (53%) achieved a CR and 18 (31%) a partial response. The median PFS was 35 months, median TTR was 42 months and median OS was not reached after 45 months (range, 1-161). A significantly lower OR rate was noticed in patients with high-risk cytogenetic abnormalities (del 17p, del 11q). In this study, high-risk cytogenetic abnormalities and unmutated IgVH genes were independent predictors of TTR. These results underline the importance of biological stratifications in front-line treatment of CLL patients. We confirm that FC is an effective regimen with mild toxicities; it could be recommended for patients with low-risk biological parameters who represent, in our experience, about 30% of the total.
authors.affiliation: Istituto di Ematologia, Policlinico A Gemelli, Universita' Cattolica del Sacro Cuore, Rome, Italy. l.laurenti@rm.unicatt.it
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Laura
authors.initials: L
authors.lastname: De Padua
authors.forename: Michela
authors.initials: M
authors.lastname: Tarnani
authors.forename: Nicola
authors.initials: N
authors.lastname: Piccirillo
authors.forename: Paolo
authors.initials: P
authors.lastname: Falcucci
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.forename: Idanna
authors.initials: I
authors.lastname: Innocenti
authors.forename: Sara
authors.initials: S
authors.lastname: Marietti
authors.forename: Dimitar G
authors.initials: DG
authors.lastname: Efremov
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chiusolo
authors.forename: Gina
authors.initials: G
authors.lastname: Zini
authors.forename: Federica
authors.initials: F
authors.lastname: Sora'
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leone
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D015415:Biomarkers; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine