title: Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study).
abstract: PURPOSE Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. PATIENTS AND METHODS Patients received cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m(2) for 3 days intravenously (CC regimen) or fludarabine at 25 mg/m(2) combined with cyclophosphamide at 250 mg/m(2) for 3 days intravenously (FC regimen), every 28 days for up to six cycles. The primary end point was complete response (CR) rate. Secondary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. RESULTS Of 423 randomly assigned patients (211 to CC and 212 to FC), 395 were evaluated in the final analysis. The CR and ORR reached 47% and 88% in the CC arm and 46% and 82% in the FC arm (P = .25 and P = .11, respectively). The median PFS was 2.34 years with CC and 2.27 years with FC (P = .51). OS and grade 3/4 treatment-related toxicity were also comparable. Moreover, we did not observe any significant differences in CC and FC efficacy across different patient prognostic subgroups that included patients with 17p13 (TP53 gene) deletion who had poor survival in both study arms. CONCLUSION Cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive CLL. Both combinations have unsatisfactory activity in patients with 17p13 (TP53 gene) deletion.
authors.affiliation: Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, 93-510 Lodz, ul. Ciołkowskiego 2, Poland. robaktad@csk.umed.lodz.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jamroziak
authors.forename: Joanna
authors.initials: J
authors.lastname: Gora-Tybor
authors.forename: Beata
authors.initials: B
authors.lastname: Stella-Holowiecka
authors.forename: Lech
authors.initials: L
authors.lastname: Konopka
authors.forename: Bernadetta
authors.initials: B
authors.lastname: Ceglarek
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Ilona
authors.initials: I
authors.lastname: Seferynska
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Piszcz
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Calbecka
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kostyra
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Dwilewicz-Trojaczek
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszyñska
authors.forename: Krystyna
authors.initials: K
authors.lastname: Zawilska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Andrzej
authors.initials: A
authors.lastname: Zdunczyk
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Potoczek
authors.forename: Magdalena
authors.initials: M
authors.lastname: Piotrowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.forename: Jerzy Z
authors.initials: JZ
authors.lastname: Blonski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D017338:Cladribine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine