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).
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.
Robak
Tadeusz
T
Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, 93-510 Lodz, ul. Ciołkowskiego 2, Poland. robaktad@csk.umed.lodz.pl
Jamroziak
Krzysztof
K
Gora-Tybor
Joanna
J
Stella-Holowiecka
Beata
B
Konopka
Lech
L
Ceglarek
Bernadetta
B
Warzocha
Krzysztof
K
Seferynska
Ilona
I
Piszcz
Jaroslaw
J
Calbecka
Malgorzata
M
Kostyra
Aleksandra
A
Dwilewicz-Trojaczek
Jadwiga
J
Dmoszyñska
Anna
A
Zawilska
Krystyna
K
Hellmann
Andrzej
A
Zdunczyk
Andrzej
A
Potoczek
Stanislaw
S
Piotrowska
Magdalena
M
Lewandowski
Krzysztof
K
Blonski
Jerzy Z
JZ
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
D017338:Cladribine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine