Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2).
In this prospective randomized trial, we compared the efficacy and toxicity of cladribine (2-CdA) alone to 2-CdA combined with cyclophosphamide (CC) or cyclophosphamide and mitoxantrone (CMC) in untreated progressive chronic lymphocytic leukemia (CLL). Study end points were complete response (CR), overall response, minimal residual disease (MRD), progression-free survival, overall survival, and toxicity. From January 1, 1998 to December 31, 2003, 508 patients from 15 hematology departments were randomized. Compared with 2-CdA, CMC induced higher CR rate (36% vs 21%, P = .004), and a trend for higher CR rate with CC was observed (29% vs 21%, P = .08). Furthermore, the percentage of patients who were in CR and were MRD negative was higher in CMC compared with 2-CdA (23% vs 14%, P = .042). There were no differences in overall response, progression-free survival, and overall survival among treatment groups. Grade 3/4 neutropenia occurred more frequently in CC (32%) and CMC (38%) than in 2-CdA (20%) (P = .01 and P = .004, respectively). Infections were more frequent in CMC compared with 2-CdA (40% vs 27%, P = .02). In conclusion, CMC used in first-line treatment of CLL results in a higher CR rate and suppresses MRD more efficiently than 2-CdA monotherapy, although associates with increased toxicity. No important differences in efficacy and toxicity were found between CC and 2-CdA regimens.
Department of Hematology, Medical University of Lodz, Poland. robaktad@csk.umed.lodz.pl
Tadeusz
T
Robak
Jerzy Z
JZ
Blonski
Joanna
J
Gora-Tybor
Krzysztof
K
Jamroziak
Jadwiga
J
Dwilewicz-Trojaczek
Agnieszka
A
Tomaszewska
Lech
L
Konopka
Bernadetta
B
Ceglarek
Anna
A
Dmoszynska
Malgorzata
M
Kowal
Janusz
J
Kloczko
Beata
B
Stella-Holowiecka
Kazimierz
K
Sulek
Malgorzata
M
Calbecka
Krystyna
K
Zawilska
Kazimierz
K
Kuliczkowski
Aleksander B
AB
Skotnicki
Krzysztof
K
Warzocha
Marek
M
Kasznicki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D017338:Cladribine / Q000008:administration & dosage* / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007239:Infections / Q000139:chemically induced; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D018365:Neoplasm, Residual; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction
D017338:Cladribine; D003520:Cyclophosphamide; D008942:Mitoxantrone