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.
Robak
Tadeusz
T
Department of Hematology, Medical University of Lodz, Poland. robaktad@csk.umed.lodz.pl
Blonski
Jerzy Z
JZ
Gora-Tybor
Joanna
J
Jamroziak
Krzysztof
K
Dwilewicz-Trojaczek
Jadwiga
J
Tomaszewska
Agnieszka
A
Konopka
Lech
L
Ceglarek
Bernadetta
B
Dmoszynska
Anna
A
Kowal
Malgorzata
M
Kloczko
Janusz
J
Stella-Holowiecka
Beata
B
Sulek
Kazimierz
K
Calbecka
Malgorzata
M
Zawilska
Krystyna
K
Kuliczkowski
Kazimierz
K
Skotnicki
Aleksander B
AB
Warzocha
Krzysztof
K
Kasznicki
Marek
M
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