Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia.
OBJECTIVE
This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL).


METHODS
Patients (<or= 75 years of age) were randomly assigned to receive bendamustine 100 mg/m(2)/d intravenously on days 1 to 2, or chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee.


RESULTS
A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P < .0001). More patients showed complete responses with bendamustine than with chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P < .0001). Bendamustine was also associated with an improvement in duration of remission, compared with chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients.


CONCLUSIONS
Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.
Knauf
Wolfgang U
WU
Onkologische Gemeinschaftspraxis, Frankfurter Diakonie Kliniken, Im Pruefling 17-19, 60389 Frankfurt, Germany. wolfgang.knauf@telemed.de
Lissichkov
Toshko
T
Aldaoud
Ali
A
Liberati
Anna
A
Loscertales
Javier
J
Herbrecht
Raoul
R
Juliusson
Gunnar
G
Postner
Gerhard
G
Gercheva
Liana
L
Goranov
Stefan
S
Becker
Martin
M
Fricke
Hans-Joerg
HJ
Huguet
Francoise
F
Del Giudice
Ilaria
I
Klein
Peter
P
Tremmel
Lothar
L
Merkle
Karlheinz
K
Montillo
Marco
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D002699:Chlorambucil / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D002699:Chlorambucil; D000069461:Bendamustine Hydrochloride