Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia

J Clin Oncol. 2009 Sep 10;27(26):4378-84. doi: 10.1200/JCO.2008.20.8389. Epub 2009 Aug 3.

Abstract

Purpose: 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).

Patients and 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.

Conclusion: Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Bendamustine Hydrochloride
  • Chlorambucil / adverse effects
  • Chlorambucil / therapeutic use*
  • Disease-Free Survival
  • Female
  • Fever / chemically induced
  • Follow-Up Studies
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neutropenia / chemically induced
  • Nitrogen Mustard Compounds / adverse effects
  • Nitrogen Mustard Compounds / therapeutic use*
  • Thrombocytopenia / chemically induced
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • Chlorambucil
  • Bendamustine Hydrochloride