Phase III Randomized Study of Bendamustine Compared With Chlorambucil in Previously Untreated Patients With Chronic Lymphocytic Leukemia

• Published in: Journal of clinical oncology Vol. 27; no. 26; pp. 4378 - 4384
• Main Authors: KNAUF, Wolfgang U, LISSICHKOV, Toshko, BECKER, Martin, FRICKE, Hans-Joerg, HUGUET, Francoise, DEL GIUDICE, Ilaria, KLEIN, Peter, TREMMEL, Lothar, MERKLE, Karlheinz, MONTILLO, Marco, ALDAOUD, Ali, LIBERATI, Anna, LOSCERTALES, Javier, HERBRECHT, Raoul, JULIUSSON, Gunnar, POSTNER, Gerhard, GERCHEVA, Liana, GORANOV, Stefan
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.09.2009
• Subjects: Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bendamustine Hydrochloride; Biological and medical sciences; Cancer and Oncology; Cancer och onkologi; Chlorambucil - adverse effects; Chlorambucil - therapeutic use; Clinical Medicine; Disease-Free Survival; Female; Fever - chemically induced; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Klinisk medicin; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; 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; Tumors; Antineoplastic agent; Phase III trial; Human; Malignant hemopathy; Chlorambucil; Alkylating agent; Chronic lymphocytic leukemia; Randomization; Bendamustine; Cancerology; Treatment; Nitrogen mustard; Lymphoproliferative syndrome; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2008.20.8389

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