title: Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study.
abstract: OBJECTIVE
  Bendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab.
  
  
  METHODS
  Patients received bendamustine 120 mg/m(2) intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety.
  
  
  RESULTS
  Seventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%).
  
  
  CONCLUSIONS
  Single-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population.
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester, 601 Elmwood Ave, Box 704, Rochester, NY, 14642, USA. Jonathan_Friedberg@URMC.Rochester.edu
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Philip
authors.initials: P
authors.lastname: Cohen
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: K Sue
authors.initials: KS
authors.lastname: Robinson
authors.forename: Andres
authors.initials: A
authors.lastname: Forero-Torres
authors.forename: Ann S
authors.initials: AS
authors.lastname: La Casce
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
authors.forename: Alberto
authors.initials: A
authors.lastname: Bessudo
authors.forename: Elber S
authors.initials: ES
authors.lastname: Camacho
authors.forename: Michael E
authors.initials: ME
authors.lastname: Williams
authors.forename: Richard H
authors.initials: RH
authors.lastname: van der Jagt
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Oliver
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride