title: Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study.
abstract: OBJECTIVE
  Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL.
  
  
  METHODS
  Patients with first-line CLL were treated with rituximab (375 mg/m(2) on day 1, cycle one, and 500 mg/m(2) thereafter) plus chlorambucil (10 mg/m(2)/d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety.
  
  
  RESULTS
  A total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (range, 43 to 86 years), with patients having a median of seven comorbidities. Hematologic toxicities accounted for most grade 3/4 adverse events reported, with neutropenia and lymphopenia both occurring in 41% of patients and leukopenia in 23%. Overall response rates were 84%, with CR achieved in 10% of patients. Median progression-free survival was 23.5 months; median overall survival was not reached.
  
  
  CONCLUSIONS
  These results compare favorably with previously published results for chlorambucil monotherapy, suggesting that the addition of rituximab to chlorambucil may improve efficacy with no unexpected adverse events. R-chlorambucil may improve outcome for patients who are ineligible for fludarabine-based treatments.
authors.affiliation: Peter Hillmen, Abraham Varghese, and Andy Rawstron, St James's Institute of Oncology; Dena Cohen, University of Leeds, Leeds; John G. Gribben, Barts and the London School of Medicine; Claire E. Dearden, Royal Marsden Hospital; Amit Nathwani, University College London, London; George A. Follows, Addenbrooke's Hospital, Cambridge; Donald Milligan, Heartlands Hospital, Birmingham; Hazem A. Sayala, Hull and East Yorkshire Hospitals, Hull; Paul Moreton, Pinderfields General Hospital, Wakefield; David G. Oscier, Royal Bournemouth Hospital, Bournemouth; Daniel B. Kennedy, Leicester Royal Infirmary, Leicester; Andrew R. Pettitt, Royal Liverpool and Broadgreen University Hospitals National Health Service Trust, Liverpool; Christopher F.E. Pocock, East Kent Hospitals, Canterbury, United Kingdom; and Stephan Oertel, F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: George A
authors.initials: GA
authors.lastname: Follows
authors.forename: Donald
authors.initials: D
authors.lastname: Milligan
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Sayala
authors.forename: Paul
authors.initials: P
authors.lastname: Moreton
authors.forename: David G
authors.initials: DG
authors.lastname: Oscier
authors.forename: Claire E
authors.initials: CE
authors.lastname: Dearden
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kennedy
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pettitt
authors.forename: Amit
authors.initials: A
authors.lastname: Nathwani
authors.forename: Abraham
authors.initials: A
authors.lastname: Varghese
authors.forename: Dena
authors.initials: D
authors.lastname: Cohen
authors.forename: Andy
authors.initials: A
authors.lastname: Rawstron
authors.forename: Stephan
authors.initials: S
authors.lastname: Oertel
authors.forename: Christopher F E
authors.initials: CF
authors.lastname: Pocock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects; D015897:Comorbidity; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D002699:Chlorambucil; D000069283:Rituximab