title: Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma.
abstract: OBJECTIVE
  To compare the long-term outcome of patients with previously untreated follicular lymphoma (FL) needing therapy, after treatment with cyclophosphamide, vincristine and prednisone (CVP) versus CVP plus rituximab (R-CVP) and to evaluate the predictive value of known prognostic factors after treatment with R-CVP.
  
  
  METHODS
  Patients with previously untreated CD20-positive stage III/IV FL were randomly assigned to eight cycles of R-CVP (n = 159) or CVP alone (n = 162). The median follow-up period was 53 months.
  
  
  RESULTS
  The primary end point-time to treatment failure (TTF), which included patients without a response after four cycles as an event-was significantly prolonged in patients receiving R-CVP versus CVP (P < .0001). Improvements in all other end points, including overall and complete response rates (P < .0001), time to progression (TTP; P < .0001), response duration (P < .0001), time to next antilymphoma treatment (P < .0001), and overall survival (OS; P = .029; 4-year OS: 83% v 77%;) were achieved with R-CVP versus CVP alone. Univariate analyses demonstrated an improvement in TTP with R-CVP versus CVP irrespective of the Follicular Lymphoma International Prognostic Index (FLIPI) subgroup, the International Prognostic Index (IPI) subgroup, baseline histology, and the presence or absence of B symptoms or bulky disease. By multivariate analysis, FLIPI retains a strong predictive power for TTP in the presence of the trial treatment effect.
  
  
  CONCLUSIONS
  Analysis of all outcome measures, including OS, confirm the benefit of adding R to CVP in the front-line treatment of FL.
authors.affiliation: Department of Haematology, Addenbrooke's Hospital, Cambridge, UK. Robert.Marcus@kch.nhs.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Marcus
authors.forename: Kevin
authors.initials: K
authors.lastname: Imrie
authors.forename: Philippe
authors.initials: P
authors.lastname: Solal-Celigny
authors.forename: John V
authors.initials: JV
authors.lastname: Catalano
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: João C
authors.initials: JC
authors.lastname: Raposo
authors.forename: Fritz C
authors.initials: FC
authors.lastname: Offner
authors.forename: José
authors.initials: J
authors.lastname: Gomez-Codina
authors.forename: Andrew
authors.initials: A
authors.lastname: Belch
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wassner-Fritsch
authors.forename: George
authors.initials: G
authors.lastname: Stein
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone