title: Bortezomib ADDED to R-CVP is safe and effective for previously untreated advanced-stage follicular lymphoma: a phase II study by the National Cancer Institute of Canada Clinical Trials Group.
abstract: OBJECTIVE
  Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL.
  
  
  METHODS
  This is a phase II multicenter trial adding bortezomib (1.3 mg/m(2) days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed.
  
  
  RESULTS
  Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%).
  
  
  CONCLUSIONS
  The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.
authors.affiliation: National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada. lsehn@bccancer.bc.ca
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: David
authors.initials: D
authors.lastname: MacDonald
authors.forename: Sheldon
authors.initials: S
authors.lastname: Rubin
authors.forename: Guy
authors.initials: G
authors.lastname: Cantin
authors.forename: Morel
authors.initials: M
authors.lastname: Rubinger
authors.forename: Bernard
authors.initials: B
authors.lastname: Lemieux
authors.forename: Sanraj
authors.initials: S
authors.lastname: Basi
authors.forename: Kevin
authors.initials: K
authors.lastname: Imrie
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sussman
authors.forename: Bingshu E
authors.initials: BE
authors.lastname: Chen
authors.forename: Marina
authors.initials: M
authors.lastname: Djurfeldt
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Stephen
authors.initials: S
authors.lastname: Couban
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002170:Canada; D003520:Cyclophosphamide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D014750:Vincristine; D000069286:Bortezomib; D003520:Cyclophosphamide; D011241:Prednisone