title: Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma.
abstract: OBJECTIVE
  To determine overall response rate (ORR), time to progression (TTP), and duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab, and evaluate safety/tolerability, in patients with relapsed or refractory CD20(+) follicular lymphoma (FL) or marginal-zone lymphoma.
  
  
  METHODS
  Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m(2) twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or bortezomib 1.6 mg/m(2) weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles; arm B) plus rituximab 375 mg/m(2) weekly for 4 weeks (both arms). Response/progression was determined by International Workshop Response Criteria using oncologist/radiologist-adjudicated data from independent radiology review and investigator assessment.
  
  
  RESULTS
  Eighty-one patients (arm A, n = 41; arm B, n = 40) were enrolled. Dose-intensity was higher in arm A; mean total bortezomib received was similar between arms (18.5 and 17.1 mg/m(2)). In arm A, ORR was 49% (14% complete response [CR]/CR unconfirmed [CRu]), median TTP was 7.0 months, and median DOR was not reached. In arm B, ORR was 43% (10% CR/CRu), and median TTP/DOR were 10.0/9.3 months. The weekly combination regimen seemed better tolerated. Grade 3 or worse adverse events seemed more common in arm A (54%) versus arm B (35%), including thrombocytopenia (10% v 0%) and peripheral neuropathy (10% v 5%), but diarrhea seemed less frequent (7% v 15%). No grade 4 toxicities were reported in arm B.
  
  
  CONCLUSIONS
  Both bortezomib plus rituximab regimens seem feasible in relapsed or refractory indolent lymphomas. The more convenient weekly combination regimen is being compared with single-agent rituximab in an ongoing phase III study in relapsed FL.
authors.affiliation: Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. devos@mednet.ucla.edu
authors.forename: Sven
authors.initials: S
authors.lastname: de Vos
authors.forename: André
authors.initials: A
authors.lastname: Goy
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Mansoor N
authors.initials: MN
authors.lastname: Saleh
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Robert
authors.initials: R
authors.lastname: Belt
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.forename: Mark
authors.initials: M
authors.lastname: Knapp
authors.forename: Lowell
authors.initials: L
authors.lastname: Hart
authors.forename: Dipti
authors.initials: D
authors.lastname: Patel-Donnelly
authors.forename: Martha
authors.initials: M
authors.lastname: Glenn
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Gregory
authors.forename: Charles
authors.initials: C
authors.lastname: Holladay
authors.forename: Tracy
authors.initials: T
authors.lastname: Zhang
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Boral
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib