title: Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
  
  
  METHODS
  Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles.
  
  
  RESULTS
  Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study.
  
  
  CONCLUSIONS
  Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 459, Houston, TX 77030, USA. ahgoy@mdanderson.org
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Frederick
authors.initials: F
authors.lastname: Hagemeister
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Kristine
authors.initials: K
authors.lastname: Broglio
authors.forename: Barry
authors.initials: B
authors.lastname: Samuels
authors.forename: Frederic
authors.initials: F
authors.lastname: Gilles
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Sarris
authors.forename: Susan
authors.initials: S
authors.lastname: Hart
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trehu
authors.forename: David
authors.initials: D
authors.lastname: Schenkein
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabanillas
authors.forename: Alma M
authors.initials: AM
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib