title: Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma.
abstract: OBJECTIVE
  To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL).
  
  
  METHODS
  Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least 1 month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/microL (500/microL if documented bone marrow involvement); and platelet count more than 50,000/microL.
  
  
  RESULTS
  Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SLL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7).
  
  
  CONCLUSIONS
  These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL.
authors.affiliation: Department of Medicine, Lymphoma and Developmental Chemotherapy Services, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. oconnoro@mskcc.org
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Craig
authors.initials: C
authors.lastname: Moskowitz
authors.forename: Jamie
authors.initials: J
authors.lastname: Muzzy
authors.forename: Barbara
authors.initials: B
authors.lastname: MacGregor-Cortelli
authors.forename: Michael
authors.initials: M
authors.lastname: Stubblefield
authors.forename: David
authors.initials: D
authors.lastname: Straus
authors.forename: Carol
authors.initials: C
authors.lastname: Portlock
authors.forename: Paul
authors.initials: P
authors.lastname: Hamlin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Choi
authors.forename: Otila
authors.initials: O
authors.lastname: Dumetrescu
authors.forename: Dixie
authors.initials: D
authors.lastname: Esseltine
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trehu
authors.forename: Julian
authors.initials: J
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: Schenkein
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib