title: O6-benzylguanine and BCNU in multiple myeloma: a phase II trial.
abstract: OBJECTIVE
  Carmustine (BCNU) is known to have modest activity in multiple myeloma; however, resistance to BCNU manifests by the activity of O6-methylguanine methyltransferase (MGMT). The objective of this study was to determine the safety and efficacy of depletion of MGMT activity in plasma cells using O6-benzylguanine (O6-BG) with BCNU in patients with multiple myeloma.
  
  
  METHODS
  Patients with previously treated or untreated multiple myeloma were eligible. Cycles of O6-BG at a dose of 120 mg/m2 and BCNU at a dose of 40 mg/m2 were repeated every 6 weeks.
  
  
  RESULTS
  Seventeen patients were enrolled on the study, with a median follow-up of 24.5 (range 5-69) months. One complete response (7%) and 3 partial responses (20%) were observed. Nine patients (60%) had stable disease. Bone marrow studies demonstrated 94% depletion of MGMT activity in CD38+ marrow cells. The most frequent grade 3 and 4 adverse events were neutropenia (71%), lymphocytopenia (53%), and thrombocytopenia (53%).
  
  
  CONCLUSIONS
  Chemotherapy utilizing the MGMT inhibitor O6-benzylguanine and BCNU results in inhibition of MGMT activity in malignant plasma cells and produces meaningful responses in a modest proportion of patients with multiple myeloma. Hematologic toxicity with this regimen is significant and dose-limiting.
authors.affiliation: Developmental Therapeutics Program, CASE Comprehensive Cancer Center and the Division of Hematology/Oncology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Batts
authors.forename: Christopher
authors.initials: C
authors.lastname: Maisel
authors.forename: Donna
authors.initials: D
authors.lastname: Kane
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.forename: Scot
authors.initials: S
authors.lastname: Remick
authors.forename: Nizar
authors.initials: N
authors.lastname: Bahlis
authors.forename: Stanton L
authors.initials: SL
authors.lastname: Gerson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002330:Carmustine / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D004247:DNA / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D018579:Patient Selection; D012016:Reference Values
chemical_list: C064976:O(6)-benzylguanine; D006147:Guanine; D004247:DNA; D002330:Carmustine