O6-benzylguanine and BCNU in multiple myeloma: a phase II trial.

Abstract

PURPOSE:

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: Eric D Batts, Christopher Maisel, Donna Kane, Lili Liu, Pingfu Fu, Timothy O'Brien, Scot Remick, Nizar Bahlis, Stanton L Gerson
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 60 Issue 3 Pg. 415-21 (Aug 2007) ISSN: 0344-5704 [Print] Germany
• PMID: 17354015 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• O(6)-benzylguanine
• Guanine
• DNA
• Carmustine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use, toxicity)
• Carmustine (administration & dosage, therapeutic use, toxicity)
• DNA (blood)
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Guanine (administration & dosage, analogs & derivatives, therapeutic use, toxicity)
• Humans
• Male
• Middle Aged
• Multiple Myeloma (drug therapy)
• Patient Selection
• Reference Values