Abstract | PURPOSE: PATIENTS AND METHODS: Patients were treated with O(6)-BG at an intravenous dose of 120 mg/m(2) followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week intervals. RESULTS: Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hematopoietic toxicity. Twelve patients experienced reversible > or = grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/- 1.7 microg/mL/h v 5.0 +/- 1.3 microg/mL/h) of O(6)-BG for patients receiving phenytoin and those not treated with this drug. CONCLUSION: These results indicate that O(6)-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection.
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Authors | Jennifer A Quinn, James Pluda, M Eileen Dolan, Shannon Delaney, Richard Kaplan, Jeremy N Rich, Allan H Friedman, David A Reardon, John H Sampson, O Michael Colvin, Michael M Haglund, Anthony E Pegg, Robert C Moschel, Roger E McLendon, James M Provenzale, Sridharan Gururangan, Sandra Tourt-Uhlig, James E Herndon 2nd, Darell D Bigner, Henry S Friedman |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 20
Issue 9
Pg. 2277-83
(May 01 2002)
ISSN: 0732-183X [Print] United States |
PMID | 11980998
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Nitrosourea Compounds
- O(6)-benzylguanine
- Guanine
- Carmustine
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Area Under Curve
- Brain Neoplasms
(drug therapy)
- Carmustine
(administration & dosage, pharmacokinetics)
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Drug Resistance, Neoplasm
- Female
- Glioma
(drug therapy)
- Guanine
(administration & dosage, analogs & derivatives, pharmacokinetics)
- Humans
- Male
- Middle Aged
- Nitrosourea Compounds
(pharmacology)
- Treatment Outcome
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