Originally published as JCO Early Release 10.1200/JCO.2008.18.8417 on February 9 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quinn, J. A. Articles by Friedman, H. S. Search for Related Content PubMed PubMed Citation Articles by Quinn, J. A. Articles by Friedman, H. S. Social Bookmarking                            What's this?

Phase II Trial of Temozolomide Plus O⁶-Benzylguanine in Adults With Recurrent, Temozolomide-Resistant Malignant Glioma

From the Departments of Surgery, Pathology, Biostatistics, and Bioinformatics, Duke University Medical Center, Durham, NC.

Corresponding author: Henry S. Friedman, MD, Duke University Medical Center, PO Box 3624, Durham, NC 27710; e-mail: fried003{at}mc.duke.edu.

Purpose This phase II trial was designed to define the role of O⁶-benzylguanine (O⁶-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O⁶-BG in combination with temozolomide.

Patients and Methods Patients were accrued into two independent strata on the basis of histology: glioblastoma multiforme (GBM) and anaplastic glioma. Both temozolomide and O⁶-BG were administered on day 1 of a 28-day treatment cycle. Patients were administered a 1-hour O⁶-BG infusion at a dose of 120 mg/m² followed immediately by a 48-hour infusion at a dose of 30 mg/m²/d. Temozolomide was administered orally within 60 minutes of the end of the 1-hour O⁶-BG infusion at a dose of 472 mg/m². The primary end point was objective response rate. Secondary end points included progression-free survival, overall survival, and safety.

Results Sixty-six of 67 patients who enrolled were treated with temozolomide and O⁶-BG. One of 34 patients (3%) with GBM (95% CI, 0.1% to 15%) and five of 32 assessable patients (16%) with anaplastic glioma (95% CI, 5% to 33%) were responders. The most commonly reported adverse events were grade 4 hematologic events experienced in 48% of the patients.

Conclusion O⁶-BG when added to a 1-day dosing regimen of temozolomide was able to restore temozolomide sensitivity in patients with temozolomide-resistant anaplastic glioma, but there seemed to be no significant restoration of temozolomide sensitivity in patients with temozolomide-resistant GBM.

Supported by National Institute of Neurological Disorders and Stroke Grant No. 5P50 NS20023-25, National Institutes of Health (NIH) Specialized Program of Research Excellence Grant No. 5P50 CA 108786-4, NIH Merit Award R37 CA 011898-38, and NIH Grant No. 1 R21 CA 101298-01; S.X.J. was supported by NIH Grant No. TL1 RR024126.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00613093 [ClinicalTrials.gov] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. E. Hegi, D. Sciuscio, A. Murat, M. Levivier, and R. Stupp Epigenetic Deregulation of DNA Repair and Its Potential for Therapy Clin. Cancer Res., August 15, 2009; 15(16): 5026 - 5031. [Abstract] [Full Text] [PDF]