Journal of Clinical Oncology, Vol 21, Issue 12
(June), 2003: 2299-2304
© 2003 American Society for Clinical Oncology
Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas
Howard A. Fine,
Patrick Y. Wen,
Elizabeth A. Maher,
Elene Viscosi,
Tracy Batchelor,
Nehal Lakhani,
William D. Figg,
Benjamin W. Purow,
Craig B. Borkowf
From the Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurologic Disorder and Stroke, and Cancer Therapeutics Branch and the Cancer Prevention Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and Center for Neuro-Oncology, Dana-Farber Cancer Institute, Department of Neurology the Brigham and Women’s Hospital, and the Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Address reprint requests to Howard A. Fine, MD, Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, MSC 1911, Building 10, Room 12S245, Bethesda, MD 20892-1911; email: hfine{at}mail.nih.gov.
Purpose: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas.
Patients and Methods: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated.
Results: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls.
Conclusion: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.
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