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From the Division of Cancer Neurology (A.D.N., A.S.C., L.G.E., B.L., J.D., S.K., P.Y.W.), Department of Neurology, Brigham and Women's Hospital and Center For Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School; Brigham and Women's Hospital Department of Radiology and Harvard Medical School (G.S.Y., K.S., R.K., G.L.R.); and Massachusetts General Hospital Biostatistics Center (A.M.), Boston.
Address correspondence and reprint requests to Dr Norden, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, SW430B, 44 Binney St., Boston, MA 02115 anorden{at}partners.org
Background: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor.
Methods: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone.
Results: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders.
Conclusions: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth.
Abbreviations: AA = anaplastic astrocytoma; AG = anaplastic glioma; CR = complete response; GBM = glioblastoma; EIAED = enzyme-inducing antiepileptic drug; FLAIR = fluid-attenuated inversion recovery; KPS = Karnofsky Performance Status; MR = minimal response; PFS = progression-free survival; PR = partial response; rFPR = relative FLAIR progression ratio; rNTR = relative nonenhancing tumor ratio; T1W = T1-weighted; VEGF = vascular endothelial growth factor.
*These authors contributed equally to this work.
Supported by the Amos E. Wasgatt Brain Tumor Research Fund.
Disclosure: P.Y. Wen receives research support from Genentech, Inc. The other authors report no conflicts of interest.
Received July 2, 2007. Accepted in final form September 18, 2007.
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