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Neurology. 2008 Mar 4;70(10):779-
Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and
patterns of recurrence.
Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL,
Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY.
Department of Neurology, Dana-Farber/
Center and Harvard Medical School, SW430B, 44 Binney St., Boston, MA
02115, USA. anorden@partners.
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-
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.