Artikel
Bevacizumab and Irinotecan therapy in recurrent malignant glioma, is it really effective?
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Despite extensive treatment with alkylating chemotherapy, most patients with malignant gliomas suffer from a recurrence within 12 months. We therefore decided to treat extensively pre-treated patients upon recurrence with Bevacizumab (B), an antibody against VEGF, and Irinotecan (I), a topoisomerase I inhibitor. We also performed early MRI and FET-PET studies after treatment with Bevacizumab and Irinotecan to elicit any immediate early effect on the blood brain barrier. Effects on OAS and PFS of this therapy were evaluated.
Methods: 29 patients with recurrent malignant gliomas [20 GBM (WHO°IV), 6 anaplastic astrocytomas (WHO°III) and 3 secondary GBM (WHO°IV)] were included in this retrospective analysis. All patients have been previously treated with radiation and chemotherapy (Stupp) with a median pre-treatment TMZ cycle count of 10. 18 patients received Gliadel Implantation as second line therapy. 12 patients received B/I as second line therapy, 13 patients as third and 4 patients as fourth line therapy. The median observation time was 24 months (11–37). Patients were treated every second week with 10 mg/kg (B) and 125 mg/m2 (I) in a six weeks cycle. The median number of cycles was 2 (1–9). 14 patients were followed by MRI and FET-PET, 15 patients underwent MRI studies only. Two patients underwent FET-PET scans 3 and 5 days after the first therapy.
Results: All 14 patients evaluated with FET-PET showed less tracer uptake on first FET-PET imaging. In two cases there was an extremely early response in terms of reduced enhancement in FET-PET scans, 3 and 5 days after first therapy. MRI obtained at 1 month follow-up showed tumor progression in 7 patients and stable disease in 4 patients. Median PFS was 18 weeks for all patients. 19 patients showed multifocal progression in MRI. For patients with GBM, AA and sec. GBM a PFS of 15 weeks, 18 weeks and 51 weeks was noticed. The complete OAS was 30 months from initial diagnosis until death. The median OAS was 7 months after initiating therapy with B/I.
Conclusions: The immediate early response in FET-PET and MRI may indicate a direct effect on vascular permeability rather than true remission. However, the median PFS of 18 weeks, as well as the OAS of 7 months suggests that treatment with B/I might have some effect in this extensively pre-treated population