Details

Autor(en) / Beteiligte

• Aregawi, D.
• Kreisl, T. N.
• Innis, E.
• Fine, H. A.

Titel

AT-06 A PHASE II TRIAL OF TAMOXIFEN AND BORTEZOMIB IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

Ist Teil von

• Neuro-oncology (Charlottesville, Va.), 2014-11, Vol.16 (suppl 5), p.v9-v9

Erscheinungsjahr

2014

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• BACKGROUND: Preclinical studies indicated that inhibition of NF-kB with bortezemib markedly enhance tamoxifen-mediated glioma apoptosis. A potentially synergistic cytotoxic effect of the combination may benefit patients with malignant gliomas. METHODS: We conducted single institution phase II trial to evaluate efficacy and safety of high dose tamoxifen with bortezomib in adults with recurrent high-grade glioma (HGG). Primary endpoint was radiographic response. Exclusion criteria included concurrent enzyme inducing anticonvulsants and grade greater than or equal to 2 peripheral neuropathy. Patients received tamoxifen (120 mg PO twice daily) and bortezomib (1.3 mg /m2 of IV on days 3, 6, 10, 13, 24, 27, 31, and 34) of every 6 week cycle. Contrast-enhanced MRI was obtained at the end of each cycle. RESULTS: 42 patients are included in this analysis; 12 anaplastic glioma (AG), 30 glioblastoma (GBM), 32 males, and 10 females. Median age was 39 years (range 28-65) for AG, and 48 years (range 19-68) for GBM. Median KPS at entry was 90 for AG (range 70-100) and 80 for GBM (range 60-100). Median number of prior therapies were 3 (range 1-7). Grade greater than or equal to 3 treatment related toxicities included lymphopenia (4 pts), hypophosphatemia (3 pts), thromobocytopenia (2 pts), and one instance each of hyponatremia, headache, dyspnea, and DVT. One GBM patient withdrew, two were removed for toxicity, and all others had progression. Among 40 patients evaluable for response, only one achieved stable disease unsustained beyond the first response assessment; all others had rapid progression. Median progression free survival was 5.9 and 5.7 weeks while median overall survival was 25.6 and 14.7 weeks for AG and GBM respectively. The study was closed early due to poor enrollment and therapeutic futility. CONCLUSION: Combination tamoxifen and bortezomib has no activity in this cohort of recurrent HGG. Poor results were likely influenced by poor penetration of bortezomib across blood brain barrier.