Journal
FRONTIERS IN ONCOLOGY
Volume 4, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2014.00067
Keywords
erlotinib; epidermal growth factor receptor; high-grade glioma; pediatric; phase II; radiotherapy
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Funding
- National Institutes of Health Cancer Center Support (Core) [P30 CA021765]
- OSI Pharmaceuticals Inc.
- Genentech Inc.
- American Lebanese Syrian Associated Charities (ALSAC)
- NATIONAL CANCER INSTITUTE [P30CA021765, P01CA096832] Funding Source: NIH RePORTER
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Background: Epidermal growth factor receptor is overexpressed in most pediatric highgrade gliomas (HGG). Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy (RT) in children with newly diagnosed HGG. Methods: Following maximum surgical resection, patients between 3 and 21 years with non-metastatic HGG received local RT at 59.4 Gy (54 Gy for spinal tumors and those with >= 70% brain involvement). Erlotinib started on day 1 of RT (120 mg/m(2) per day) and continued for 2-years unless there was tumor progression or intolerable toxicities. The 2 year progression-free survival (PFS) was estimated for patients with intracranial anaplastic astrocytoma (AA) and glioblastoma (GBM). Results: Median age at diagnosis for 41 patients with intracranial tumors (21 with GBM and 20 with AA) was 10.9 years (range, 3.3-19 years). The 2-year PFS for patients with AA and GBM was 15 +/- 7 and 19 +/- 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n = 11), dermatologic (n = 5), and metabolic (n = 4). One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis. Conclusion: Although therapy with erlotinib was mostly well-tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and GBM.
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