AUTHOR=Qaddoumi Ibrahim , Kocak Mehmet , Pai-Panandiker Atmaram S., Armstrong Gregory T., Wetmore Cynthia , Crawford John R., Lin Tong , Boyett James M., Kun Larry E., Boop Fredrick A., Merchant Thomas E., Ellison David W., Gajjar Amar , Broniscer Alberto 

TITLE=Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas

JOURNAL=Frontiers in Oncology

VOLUME=4

YEAR=2014

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00067

DOI=10.3389/fonc.2014.00067

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Epidermal growth factor receptor is overexpressed in most pediatric high-grade 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.</p><p><bold>Methods:</bold> 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<sup>2</sup> 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).</p><p><bold>Results:</bold> 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 (<italic>n</italic> = 11), dermatologic (<italic>n</italic> = 5), and metabolic (<italic>n</italic> = 4). One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis.</p><p><bold>Conclusion:</bold> 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.</p>