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Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas. 2014

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

Department of Oncology, St. Jude Children's Research Hospital , Memphis, TN , USA ; Department of Pediatrics, University of Tennessee Health Sciences Center , Memphis, TN , USA.

BACKGROUND 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. 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. CONCLUSIONS 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.