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

ABSTRACT: 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. 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.

SUBMITTER: Qaddoumi I 

PROVIDER: S-EPMC3978340 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature