Phase II trial of erlotinib during and after radiotherapy in children with newly diagnosed high-grade gliomas

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

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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/m2 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.

Original languageEnglish (US)
Article numberArticle 67
JournalFrontiers in Oncology
Volume4 APR
DOIs
StatePublished - Jan 1 2014

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Glioma
Astrocytoma
Radiotherapy
Glioblastoma
Disease-Free Survival
Neoplasms
Neuroepithelial Neoplasms
Erlotinib Hydrochloride
Septic Shock
Epidermal Growth Factor Receptor
Pancreatitis
Adrenal Cortex Hormones
Pediatrics
Brain
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Phase II trial of erlotinib during and after radiotherapy in children with newly diagnosed high-grade gliomas. / Qaddoumi, Ibrahim; Kocak, Mehmet; Pai Panandiker, Atmaram S.; Armstrong, Gregory; Wetmore, Cynthia; Crawford, John R.; Lin, Tong; Boyett, James M.; Kun, Larry E.; Boop, Frederick; Merchant, Thomas E.; Ellison, David W.; Gajjar, Amar; Broniscer, Alberto.

In: Frontiers in Oncology, Vol. 4 APR, Article 67, 01.01.2014.

Research output: Contribution to journalArticle

Qaddoumi, I, Kocak, M, Pai Panandiker, AS, Armstrong, G, Wetmore, C, Crawford, JR, Lin, T, Boyett, JM, Kun, LE, Boop, F, Merchant, TE, Ellison, DW, Gajjar, A & Broniscer, A 2014, 'Phase II trial of erlotinib during and after radiotherapy in children with newly diagnosed high-grade gliomas', Frontiers in Oncology, vol. 4 APR, Article 67. https://doi.org/10.3389/fonc.2014.00067
Qaddoumi, Ibrahim ; Kocak, Mehmet ; Pai Panandiker, Atmaram S. ; Armstrong, Gregory ; Wetmore, Cynthia ; Crawford, John R. ; Lin, Tong ; Boyett, James M. ; Kun, Larry E. ; Boop, Frederick ; Merchant, Thomas E. ; Ellison, David W. ; Gajjar, Amar ; Broniscer, Alberto. / Phase II trial of erlotinib during and after radiotherapy in children with newly diagnosed high-grade gliomas. In: Frontiers in Oncology. 2014 ; Vol. 4 APR.
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T1 - Phase II trial of erlotinib during and after radiotherapy in children with newly diagnosed high-grade gliomas

AU - Qaddoumi, Ibrahim

AU - Kocak, Mehmet

AU - Pai Panandiker, Atmaram S.

AU - Armstrong, Gregory

AU - Wetmore, Cynthia

AU - Crawford, John R.

AU - Lin, Tong

AU - Boyett, James M.

AU - Kun, Larry E.

AU - Boop, Frederick

AU - Merchant, Thomas E.

AU - Ellison, David W.

AU - Gajjar, Amar

AU - Broniscer, Alberto

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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/m2 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.

AB - 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/m2 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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