A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas

A report from the Pediatric Brain Tumor Consortium

Ian F. Pollack, Clinton F. Stewart, Mehmet Kocak, Tina Young Poussaint, Alberto Broniscer, Anu Banerjee, James G. Douglas, Larry E. Kun, James M. Boyett, J. Russell Geyer

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

This phase II study was designed to assess the safety and efficacy of gefitinib given with and following radiation therapy in children newly diagnosed with a poor prognosis brainstem glioma. Eligible patients were those with a previously untreated nondisseminated diffuse intrinsic brainstem glioma. Histological confirmation was not required, provided patients had a characteristic clinical history and MRI findings. Treatment consisted of gefitinib, administered orally, 250 mg/m2/day, during standard external beam radiotherapy, continuing for up to 13 monthly courses in the absence of disease progression or unacceptable toxicity. Toxicities, particularly intratumoral hemorrhage, were monitored. Pharmacokinetics and investigational imaging studies were performed in consenting patients. Forty-three eligible patients were included in the study. Therapy was well tolerated; only 4 patientswerewithdrawn from the study for dose-limiting toxicity after receiving therapy for 6, 9, 17, and 24 weeks. The 12- and 24-month progression-free survival rates were 20.9±5.6 % and 9.3±4%, respectively. Overall survival rates were 56.4±7.6% and 19.6± 5.9%, respectively, which appear nominally superior to other contemporaneous Pediatric Brain Tumor Consortium trials. Three patients remain progressionfree survivors with ≥ 36 months follow-up. The observation that a subset of children with this generally fatal tumor experienced long-term progression-free survival, coupled with recent observations regarding the molecular features of brainstem gliomas, raises the possibility that prospective molecular characterization may allow enrichment of treatment responders and improvement in outcome results in future studies of biologically targeted agents.

Original languageEnglish (US)
Pages (from-to)290-297
Number of pages8
JournalNeuro-Oncology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Brain Neoplasms
Glioma
Brain Stem
Pediatrics
Disease-Free Survival
Radiotherapy
Survival Rate
Therapeutics
Survivors
Disease Progression
Pharmacokinetics
gefitinib
Hemorrhage
Safety
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas : A report from the Pediatric Brain Tumor Consortium. / Pollack, Ian F.; Stewart, Clinton F.; Kocak, Mehmet; Poussaint, Tina Young; Broniscer, Alberto; Banerjee, Anu; Douglas, James G.; Kun, Larry E.; Boyett, James M.; Geyer, J. Russell.

In: Neuro-Oncology, Vol. 13, No. 3, 01.03.2011, p. 290-297.

Research output: Contribution to journalArticle

Pollack, IF, Stewart, CF, Kocak, M, Poussaint, TY, Broniscer, A, Banerjee, A, Douglas, JG, Kun, LE, Boyett, JM & Geyer, JR 2011, 'A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas: A report from the Pediatric Brain Tumor Consortium', Neuro-Oncology, vol. 13, no. 3, pp. 290-297. https://doi.org/10.1093/neuonc/noq199
Pollack, Ian F. ; Stewart, Clinton F. ; Kocak, Mehmet ; Poussaint, Tina Young ; Broniscer, Alberto ; Banerjee, Anu ; Douglas, James G. ; Kun, Larry E. ; Boyett, James M. ; Geyer, J. Russell. / A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas : A report from the Pediatric Brain Tumor Consortium. In: Neuro-Oncology. 2011 ; Vol. 13, No. 3. pp. 290-297.
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