A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy

Jeffrey J. Raizer, Lauren E. Abrey, Andrew B. Lassman, Susan M. Chang, Kathleen R. Lamborn, John G. Kuhn, W. K.Alfred Yung, Mark R. Gilbert, Kenneth A. Aldape, Patrick Y. Wen, Howard A. Fine, Minesh Mehta, Lisa M. DeAngelis, Frank Lieberman, Timothy F. Cloughesy, H. Ian Robins, Janet Dancey, Michael D. Prados

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

Patients with (a) recurrent malignant glioma (MG): glioblastoma (GBM) or recurrent anaplastic glioma (AG), and (b) nonprogressive (NP) GBM following radiation therapy (RT) were eligible. Primary objective for recurrent MG was progression-free survival at 6 months (PFS-6) and overall survival at 12 months for NP GBM post-RT. Secondary objectives for recurrent MGs were response, survival, assessment of toxicity, and pharmacokinetics (PKs). Treatment with enzymeinducing antiepileptic drugs was not allowed. Patients received 150 mg/day erlotinib. Patients requiring surgery were treated 7 days prior to tumor removal for PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) and intracellular signaling pathways. Ninety-six patients were evaluable (53 recurrent MG and 43 NP GBM); 5 patients were not evaluable for response. PFS-6 in recurrent GBM was 3% with a median PFS of 2 months; PFS-6 in recurrent AG was 27% with a median PFS of 2 months. Twelvemonth survival was 57% in NP GBMs post-RT. Primary toxicity was dermatologic. The tissue-toplasma ratio normalized to nanograms per gram dry weight for erlotinib and OSI-420 ranged from 25% to 44% and 30% to 59%, respectively, for pretreated surgical patients. No effect on EGFR or intratumoral signaling was seen. Patients with NP GBM post-RT who developed rash in cycle 1 had improved survival (P < .001). Single-agent activity of erlotinib is minimal for recurrent MGs and marginally beneficial following RT for NP GBM patients. Development of rash in cycle 1 correlates with survival in patients with NP GBM after RT.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalNeuro-oncology
Volume12
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Erlotinib
  • Glioblastoma
  • Glioma
  • Meningioma
  • Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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