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


Authors: Raizer, J. J.; Abrey, L. E.; Lassman, A. B.; Chang, S. M.; Lamborn, K. R.; Kuhn, J. G.; Yung, W. K. A.; Gilbert, M. R.; Aldape, K. A.; Wen, P. Y.; Fine, H. A.; Mehta, M.; Deangelis, L. M.; Lieberman, F.; Cloughesy, T. F.; Robins, H. I.; Dancey, J.; Prados, M. D.
Article Title: A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy
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. © The Author(s) 2009.
Keywords: adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; treatment response; aged; disease-free survival; middle aged; unclassified drug; major clinical study; overall survival; clinical trial; fatigue; erlotinib; area under the curve; diarrhea; drug efficacy; drug safety; hypophosphatemia; monotherapy; side effect; antineoplastic agents; cancer radiotherapy; temozolomide; recurrent cancer; glioma; brain neoplasms; antineoplastic agent; progression free survival; controlled clinical trial; drug eruption; infection; multiple cycle treatment; phase 2 clinical trial; neoplasm recurrence, local; thrombocytopenia; dehydration; myalgia; epidermal growth factor receptor; weight reduction; abdominal pain; alanine aminotransferase blood level; hypomagnesemia; kaplan-meiers estimate; drug induced headache; hypokalemia; survival time; tissue distribution; blood sampling; glioblastoma; muscle weakness; therapy effect; seizure; maximum plasma concentration; time to maximum plasma concentration; meningioma; drug blood level; quinazolines; bilirubin blood level; pharmacokinetics; hypocalcemia; osi 420
Journal Title: Neuro-Oncology
Volume: 12
Issue: 1
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2010-01-01
Start Page: 95
End Page: 103
Language: English
DOI: 10.1093/neuonc/nop015
PUBMED: 20150372
PROVIDER: scopus
PMCID: PMC2940554
DOI/URL:
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 20 April 2011" - "CODEN: NEURJ" - "Source: Scopus"
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MSK Authors
  1. Andrew Lassman
    111 Lassman
  2. Lauren E Abrey
    276 Abrey