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Erschienen in: Journal of Neuro-Oncology 2/2010

01.01.2010 | Clinical Study - Patient Study

Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma

verfasst von: David A. Reardon, Annick Desjardins, James J. Vredenburgh, Sridharan Gururangan, Allan H. Friedman, James E. Herndon II, Jennifer Marcello, Julie A. Norfleet, Roger E. McLendon, John H. Sampson, Henry S. Friedman

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2010

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Abstract

We evaluated the anti-tumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) in a phase 2, open-label, single-arm trial. Thirty-two patients received daily erlotinib and sirolimus. The doses of erlotinib and sirolimus were 150 mg and 5 mg for patients not on concurrent CYP3A-inducing anti-epileptics (EIAEDS), and 450 mg and 10 mg for patients on EIAEDS. Evaluations were performed every two months. The primary endpoint was 6-month progression-free survival and secondary endpoints included safety and overall survival. Archival tumor samples were assessed for EGFR, EGFRvIII, PTEN, pAKT and pS6. Enrolled patients were heavily pre-treated including 53% who had received three or more prior chemotherapy agents and 28% who had received prior bevacizumab therapy. The most common grade ≥2 adverse events were rash (59%), mucositis (34%) and diarrhea (31%). Grade 3 or higher events were rare. Best radiographic response included stable disease in 15 patients (47%); no patients achieved either a CR or PR. The estimated 6-month progression-free survival was 3.1% for all patients. Progression-free survival was better for patients not on EIAEDs (P = 0.03). Tumor markers failed to show an association with PFS except for increased pAKT expression which achieved borderline significance (P = 0.045). Although neither rash nor diarrhea had an association with outcome, hyperlipidemia was associated with longer PFS (P = 0.029). Erlotinib plus sirolimus was well tolerated but had negligible activity among unselected recurrent GBM patients. (ClinicalTrials.gov number: NCT0062243).
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Metadaten
Titel
Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma
verfasst von
David A. Reardon
Annick Desjardins
James J. Vredenburgh
Sridharan Gururangan
Allan H. Friedman
James E. Herndon II
Jennifer Marcello
Julie A. Norfleet
Roger E. McLendon
John H. Sampson
Henry S. Friedman
Publikationsdatum
01.01.2010
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2010
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-009-9950-0

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