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

Publication ,  Journal Article
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Friedman, AH; Herndon, JE; Marcello, J; Norfleet, JA; McLendon, RE; Sampson, JH ...
Published in: J Neurooncol
January 2010

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 > or = 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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Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

January 2010

Volume

96

Issue

2

Start / End Page

219 / 230

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Sirolimus
  • Quinazolines
  • Protein Kinase Inhibitors
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Humans
 

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Reardon, D. A., Desjardins, A., Vredenburgh, J. J., Gururangan, S., Friedman, A. H., Herndon, J. E., … Friedman, H. S. (2010). Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol, 96(2), 219–230. https://doi.org/10.1007/s11060-009-9950-0
Reardon, David A., Annick Desjardins, James J. Vredenburgh, Sridharan Gururangan, Allan H. Friedman, James E. Herndon, Jennifer Marcello, et al. “Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma.J Neurooncol 96, no. 2 (January 2010): 219–30. https://doi.org/10.1007/s11060-009-9950-0.
Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Friedman AH, Herndon JE, et al. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol. 2010 Jan;96(2):219–30.
Reardon, David A., et al. “Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma.J Neurooncol, vol. 96, no. 2, Jan. 2010, pp. 219–30. Pubmed, doi:10.1007/s11060-009-9950-0.
Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Friedman AH, Herndon JE, Marcello J, Norfleet JA, McLendon RE, Sampson JH, Friedman HS. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol. 2010 Jan;96(2):219–230.
Journal cover image

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

January 2010

Volume

96

Issue

2

Start / End Page

219 / 230

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Sirolimus
  • Quinazolines
  • Protein Kinase Inhibitors
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Humans