Phase II study of bevacizumab and erlotinib in patients with recurrent glioblastoma multiforme

Sathornsumetee, Sith; Vredenburgh, James J.; Rich, Jeremy; Desjardins, Annick; Quinn, Jennifer A.; Mathe, Anaelle; Gururangan, Sridharan; Friedman, Allan H.; Friedman, Henry S.; Reardon, David A.

doi:10.1200/jco.2008.26.15_suppl.13008

Cited by 9 publications

(7 citation statements)

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“…The reported objective radiological ORs were approximately double the baseline rates after inhibition of EGFR using erlotinib or gefitinib in 6 of 12 evaluable single-inhibitor studies, in 2 of 7 studies combining inhibition of EGFR and mTOR, and in none of 4 evaluable studies combining EGFR inhibition with conventional therapy. In 1 study combining EGFR inhibition by erlotinib with VEGF inhibition by bevacizumab, an OR of 48% was observed, 16 which was comparable with the results for pan-VEGFR inhibition with cediranib. 17 The ORs after inhibition of mTOR were comparable with the baseline results in 4 single-agent studies.…”

Section: Radiological Responsesupporting

confidence: 56%

Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies

2010

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The efficacy of small-molecule kinase inhibitors has recently changed standard clinical practice for several solid cancers. Glioblastoma is a solid cancer that universally recurs and unrelentingly results in death despite maximal surgery and radiotherapy with concomitant and adjuvant temozolomide. Several clinical studies using kinase inhibitors in glioblastoma have been reported. The present study systematically reviews the efficacy, toxicity, and tissue analysis of small-molecule kinase inhibitors in adult patients with glioblastoma as reported in published clinical studies and determines which kinases have been targeted by the inhibitors used in these studies. Publications were retrieved using a MEDLINE search and by screening meeting abstracts. A total of 60 studies qualified for inclusion, of which 25 were original reports. A total of 2385 glioblastoma patients receiving kinase inhibitors could be evaluated. The study designs included 2 phase III studies and 37 phase II studies. Extracted data included radiological response, progression-free survival, overall survival, toxicity, and biomarker analysis. The main findings were that (i) efficacy of small-molecule kinase inhibitors in clinical studies with glioblastoma patients does not yet warrant a change in standard clinical practice and (ii) 6 main kinase targets for inhibitors have been evaluated in these studies: EGFR, mTOR, KDR, FLT1, PKCbeta, and PDGFR.

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Section: Radiological Responsesupporting

confidence: 56%

Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies

2010

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“…The combination of erlotinib and bevacizumab in patients with recurrent GBM was found to be safe and associated with promising efficacy (objective response rate of 48% and 6-month progression free survival of 24%). 109 A Phase I trial of erlotinib and the mammalian target of rapamycin (mTOR) inhibitor temsirolimus in patients with recurrent high-grade gliomas shows the combination to be safe. 110 …”

Section: Clinical Trials Of Egfr Therapeutic Agentsmentioning

confidence: 99%

The EGFRvIII variant in glioblastoma multiforme

Gan

Kaye

Luwor

2009

Journal of Clinical Neuroscience

337

253

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“…Unfortunately the results so far have not suggested any additional benefit over bevacizumab alone. 26–27 …”

Section: Antiangiogenic Agentsmentioning

confidence: 99%

Antiangiogenic Therapy for Glioblastoma

Gerstner¹,

Batchelor²

2012

The Cancer Journal

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Glioblastomas are among the most vascular tumors due to the expression of a variety of pro-angiogenic factors. New drug regimens are being developed to target angiogenesis in an attempt to arrest tumor growth. In particular, the vascular endothelial growth factor (VEGF) pathway has been a prime drug target. Preliminary results with anti-VEGF agents have been promising with prolonged progression-free survival reported. In addition, the anti-permeability effects of anti-VEGF agents have important consequences for tumor imaging and for patient quality of life by decreasing corticosteroid dependence. Unfortunately, the response to anti-VEGF therapy is transient and the majority of patients eventually relapse so more work is needed to understand mechanisms of tumor escape.

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Phase II study of bevacizumab and erlotinib in patients with recurrent glioblastoma multiforme

Cited by 9 publications

References 0 publications

Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies

Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies

The EGFRvIII variant in glioblastoma multiforme

Antiangiogenic Therapy for Glioblastoma

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