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Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas.

Publication ,  Journal Article
Herndon, J; Vredenburgh, J; Reardon, D; Desjardins, A; Peters, K; Gururangan, S; Norfleet, J; Friedman, A; Bigner, D; Friedman, HS
Published in: J Clin Oncol
May 20, 2009

e13016 Background: Recurrent malignant gliomas have a poor prognosis, with a median survival of 6-15 months, with grade 4 glioblastomas more aggressive than grade 3 anaplastic astrocytomas or oligodendrogliomas. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) are critically important in glioma biology. Vandetanib is a multi-kinase inhibitor, predominantly of VEGF and EGF. We report a phase I trial of vandetanib in combination with oral etoposide for recurrent malignant glioma. METHODS: Patients with histologically documented recurrent grade 3 or grade 4 malignant glioma were eligible. Patients were treated with daily oral vandetanib and oral etoposide. The trial design was a modified 3 + 3 Phase I design, with the dose levels outlined below. RESULTS: Eighteen patients have been accrued. There was more hematologic toxicity than expected, with 3/6 of the patients enrolled at dose level 1 developing grade 4 neutropenia. There were no DLT's at the -1 dose level. The protocol was amended to decrease the dose of etoposide to 50 mg daily for 21 days, then 7 days off and dose escalation of vandetanib started again at 100 mg daily. Six patients had no dose limiting toxicity at the new dose level 1 of vandetanib 100 mg daily and etoposide 50 mg daily. Dose escalation continues. There has been clinical activity, with patients remaining stable on study for multiple cycles. CONCLUSIONS: Vandetanib and oral etoposide appear to interact to produce more marrow toxicity than expected. A phase II trial is planned when the MTD of vandetanib with reduced dose etoposide is determined. [Table: see text] No significant financial relationships to disclose.

Duke Scholars

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

e13016

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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ICMJE
MLA
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Herndon, J., Vredenburgh, J., Reardon, D., Desjardins, A., Peters, K., Gururangan, S., … Friedman, H. S. (2009). Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas. J Clin Oncol, 27(15_suppl), e13016.
Herndon, J., J. Vredenburgh, D. Reardon, A. Desjardins, K. Peters, S. Gururangan, J. Norfleet, A. Friedman, D. Bigner, and H. S. Friedman. “Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas.J Clin Oncol 27, no. 15_suppl (May 20, 2009): e13016.
Herndon J, Vredenburgh J, Reardon D, Desjardins A, Peters K, Gururangan S, et al. Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas. J Clin Oncol. 2009 May 20;27(15_suppl):e13016.
Herndon, J., et al. “Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas.J Clin Oncol, vol. 27, no. 15_suppl, May 2009, p. e13016.
Herndon J, Vredenburgh J, Reardon D, Desjardins A, Peters K, Gururangan S, Norfleet J, Friedman A, Bigner D, Friedman HS. Phase I trial of vendetanib and oral etoposide for recurrent malignant gliomas. J Clin Oncol. 2009 May 20;27(15_suppl):e13016.

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

e13016

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences