Skip to main content
Journal cover image

Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma.

Publication ,  Journal Article
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, K; Gururangan, S; Sampson, JH; Marcello, J; Herndon, JE; McLendon, RE; Janney, D ...
Published in: J Neurooncol
January 2011

Sorafenib, an oral VEGFR-2, Raf, PDGFR, c-KIT and Flt-3 inhibitor, is active against renal cell and hepatocellular carcinomas, and has recently demonstrated promising activity for lung and breast cancers. In addition, various protracted temozolomide dosing schedules have been evaluated as a strategy to further enhance its anti-tumor activity. We reasoned that sorafenib and protracted, daily temozolomide may provide complementary therapeutic benefit, and therefore performed a phase 2 trial among recurrent glioblastoma patients. Adult glioblastoma patients at any recurrence after standard temozolomide chemoradiotherapy received sorafenib (400 mg twice daily) and continuous daily temozolomide (50 mg/m²/day). Assessments were performed every eight weeks. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary end points were radiographic response, overall survival (OS), safety and sorafenib pharmacokinetics. Of 32 enrolled patients, 12 (38%) were on CYP3-A inducing anti-epileptics (EIAEDs), 17 (53%) had 2 or more prior progressions, 15 had progressed while receiving 5-day temozolomide, and 12 (38%) had failed either prior bevacizumab or VEGFR inhibitor therapy. The most common grade ≥ 3 toxicities were palmer-planter erythrodysesthesia (19%) and elevated amylase/lipase (13%). Sorafenib pharmacokinetic exposures were comparable on day 1 regardless of EIAED status, but significantly lower on day 28 for patients on EIAEDs (P = 0.0431). With a median follow-up of 93 weeks, PFS-6 was 9.4%. Only one patient (3%) achieved a partial response. In conclusion, sorafenib can be safely administered with daily temozolomide, but this regimen has limited activity for recurrent GBM. Co-administration of EIAEDs can lower sorafenib exposures in this population.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

January 2011

Volume

101

Issue

1

Start / End Page

57 / 66

Location

United States

Related Subject Headings

  • Temozolomide
  • Sorafenib
  • Recurrence
  • Pyridines
  • Phenylurea Compounds
  • Oncology & Carcinogenesis
  • Niacinamide
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reardon, D. A., Vredenburgh, J. J., Desjardins, A., Peters, K., Gururangan, S., Sampson, J. H., … Friedman, H. S. (2011). Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol, 101(1), 57–66. https://doi.org/10.1007/s11060-010-0217-6
Reardon, David A., James J. Vredenburgh, Annick Desjardins, Katherine Peters, Sridharan Gururangan, John H. Sampson, Jennifer Marcello, et al. “Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma.J Neurooncol 101, no. 1 (January 2011): 57–66. https://doi.org/10.1007/s11060-010-0217-6.
Reardon DA, Vredenburgh JJ, Desjardins A, Peters K, Gururangan S, Sampson JH, et al. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol. 2011 Jan;101(1):57–66.
Reardon, David A., et al. “Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma.J Neurooncol, vol. 101, no. 1, Jan. 2011, pp. 57–66. Pubmed, doi:10.1007/s11060-010-0217-6.
Reardon DA, Vredenburgh JJ, Desjardins A, Peters K, Gururangan S, Sampson JH, Marcello J, Herndon JE, McLendon RE, Janney D, Friedman AH, Bigner DD, Friedman HS. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol. 2011 Jan;101(1):57–66.
Journal cover image

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

January 2011

Volume

101

Issue

1

Start / End Page

57 / 66

Location

United States

Related Subject Headings

  • Temozolomide
  • Sorafenib
  • Recurrence
  • Pyridines
  • Phenylurea Compounds
  • Oncology & Carcinogenesis
  • Niacinamide
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male