A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas

Jeffrey J. Raizer, Lauren E. Abrey, Andrew B. Lassman, Susan M. Chang, Kathleen R. Lamborn, John G. Kuhn, W. K.Alfred Yung, Mark R. Gilbert, Kenneth D. Aldape, Patrick Y. Wen, Howard A. Fine, Minesh Mehta, Lisa M. DeAngelis, Frank Lieberman, Timothy F. Cloughesy, H. Ian Robins, Janet Dancey, Michael D. Prados

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The objective of this phase I study was to determine the maximal tolerated dose (MTD) of erlotinib in patients with recurrent malignant gliomas (MGs) or recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose escalation was by a standard 3 x 3 design. The initial starting dose of erlotinib was 150 mg daily. If no dose-limiting toxicity (DLT) was observed, then dose escalation occurs as follows: 200 mg/day, 275 mg/day, and then increased in 125 mg increments until the MTD was reached. The MTD was defined as the dose where ≤1 of 6 patients experienced a DLT and the dose above had 2 or more DLTs. The MTD was 650 mg/day; the observed DLTs were grade 3 rash in 2 patients at 775 mg/day. Pharmacokinetic analysis showed a significant influence of EIAEDs on the metabolism of erlotinib when compared with our phase II data published separately. Primary toxicities were rash and diarrhea. The MTD of erlotinib in patients receiving EIAEDs is substantially higher than the standard dose of 150 mg. This has important implications for further development of this drug in the treatment of MG as well as the optimal management of patients with other malignancies such as NSCLC who are on enzyme-inducing drugs.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalNeuro-oncology
Volume12
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Erlotinib
  • Glioblastoma
  • Glioma
  • Meningioma
  • Pharmacokinetics

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas'. Together they form a unique fingerprint.

Cite this