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

doi:10.1093/neuonc/nop017

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

Neurology

Research output: Contribution to journal › Article › peer-review

41 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 language	English (US)
Pages (from-to)	87-94
Number of pages	8
Journal	Neuro-oncology
Volume	12
Issue number	1
DOIs	https://doi.org/10.1093/neuonc/nop017
State	Published - Jan 2010

Keywords

Erlotinib
Glioblastoma
Glioma
Meningioma
Pharmacokinetics

ASJC Scopus subject areas

Oncology
Clinical Neurology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/neuonc/nop017

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Raizer, J. J., Abrey, L. E., Lassman, A. B., Chang, S. M., Lamborn, K. R., Kuhn, J. G., Yung, W. K. A., Gilbert, M. R., Aldape, K. D., Wen, P. Y., Fine, H. A., Mehta, M., DeAngelis, L. M., Lieberman, F., Cloughesy, T. F., Robins, H. I., Dancey, J., & Prados, M. D. (2010). A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas. Neuro-oncology, 12(1), 87-94. https://doi.org/10.1093/neuonc/nop017

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

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.",

keywords = "Erlotinib, Glioblastoma, Glioma, Meningioma, Pharmacokinetics",

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

year = "2010",

month = jan,

doi = "10.1093/neuonc/nop017",

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Raizer, JJ, Abrey, LE, Lassman, AB, Chang, SM, Lamborn, KR, Kuhn, JG, Yung, WKA, Gilbert, MR, Aldape, KD, Wen, PY, Fine, HA, Mehta, M, DeAngelis, LM, Lieberman, F, Cloughesy, TF, Robins, HI, Dancey, J & Prados, MD 2010, 'A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas', Neuro-oncology, vol. 12, no. 1, pp. 87-94. https://doi.org/10.1093/neuonc/nop017

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AU - Chang, Susan M.

AU - Lamborn, Kathleen R.

AU - Kuhn, John G.

AU - Yung, W. K.Alfred

AU - Gilbert, Mark R.

AU - Aldape, Kenneth D.

AU - Wen, Patrick Y.

AU - Fine, Howard A.

AU - Mehta, Minesh

AU - DeAngelis, Lisa M.

AU - Lieberman, Frank

AU - Cloughesy, Timothy F.

AU - Robins, H. Ian

AU - Dancey, Janet

AU - Prados, Michael D.

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KW - Meningioma

KW - Pharmacokinetics

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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