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

Authors: 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.; De Angelis, L. M.; Lieberman, F.; Cloughesy, T. F.; Robins, H. I.; Dancey, J.; Prados, M. D.
Article 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. © The Author(s) 2009.
Keywords: adult; cancer chemotherapy; clinical article; aged; middle aged; young adult; unclassified drug; clinical trial; fatigue; erlotinib; area under the curve; diarrhea; hypophosphatemia; side effect; antineoplastic agents; cancer radiotherapy; recurrent cancer; glioma; brain neoplasms; antineoplastic agent; anorexia; drug eruption; multiple cycle treatment; neoplasm recurrence, local; leukopenia; nausea; stomatitis; thrombocytopenia; vomiting; deep vein thrombosis; dose-response relationship, drug; abdominal pain; aminotransferase blood level; chill; dizziness; drug dose escalation; pruritus; lung embolism; drug fatality; drug induced headache; hypokalemia; hyponatremia; rigor; oxcarbazepine; phenobarbital; meningeal neoplasms; blood sampling; glioblastoma; xerostomia; oligodendroglioma; maximum plasma concentration; time to maximum plasma concentration; drug metabolism; meningioma; drug blood level; leukocyte count; maximum tolerated dose; phase 1 clinical trial; anticonvulsive agent; dry skin; quinazolines; phenytoin; hypertriglyceridemia; anticonvulsants; urticaria; granulocytopenia; pharmacokinetics; desquamation; carbamazepine; osi 420; cp 396059; primidone
Journal Title: Neuro-Oncology
Volume: 12
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2010-01-01
Start Page: 87
End Page: 94
Language: English
DOI: 10.1093/neuonc/nop017
PUBMED: 20150371
PROVIDER: scopus
PMCID: PMC2940559
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: NEURJ" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Andrew Lassman
    111 Lassman
  2. Lauren E Abrey
    276 Abrey