Phase 1 study of erlotinib HCl alone and combined with temozolomide in patients with stable or recurrent malignant glioma.

Abstract:

:The purpose of this study was to define the maximum tolerated dose of erlotinib and characterize its pharmaco-kinetics and safety profile, alone and with temozolomide, with and without enzyme-inducing antiepileptic drugs (EIAEDs), in patients with malignant gliomas. Patients with stable or progressive malignant primary glioma received erlotinib alone or combined with temozolomide in this dose-escalation study. In each treatment group, patients were stratified by coadministration of EIAEDs. Erlotinib was started at 100 mg orally once daily as a 28-day treatment cycle, with dose escalation by 50 mg/day up to 500 mg/day. Temozolomide was administered at 150 mg/m2 for five consecutive days every 28 days, with dose escalation up to 200 mg/m2 at the second cycle. Eightythree patients were evaluated. Rash, fatigue, and diarrhea were the most common adverse events and were generally mild to moderate. The recommended phase 2 dose of erlotinib is 200 mg/day for patients with glioblastoma multiforme who are not receiving an EIAED, 450 mg/day for those receiving temozolomide plus erlotinib with an EIAED, and at least 500 mg/day for those receiving erlotinib alone with an EIAED. Of the 57 patients evaluable for response, eight had a partial response (PR). Six of the 57 patients had a progression-free survival of longer than six months, including four patients with a PR. Coadministration of EIAEDs reduced exposure to erlotinib as compared with administration of erlotinib alone (33%-71% reduction). There was a modest pharmacokinetic interaction between erlotinib and temozolomide. The favorable tolerability profile and evidence of antitumor activity indicate that further investigation of erlotinib is warranted.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Prados MD,Lamborn KR,Chang S,Burton E,Butowski N,Malec M,Kapadia A,Rabbitt J,Page MS,Fedoroff A,Xie D,Kelley SK

doi

10.1215/S1522851705000451

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

67-78

issue

1

eissn

1522-8517

issn

1523-5866

pii

8/1/67

journal_volume

8

pub_type

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