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

Autor: Michael D, Prados, Kathleen R, Lamborn, Susan, Chang, Eric, Burton, Nicholas, Butowski, Mary, Malec, Ami, Kapadia, Jane, Rabbitt, Margaretta S, Page, Ann, Fedoroff, Dong, Xie, Sean K, Kelley
Rok vydání: 2006
Předmět:
Zdroj: Neuro-oncology. 8(1)
ISSN: 1522-8517
Popis: The purpose of this study was to define the maximum tolerated dose of erlotinib and characterize its pharmacokinetics 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. Eighty-three 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.
Databáze: OpenAIRE