Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers.

ABSTRACT:

Purpose

Cigarette smoking induces CYP1A1/1A2 and is hypothesized to alter erlotinib pharmacokinetics. This study aimed to determine the maximum tolerated dose (MTD) of erlotinib in advanced non-small-cell lung cancer (NSCLC) patients who smoke and compare the pharmacokinetics of erlotinib at the MTD in current smokers with 150 mg.

Patients and methods

Cohorts of NSCLC patients currently smoking > or = 10 cigarettes per day for > or = 1 year received escalating doses of erlotinib for 14 days until dose-limiting toxicity (DLT). A separate cohort of patients was then randomly assigned to erlotinib at either MTD or 150 mg daily with pharmacokinetics assessed at day 14. Erlotinib was continued until progression or intolerable toxicity.

Results

Four dose levels were evaluat

SUBMITTER: Hughes AN 

PROVIDER: S-EPMC2667823 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature