A pilot, pharmacokinetic (PK), and pharmacodynamic (PD) study to determine the feasibility of intrapatient dose escalation to tolerable rash and the activity of maximal doses of erlotinib (E) in previously treated patients with advanced non-small cell lung cancer (NSCLC)

3045 Background: The recommended dose of the epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor E may have been based in part on skin rash grade, which may not reflect maximal tolerability. Moreover, since clinical benefit with E and other EGFR inhibitors appears to correlate with the dose-dependent rash, this trial sought to determine the feasibility of intrapatient dose escalation to achieve a maximally tolerated “target” rash and to determine the antitumor efficacy of E at its true maximally tolerated dose in patients with advanced NSCLC. PK and PD studies of signal transduction elements related to EGFR were performed in skin, hair follicles, serum, and tumor. Methods: The starting E dose, 150 mg/day, was increased step-wise in each patient to 200 mg and then in 25 mg increments every 14 days unless an intolerable rash occurred (as defined by: requirement for narcotics or systemic corticosteroids; desquamation of >25% of body-surface area; generalized urticaria; or if the rash was consi...