Using erlotinib to treat patients with non-small cell lung cancer who continue to smoke

Erlotinib is active for unselected patients with advanced non-small cell lung cancer. Patients who smoke, however, are less likely to respond and less likely to experience toxicity. These patients rapidly metabolize erlotinib and experience lower drug exposure when treated with standard doses. A recent dose escalation study established 300 mg daily as the recommended Phase II dose in patients who continue to smoke. Pharmacokinetic profiles of erlotinib in current smokers taking 300 mg daily were comparable to non-smokers taking 150 mg daily. Current smokers taking 300 mg daily had a toxicity profile comparable to the toxicity profile for patients in the BR.21 trial. Determining the best strategy for overcoming erlotinib resistance may require understanding both pharmacokinetic and tumor-specific resistance mechanisms. Individually, the selection and dosing of erlotinib for the treatment of lung cancer patients who continue to smoke is a clinical challenge.