hide
Free keywords:
Animals
Antineoplastic Agents/*administration & dosage
Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology/genetics/pathology
Cell Line, Tumor
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Administration Schedule
ErbB Receptors/antagonists & inhibitors/genetics/metabolism
Erlotinib Hydrochloride/*administration & dosage
Humans
Lung Neoplasms/*drug therapy/enzymology/genetics/pathology
Male
Mice
Mice, Nude
Protein Kinase Inhibitors/*administration & dosage
Xenograft Model Antitumor Assays
Egfr
Nsclc
Pet
erlotinib
high-dose scheduling
Abstract:
Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy.
