Intermittent high dose treatment with erlotinib enhances therapeutic efficacy in EGFR mutant lung cancer
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.
Oncotarget