Phase I and pharmacokinetic study of bexarotene in combination with gefitinib in the third-line treatment of non-small-cell lung cancer: brief report.

摘要: Gefitinib (an epidermal growth factor receptor tyrosine kinase inhibitor) and bexarotene (a rexinoid) affect similar oncogenic pathways are both metabolized through cytochrome P450 CYP3A4. We studied the combination of gefitinib in third-line treatment advanced non-small-cell lung cancer to examine pharmacokinetic interactions establish maximum tolerated dose. This was a single-institution, nonrandomized, open-label, phase I clinical trial with standard 3+3 dose escalation. Three patients were enrolled at each level on basis analysis 1 including (Iressa) 250 mg oral daily (Targretin) 400 mg/m +1 500 daily. Patients received alone for 2 weeks allow steady state thereafter, added. In 1, two three had undetectable levels day 15 unknown reasons. However, peak 29 all receiving lower than published levels. Among +1, ∼40% plasma concentrations noted compared along mean 44% reduction area under concentration-time curve from 0 24 h (AUC0-24). Bexarotene appears C max AUC0-24 Our results have implications ongoing trials that combine other small molecules era personalized therapy.