The relationship between lapatinib concentrations in tumor and plasma from clinical samples.

<p>Women with early stage HER2+ breast cancer were randomized to oral lapatinib monotherapy at 500 mg twice daily (BID), 1000 mg once daily (QD), or 1500 mg QD. Lapatinib concentrations (μM) in plasma (C_P) and tumor (C_T) tissue samples obtained simultaneously 9–15 days after initiating therapy (steady state) concentrations (C_min). (<b>A</b>). Lapatinib concentrations for each patient in the indicated treatment groups. The dotted blue line represents the reported IC₉₀ value for lapatinib in HER2+ breast cancer cell lines. Large circles represent group medians. (<b>B</b>) The complex relationship between lapatinib concentration in tumor and plasma showing a speculative model that suggests determinants: target protein binding (lower Emax curve), and net uptake/efflux (upper Emax curve): grey circle (patient with dysfunctional ABCB1 SNP C3435T); open circle (patient taking lapatinib 500 mg BID also taking grape seed oil), shown with simulation and deviations (dashed lines) illustrating speculation of diminished efflux (left shift) and increased EGFR target binding (right shift). The horizontal dotted line at 4 μM represents the IC₅₀ for the ABCB1 transporter.