Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer
2021
Yokota, Hayato | Sato, Kazuhiro | Sakamoto, Sho | Okuda, Yuji | Asano, Mariko | Takeda, Masahide | Nakayama, Katsutoshi | Miura, Masatomo
We evaluated the area under the plasma concentration–time curve (AUC) of afatinib required to avoid the onset of grade 2 or higher diarrhea. The C₀ and AUC₀–₂₄ of afatinib were significant higher in patients with grade 2 diarrhea than in those with grade 0–1 diarrhea. The areas under the receiver operator curves were 0.795 with the highest sensitivity (89%) and specificity (74%) at an AUC₀–₂₄ threshold of 823.5 ng·h/mL, and 0.754 with the highest sensitivity (89%) and specificity (74%) at a C₀ threshold of 28.5 ng/mL. In Kaplan–Meier analysis based on these cut-off AUC₀–₂₄ and C₀ values, the median time to the incidence of grade 2 diarrhea was 16 days. The predicted AUC₀–₂₄ of afatinib from the single point of C₆ showed the highest correlation with the measured AUC₀–₂₄ (r² = 0.840); however, a significant correlation between the AUC₀–₂₄ and C₀ was also observed (r² = 0.761). C₀ could be used as a marker of therapeutic drug monitoring because afatinib C₀ was related to AUC₀–₂₄. Therefore, afatinib C₀ should be monitored on day 8 after beginning therapy, and the daily dose of afatinib should be adjusted as an index with a cut-off value of 28.5 ng/mL.
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