| Summary: | 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 C<sub>0</sub> and AUC<sub>0–24</sub> 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 AUC<sub>0–24</sub> threshold of 823.5 ng·h/mL, and 0.754 with the highest sensitivity (89%) and specificity (74%) at a C<sub>0</sub> threshold of 28.5 ng/mL. In Kaplan–Meier analysis based on these cut-off AUC<sub>0–24</sub> and C<sub>0</sub> values, the median time to the incidence of grade 2 diarrhea was 16 days. The predicted AUC<sub>0–24</sub> of afatinib from the single point of C<sub>6</sub> showed the highest correlation with the measured AUC<sub>0–24</sub> (<i>r<sup>2</sup></i> = 0.840); however, a significant correlation between the AUC<sub>0–24</sub> and C<sub>0</sub> was also observed (<i>r<sup>2</sup></i> = 0.761). C<sub>0</sub> could be used as a marker of therapeutic drug monitoring because afatinib C<sub>0</sub> was related to AUC<sub>0–24</sub>. Therefore, afatinib C<sub>0</sub> 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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