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- Title
Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer.
- Authors
Yokota, Hayato; Sato, Kazuhiro; Sakamoto, Sho; Okuda, Yuji; Asano, Mariko; Takeda, Masahide; Nakayama, Katsutoshi; Miura, Masatomo
- Abstract
Simple Summary: Higher afatinib plasma concentrations have been reported to be associated with the severity of diarrhea; however, the specific target plasma concentration of afatinib required to avoid severe diarrhea onset is unclear. We found that an afatinib AUC0–24 of greater than or equal to 823.5 ng·h/mL and C0 of greater than or equal to 28.5 ng/mL may be used as cut-off values for the incidence of afatinib-induced grade 2 diarrhea. A significant correlation between the AUC0–24 and C0 of afatinib was observed (r2 = 0.761; p < 0.001). Therefore, we could use C0 as a marker of therapeutic drug monitoring. In the current study, the median time to the incidence of grade 2 diarrhea in patients with a C0 of more than 28.5 ng/mL was 16 days. Therefore, we recommend monitoring the C0 of afatinib on day 8 after the beginning of afatinib therapy. 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.
- Subjects
NON-small-cell lung carcinoma; AFATINIB; DRUG monitoring; DIARRHEA; DRUG dosage
- Publication
Biology (2079-7737), 2021, Vol 10, Issue 10, p1054
- ISSN
2079-7737
- Publication type
Article
- DOI
10.3390/biology10101054