Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer

• Yokota, Hayato

• Sato, Kazuhiro

• Sakamoto, Sho

• Okuda, Yuji

• Asano, Mariko

• Takeda, Masahide

• Nakayama, Katsutoshi

• Miura, Masatomo

Abstract

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.

Journal

• Biology

  Biology 10 (1054), 1054-, 2021

  MDPI

Keywords

• afatinib
• diarrhea
• limited sampling strategy
• plasma concentration
• therapeutic drug monitoring

Details

• CRID: 1050008754651051520
• NII Article ID: 120007172095
• ISSN: 20797737
• DOI: 10.3390/biology10101054
• HANDLE: 10295/00005837
• Web Site: https://air.repo.nii.ac.jp/records/5520
• Web Site: https://www.mdpi.com/2079-7737/10/10/1054/pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN