Case series on the association between blood levels and side effects of afatinib maleate.

Purpose: Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug.

Methods: The study subjects were patients who were administered AFA for non-small cell lung cancer. Of these subjects, six patients agreed to participate in the study. The starting dose of AFA was 40 mg/day. We measured trough blood AFA levels on day 1 and 3 after AFA administration, on day 8-12, and every month until AFA administration was discontinued. Side effects were evaluated according to the adverse event codialect standard (CTCAE v.4.0).

Results: A temporary discontinuation and/or reduction in AFA dose (within 2 months) because of diarrhea and stomatitis was needed in four patients. Mean blood AFA levels on day 8-12 in these four patients were significantly higher than in other patients (47.0 ± 9.5 vs. 24.4 ± 0.1 ng/mL, P = 0.017). In addition, mean renal function prior to AFA administration in these four patients was significantly lower than that in the other patients (49.0 ± 9.6 mL/min/1.73 m vs. 77.2 ± 9.0, P = 0.026).

Conclusions: High blood AFA levels were associated with the early discontinuation and/or dose reduction of AFA because of untoward side effects, which may also be associated with decreased renal function.