High-Trough Plasma Concentration of Afatinib Is Associated with Dose Reduction

Cancers

卷:13

Takayuki Takahashi¹  Hideki Sugawara¹  Yasuo Takeda¹  Hideyuki Terazono¹  Mina Nitta¹  Junko Arima¹  Ryuji Ikeda²  Takayuki Suetsugu³  Hiromasa Inoue³  Keiko Mizuno³  Toru Tanabe⁴  Kayu Okutsu⁵ 

[1] Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan;

[2] Department of Pharmacy, University of Miyazaki Hospital, Miyazaki 889-1692, Japan;

[3] Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan;

[4] Sendai Medical Association Hospital, Sendai 895-0005, Japan;

[5] United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan;

关键词: afatinib;    epidermal growth factor receptor;    tyrosine kinase inhibitor;    non-small-cell lung cancer;    trough plasma concentration;    receiver operating characteristic curve;   

DOI  :  10.3390/cancers13143425

来源: DOAJ

【 摘 要 】

Afatinib is used to treat non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation as a second-generation EGFR-tyrosine kinase inhibitor (TKI). Early prediction of adverse effects based on the pharmacokinetics of afatinib enables support for quality of life (QOL) in patients with no change in efficacy. We examined the pharmacokinetic relationship between trough plasma concentration and adverse effects and evaluated the utility of measuring the trough plasma concentration of afatinib as the first EGFR-TKI treatment for NSCLC in a prospective multicenter study. Twenty-four patients treated with afatinib were enrolled in this study. All blood samples were collected at the trough point, and plasma concentrations were measured using high-performance liquid chromatography–tandem mass spectrometry. Logistic regression analysis for the dose reduction of afatinib was performed, and the receiver operating characteristic (ROC) curve was plotted. Although all patients started afatinib at 40 mg/day, plasma concentrations were variable, and mean and median trough plasma concentrations were 32.9 ng/mL and 32.5 ng/mL in this study, respectively. Minimum and maximum trough plasma concentrations were 10.4 ng/mL and 72.7 ng/mL, respectively. This variability was speculated to involve personal parameters such as laboratory data. However, no patient characteristics or laboratory data examined correlated with the trough plasma concentration of afatinib, except albumin. Albumin showed a weak correlation with plasma concentration (r = 0.60, p = 0.009). The trough plasma concentration of afatinib was significantly associated with the dose reduction of afatinib (p = 0.047). The area under the ROC curve (AUC) for the trough plasma concentration of afatinib was 0.81. The cut-off value was 21.4 ng/mL. The sensitivity and specificity of the cut-off as a risk factor were 0.80 and 0.75. In summary, the trough plasma concentration of afatinib was associated with continued or reduced dosage because of the onset of several adverse effects, and a threshold was seen. Adverse effects not only lower QOL but also hinder continued treatment. Measuring plasma concentrations of afatinib appears valuable to predict adverse effects and continue effective therapy.

【 授权许可】

Unknown