A review: drug-drug interactions of epithelial growth factor receptor-tyrosine kinase inhibitors.
10.3760/cma.j.cn112152-20210909-00687
- VernacularTitle:表皮生长因子受体酪氨酸激酶抑制剂药物相互作用概述
- Author:
Jia ZHONG
1
;
Jie WANG
1
Author Information
1. Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
- Publication Type:Review
- Keywords:
Acid inhibitory drugs;
Cytochrome P450;
Drug interactions;
Drug transporters;
Epidermal growth factor receptor tyrosine kinase inhibitors;
Lung neoplasms
- MeSH:
ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics*;
Carcinoma, Non-Small-Cell Lung/pathology*;
Drug Interactions;
ErbB Receptors/genetics*;
Humans;
Lung Neoplasms/pathology*;
Mutation;
Neoplasm Proteins/metabolism*;
Protein Kinase Inhibitors/adverse effects*
- From:
Chinese Journal of Oncology
2022;44(7):717-724
- CountryChina
- Language:Chinese
-
Abstract:
Mutations in the epithelial growth factor receptor (EGFR) is a driving factor that causes non-small cell lung carcinoma (NSCLC). The epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a crucial discovery in the treatment of lung cancer, particularly the efficacy of EGFR-TKIs is superior to that of the standard chemotherapy for patients with EGFR mutation-positive advanced NSCLC. Patients with NSCLC use EGFR-TKIs and other medications simultaneously is commonly seen, especially among those with comorbidities, which increases the risk of drug-drug interactions (DDIs) of EGFR-TKIs. The most common mechanisms underlying the DDIs of EGFR-TKIs are modulations of cytochrome P450 (CYP) and drug transporters [including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)], as well as gastrointestinal acid-inhibitory drugs [proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RA)]. Inhibitors or inducers of CYP enzymes and drug transporters can inhibit or accelerate the metabolism of EGFR-TKIs, which increase or reduce the exposure of EGFR-TKIs, thereby affect the efficacy and safety of EGFR-TKIs. In addition, PPIs or H(2)RA can decrease the solubility, bioavailability and efficacy of EGFR-TKIs. This review summarizes the mechanisms of DDIs of gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib; the management recommendations for DDIs of those EGFR-TKIs from the Chinese and global guideline, as well as from the recent pre-clinical and clinical studies, which provide the reference and evidence for managing the combination therapies of EGFR-TKIs and other medications in clinics.
