Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

• Published in: PloS one Vol. 11; no. 2; p. e0149722
• Main Authors: Chen, Yu-Mu, Lai, Chien-Hao, Chang, Huang-Chih, Chao, Tung-Ying, Tseng, Chia-Cheng, Fang, Wen-Feng, Wang, Chin-Chou, Chung, Yu-Hsiu, Wang, Yi-Hsi, Su, Mao-Chang, Liu, Shih-Feng, Huang, Kuo-Tung, Chen, Hung-Chen, Chang, Ya-Chun, Lin, Meng-Chih
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.02.2016; Public Library of Science (PLoS)
• Subjects: Aged; Antacids; Antacids - therapeutic use; Antineoplastic Agents - therapeutic use; Biology and Life Sciences; Biopsy; Brain; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - secondary; Brain research; Cancer; Cancer metastasis; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cerebrospinal fluid; Chemotherapy; Complications and side effects; Critical care; Development and progression; Dosage and administration; Drug interaction; Drug Interactions; Epidermal growth factor; Epidermal growth factor receptors; Female; Hospitals; Humans; Inhibitors; Internal medicine; Liver; Lung cancer; Lung diseases; Male; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Mutation; Nervous system; Non-small cell lung cancer; Non-small cell lung carcinoma; Oncology; Patients; Physicians; Prognosis; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase receptors; Proton pump inhibitors; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Research and Analysis Methods; Retrospective Studies; Risk factors; Survival; Tyrosine; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0149722

Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases. This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users. Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases. Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.