EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction

摘要: // Nesaretnam Barr Kumarakulasinghe 1, * , Nicholas Syn 2, 3, Yu Yang Soon 4 Atasha Asmat 5 Huili Zheng 6 En Yun Loy Brendan Pang 7 Ross Andrew Soo 2 1 Department of Haematology-Oncology, National University Cancer Institute, Singapore Science Institute Singapore, 3 Yong Loo Lin School Medicine, Radiation Oncology, General Surgery, Tan Tock Seng Hospital, Registry Diseases Office, Health Promotion Board, Pathology, System, These authors have contributed equally to this work as co-first Correspondence to: Soo, email: ross_soo@nuhs.edu.sg Keywords: gefitinib, erlotinib, drug-drug interactions, NSCLC, gastric acid suppression Received: August 19, 2016      Accepted: October 27, Published: November 2016 ABSTRACT Background: Erlotinib and gefitinib are weak base drugs whose absorption clinical efficacy may be impaired by concomitant suppressive (AS) therapy, yet proton pump inhibitors (PPIs) histamine-2 receptor antagonists (H2As) widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention treatment erlotinib-induced gastrointestinal injury corticosteroid-associated irritation. We assessed relevance potential interaction (DDI) a retrospective cohort EGFR -mutant NSCLC patients. Results: The AS usage rate was 35%. In overall cohort, users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 – 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR 1.37, 0.89 2.12, 0.16; 7.6 8.7 compared with non-users multivariate Cox regression analysis. However, subgroup analyses that associated significantly who had fewer milder comorbidities (Charlson comorbidity index ≤ 2), those Karnofsky performance status < 90, never-smokers. Materials Methods: A database analysis 157 given erlotinib advanced from two institutions conducted. Patients were classified AS-users if periods anti-EGFR therapy overlapped ≥ 30%. Overall survival (OS) progression-free (PFS) according usage. Conclusions: Concomitant an adverse impact on and/or cohort. Our findings should regarded exploratory require replication large prospective