Side effects of tyrosine kinase inhibitors therapy in patients with non‑small cell lung cancer and associations with EGFR polymorphisms: A systematic review and meta‑analysis

Abstract

Rash and diarrhea are common side effects of tyrosine kinase inhibitor (TKI) therapy administered to patients with non-small cell lung cancer (NSCLC). The polymorphisms of the epidermal growth factor receptor (EGFR) gene may be a potential predictor of these side effects. The aim of the present meta-analysis was to examine the association of EGFR polymorphisms and TKI-associated toxicities. Electronic databases (PubMed, Scopus and ISI Web of Science) were searched for relevant studies. According to the inclusion and exclusion criteria, a search of the databases identified 4,918 results, among which 6 clinical trials were obtained with 1,318 patients with NSCLC. A total of 9 EGFR single nucleotide polymorphisms (SNPs) associated with TKI toxicity were identified including, rs11568315, rs712829, rs712830, rs2227983, rs2075102, rs2293347, rs11977388, rs4947492 and rs884225. The data associated with skin toxicity from rs11568315, rs712829 and rs712830 were analyzed in the present meta-analysis. Data from rs11568315 were also analyzed in relation to diarrhea. Among all the examined SNPs, statistically significant results were obtained under the dominant genetic model for CA repeats in rs11568315 (SS vs. SL+LL) with skin toxicity. The long CA repeat (SL+LL) carriers were more likely to experience skin toxicity associated with TKIs (P=0.005). By contrast, there was no significant result for diarrhea (P=0.661) under dominant genetic model for CA repeats.

Influence of Smoking Habits on the Efficacy of EGFR-TKI Therapy in Patients with Advanced NSCLC: A Systematic Review and Meta-Analysis

“…The most common serious adverse events in both Asians and Caucasians after EGFR-TKIs treatment were rash and diarrhea, which is consistent with the previous reports. 31 Impaired liver function with increased aspartate aminotransferase (AST) and alanine transaminase (ALT) was also found particular in Asians, whereas anorexia was only found in Caucasians, suggested that adverse events of TKIs were different between the 2 populations. The EGFR variants in different populations may explain the difference.…”

“…The EGFR variants in different populations may explain the difference. 31 This study aimed to explore the efficacy of EGFR-TKIs in patients with different smoking habits and provide evidences of effective treatments for NSCLC patients who smoke. However, this study inevitably still has some limitations: (1) Even though the distribution of EGFR is different in Caucasians compared with Asians, studies focus on both Caucasians and Asians were still included.…”

Management of diarrhea induced by EGFR-TKIs in advanced lung adenocarcinoma

“…Data associated with diarrhea from rs11568315 were analyzed, but the difference was not significant (p = 0.661). 41 Bacterial overgrowth can also be a risk factor for diarrhea. It can be promoted by previous radiotherapy, colectomy, or altered gut motility derived from concomitant therapies 42 and medications (prokinetic agents, laxatives, proton pump inhibitors, trimebutine, and acid reducers or comorbidities such as irritable bowel syndrome, inflammatory bowel disease, and gastrointestinal surgery).…”

Evaluation of the therapeutic effects and tolerability of modified lenvatinib administration methods for unresectable hepatocellular carcinoma: A preliminary study

“…LEN is a standard therapeutic agent for hepatocellular carcinoma, but the high incidence of adverse events (AEs) is a problematic aspect of LEN treatment (1)(2)(3)(4), since these AEs may necessitate treatment discontinuation. Rash and diarrhea are common side effects of tyrosine kinase inhibitor (TKI) therapy administered to patients with non-small cell lung cancer (5). The most common any-grade AEs of LEN are hypertension (42%), diarrhoea (39%), decreased appetite (34%), decreased weight (31%), and fatigue (30%) (2).…”