Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer

Abstract

Non-small-cell lung cancer (nsclc) has the highest prevalence of all types of lung cancer, which is the second most common cancer and the leading cause of cancer-related mortality in Canada. The need for more effective and less toxic treatment options for nsclc has led to the development of agents targeting the epidermal growth factor receptor (egfr)-mediated signalling pathway, such as egfr tyrosine kinase inhibitors (egfr-tkis). Although egfr-tkis are less toxic than traditional anti-neoplastic agents, they are commonly associated with acneiform-like rash and diarrhea. This review summarizes the clinical presentation and causes of egfr-tki-induced rash and diarrhea, and presents strategies for effective assessment, monitoring, and treatment of these adverse effects. Strategies to improve the management of egfr-tki-related adverse events should improve clinical outcomes, compliance, and quality of life in patients with advanced nsclc.

Keywords: Epidermal growth factor receptor; adverse drug event; adverse drug reaction; diarrhea; skin rash.

Figures

FIGURE 1

Rash induced by epidermal growth factor receptor.

FIGURE 2

Management of rash induced by epidermal growth factor receptor (egfr) tyrosine kinase inhibitor (tki). ctcae = Common Terminology Criteria for Adverse Events; adl = activities of daily living. Adapted from Eaby et al., 2008 ; Harandi et al., 2009 ; Lynch et al., 2007 . a Guidelines presented here recommend treatment with minocycline for moderate-to-severe rash only. However, early treatment of mild rash can prevent the development of more severe forms and the need for higher, more toxic doses of minocycline. Early treatment of mild rash with 50 mg minocycline plus 1% hydrocortisone is therefore a reasonable option. b Topical steroids should be pulsed according to institution guidelines.

FIGURE 3

Management of diarrhea induced by epidermal growth factor receptor (egfr) tyrosine kinase inhibitor (tki). Adapted from BC Cancer Agency, 2004 ; Moore et al., 2007 ; and Saltz, 2003 . a Starting dose is 4 mg, followed by 2 mg for a maximum of 20 mg daily.