Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

Abstract

Patients with advanced stage non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations using EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib and afatinib as first-line treatment had better progression-free survival, overall response rate and quality of life than those on chemotherapy. Although EGFR TKIs are commonly associated with skin-related (rash, xerosis and paronychia) and gastrointestinal-related (diarrhea and stomatitis) adverse events (AEs), these effects are usually mild. But severe cases can occur, significantly affecting patient's well-being, treatment compliance and quality of life. Therefore, patient education, early diagnosis, and prophylactic treatment are important strategies to optimally manage EGFR TKI-related adverse effects. In this review, we summarize the commonly encountered EGFR TKI-related AEs and provide a current overview of AE management in local practice with a focus on Asian patients. K E Y W O R D Sadverse drug events, gastrointestinal tract, mutations, non-small cell lung cancer, skin BACKGROUNDEighty percent of lung cancers are advanced-stage non-small cell lung cancer (NSCLC). (1) Epidermal growth factor receptor (EGFR) gene mutation, which is a major and potent oncogenic driver in NSCLC is a therapeutic target, with EGFR tyrosine kinase inhibitors (EGFR TKIs), altering the pattern of care in patients with advanced stage NSCLC.With EGFR TKIs (erlotinib, gefitinib and afatinib) as first-line treatment for patients with advanced stage NSCLC with sensitizing EGFR mutations, higher progression-free survival, overall response rate and quality of life than chemotherapy can be achieved. 1 These drugs are generally well tolerated as they have a predictable toxicity profile and less serious toxicities than traditional cytotoxic chemotherapy. 2 Nevertheless, EGFR TKIs can still produce severe adverse events (AEs) and impair quality of life.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. wileyonlinelibrary.com/journal/ajco 23

Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea

“…Diarrhea is even more of a problem with second-generation inhibitors, such as afatinib, with greater than 90% of patients affected and a greater incidence of severe diarrhea (9,12). Current management of ErbB TKI-associated diarrhea includes fluid replacement, antimotility agents such as loperamide, and in severe cases, TKI dose reduction or discontinuation (13). Given the morbidity and reduced clinical effectiveness associated with severe diarrhea following ErbB TKI therapy, there remains an unmet need for efficacious, targeted, and safe antidiarrheal therapies.…”

An Unusual Case of Paronychia

“…EGFR TKIs such as erlotinib, gefitinib, afatinib and osimertinib are considered first-line treatment for advanced stage non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutation. As EGFR is mainly expressed in epithelial cells, such as the skin and gastrointestinal tract, the most common adverse effects are cutaneous and gastrointestinal manifestations [1]. Common side effects of EGFR TKI are acneiform rash, mucositis and paronychia.…”

“…Treatment includes local care to all grades which consist of petroleum jelly, cushioning of affected areas, nail trimming, avoidance of irritants substances, avoidance from trauma, aggressive manicure and pedicure and avoidance of prolonged water exposure. Soaking fingers or toes in a solution of diluted antiseptic soaks such as chlorhexidine and white vinegar for 15 minutes every day may be useful 1 . Topical application include potent topical steroid such as betamethasone valerate 0.1% ointment and Clobetasol Proprionate 0.05% in grade 2 and 3 can also be added.…”

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

“…The assessment of AEs should comprehend severity scales like the common terminology criteria for AEs since this may help to assist in treatment reductions/withdrawals [39]. Table 2 describes the most common AEs and strategies to manage them [11,[40][41][42][43][44][45].…”