Abstract
Treatment for non-small-cell lung cancer (nsclc) is moving away from traditional chemotherapy toward personalized medicine. The reversible tyrosine kinase inhibitors (tkis) erlotinib and gefitinib were developed to target the epidermal growth factor receptor (egfr). Afatinib, an irreversible ErbB family blocker, was developed to block egfr (ErbB1), human epidermal growth factor receptor 2 (ErbB2), and ErbB4 signalling, and transphosphorylation of ErbB3. All of the foregoing agents are efficacious in treating nsclc, and their adverse event profile is different from that of chemotherapy. Two of the most common adverse events with egfr tkis are rash and diarrhea. Here, we focus on diarrhea. The key to successful management of diarrhea is to treat early and aggressively using patient education, diet, and antidiarrheal medications such as loperamide. We also present strategies for the effective assessment and management of egfr tki-induced diarrhea.
Highlights
Non-small-cell lung cancer, with its three main histologic subtypes, adenocarcinoma, squamous cell carcinoma, and large cell anaplastic carcinoma, accounts for approximately 85% of all lung cancers[1,2]
Diarrhea induced by egfr tkis is most likely to occur in the first 4 weeks after treatment initiation[19,20]; diarrhea induced by afatinib is most likely to occur within the first 7 days[21]
Laboratory tests can rule out some causes of diarrhea: neutropenia can be detected from a complete blood count and differential, renal function and electrolyte abnormalities can be assessed using blood tests, and bacterial pathogens can be checked through a stool culture or Clostridium difficile toxin screen
Summary
Non-small-cell lung cancer (nsclc), with its three main histologic subtypes, adenocarcinoma, squamous cell carcinoma, and large cell anaplastic carcinoma, accounts for approximately 85% of all lung cancers[1,2]. In nsclc patients with either an EGFR mutation (10%–15% of white[4] and 20%–40% of Asian[5] nsclc patients) or an ALK mutation (3%–5% of nsclc patients)[6,7], the approach to treatment is moving toward targeted agents Many such patients will receive chemotherapy, targeted agents allow for a personalized approach to treatment through identification of the presence of gene profiles or disease-specific genes that control cancer growth. The irreversible egfr tkis, such as afatinib and dacomitinib, were developed to overcome resistance to the reversible egfr tkis by binding irreversibly to the active site of the kinase domain of egfr[16] They simultaneously inhibit multiple ErbB receptors and oncogenic pathways. Adverse events (aes) with the egfr tkis are different from those with chemotherapy, the most frequent and manageable being rash and diarrhea[8]
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