APHON Pediatric Chemotherapy-Biotherapy Renewal

Ibrutinib Imatinib (<400 mg/day) Larotrectinib Nilotinib

Pazopanib Ruxolitinib Sorafenib

Temsirolimus Vemurafenib

Venetoclax Vismodegib Referenced with permission from the NCCN Guidelines® for Antiemesis, V.1.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed October 8, 2021. Available online at www.nccn.org.

Diarrhea. Many small molecule inhibitors are associated with diarrhea. Patients taking erlotinib, gefitinib, or other EGFR inhibitors can experience significant diarrhea in up to 25% of cases. The diarrhea associated with vascular endothelial growth factor (VEGF) inhibitors (sorafenib, sunitinib, pazopanib) is usually mild to moderate. But even mild diarrhea can have negative effects on a patient’s well-being when it is caused by a medication that is taken daily for extended periods of time. The etiology of diarrhea caused by small molecule inhibitors may be related to EGF and VEGF receptors in the intestinal epithelium that are inadvertently targeted by the drug, resulting in inhibition of normal gut function. Inflammation, altered chloride secretion, and changes in the intestinal microflora may also play a role. Management generally involves supportive care to avoid dehydration and electrolyte imbalances. After evaluation to exclude other causes of the diarrhea, the use of medications such as loperamide or octreotide to treat prolonged mild or moderate diarrhea may be considered. Further research is needed to better define the pathophysiology of diarrhea caused by small molecule inhibitors, in order to identify specific medications that may prevent symptoms (Secombe et al., 2020). Drug-induced liver injury (chemical hepatitis). Small molecule inhibitors that cause transient elevations in transaminases without hepatotoxicity include erlotinib, gefitinib, imatinib, pazopanib, and nilotinib (and probably others). Hepatic dysfunction caused by imatinib can lead to chronic hepatitis. Severe hepatotoxicity (grade 4 transaminitis) has been reported with crizotinib (Ricart, 2017). Management of hepatocellular injury involves monitoring transaminase and bilirubin levels and withholding the drug if significant elevations occur. Other steps would be to evaluate concurrent medications with hepatic side effects and to evaluation for viral illnesses. Effects on skin and mucous membrane. Skin rashes are very common in patients who are taking small molecule inhibitors that target EGFR.