title: Diarrhea associated with afatinib: an oral ErbB family blocker.
abstract: Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGF receptor (EGFR; also known as HER1 or ErbB1) tyrosine kinase inhibitor therapy. GI AEs are among the most common and most impactful on a patient's quality of life. Severe diarrhea can result in fluid and electrolyte losses, leading to dehydration, electrolyte imbalances and renal insufficiency. Afatinib is an irreversible, oral, ErbB family blocker, inhibiting EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptor kinases. It also inhibits transphosphorylation of ErbB3. Similar to reversible tyrosine kinase inhibitors of EGFR, GI AEs - in particular, diarrhea - have frequently been observed in afatinib-treated patients. This article summarizes current data on afatinib-associated diarrhea and provides strategies for its management. Patient education, early identification, timely management and ongoing assessment will help to prevent aggravation, afatinib dose reductions or therapy discontinuation, encouraging patient compliance and allowing patients to obtain the maximum therapeutic benefit from this agent.
authors.affiliation: Graduate Institute of Oncology and Cancer Research Center, National Taiwan University Hospital, Taipei, Taiwan. chihyang@ntu.edu.tw
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.forename: Noemi
authors.initials: N
authors.lastname: Reguart
authors.forename: Jana
authors.initials: J
authors.lastname: Barinoff
authors.forename: Jens
authors.initials: J
authors.lastname: Köhler
authors.forename: Martina
authors.initials: M
authors.lastname: Uttenreuther-Fischer
authors.forename: Uz
authors.initials: U
authors.lastname: Stammberger
authors.forename: Dennis
authors.initials: D
authors.lastname: O'Brien
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
mesh_terms: D000284:Administration, Oral; D000077716:Afatinib; D003967:Diarrhea / Q000139:chemically induced* / Q000178:diet therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D066247:Receptor, ErbB-4
chemical_list: D000077716:Afatinib; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human