TY - JOUR
T1 - The characterization, management, and future considerations for ErbB-family TKI-associated diarrhea
AU - Rugo, Hope S.
AU - Di Palma, Jack A.
AU - Tripathy, Debu
AU - Bryce, Richard
AU - Moran, Susan
AU - Olek, Elizabeth
AU - Bosserman, Linda
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/5/15
Y1 - 2019/5/15
N2 - Purpose: Diarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea. Methods: This paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management. Results: In the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed—and continue to be refined—to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea. Conclusions: Continued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity.
AB - Purpose: Diarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea. Methods: This paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management. Results: In the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed—and continue to be refined—to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea. Conclusions: Continued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity.
KW - Cancer
KW - Diarrhea
KW - ErbB receptor
KW - Tyrosine kinase inhibitor
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U2 - 10.1007/s10549-018-05102-x
DO - 10.1007/s10549-018-05102-x
M3 - Review article
C2 - 30671765
AN - SCOPUS:85060535884
SN - 0167-6806
VL - 175
SP - 5
EP - 15
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -