The characterization, management, and future considerations for ErbB-family TKI-associated diarrhea.

Abstract

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.

• Authors: Hope S Rugo, Jack A Di Palma, Debu Tripathy, Richard Bryce, Susan Moran, Elizabeth Olek, Linda Bosserman
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 175 Issue 1 Pg. 5-15 (May 2019) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 30671765 (Publication Type: Journal Article, Meta-Analysis, Review)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• ErbB Receptors

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Breast Neoplasms (complications, drug therapy)
• Diagnosis, Differential
• Diarrhea (diagnosis, epidemiology, etiology, therapy)
• Disease Management
• ErbB Receptors (antagonists & inhibitors)
• Female
• Humans
• Incidence
• Lung Neoplasms (complications, drug therapy)
• Male
• Post-Exposure Prophylaxis
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Severity of Illness Index
• Time Factors