Abstract
Purpose
A variety of tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of solid tumors and hematological cancers. However, TKIs are often associated with gastrointestinal (GI) adverse effects (AEs), especially diarrhea. Therefore, in the present study, we aimed to describe the clinical features and outcomes of TKI-associated lower GI AEs.
Methods
This was a retrospective single-center cohort study of patients with cancer treated with TKIs from March 2016 to September 2020 who experienced diarrhea without other identifiable causes. Basic and GI AE-related characteristics and outcomes were compared using χ2 and Mann–Whitney U tests.
Results
Of 2172 patients who received TKIs over the study period, we included 228 in the final analysis. Of these, 166 (72.8%) had hematological cancers. Besides diarrhea, GI symptoms included nausea (36.4%), vomiting (21.9%), abdominal pain (15.4%), and bleeding (3.1%). Symptoms were typically mild, with 209 patients (91.7%) presenting with Common Terminology Criteria for Adverse Events grade 1–2 diarrhea. Only 5 patients (2.2%) received immunosuppressants for diarrhea treatment, 83 (36.4%) received no treatment, 29 (12.7%) received antibiotics, 101 (44.3%) received supportive antidiarrheal medications, and 17 patients (7.5%) needed TKI dose reduction or cessation of TKI use. When compared with patients with hematological cancers, those with solid tumors had a higher rate of hospitalization (29.0% vs. 7.2%; p < 0.001) and mortality (75.8% vs. 43.4%; p < 0.001) but a lower rate of recurrence of GI AEs (21.0% vs. 42.8%; p = 0.003. Only 15 patients (6.6%) underwent colonoscopy, with normal endoscopic findings in 8 patients (53.3%) and nonulcerative inflammation in 5 patients (33.3%). The inflammation universally involved the left colon. Twelve of the 15 patients who underwent colonoscopy had active colitis. In the hematological cancer group, patients with acute myeloid leukemia had a lower GI AE recurrence rate than did patients with other hematological cancers (7.2% vs. 30.1%; p = 0.001).
Conclusion
Ten percent of cancer patients receiving TKIs experienced lower GI AEs, which were usually mild. Symptoms TKI-related GI adverse effects were nonspecific, often overlapping those of other cancer therapy-related GI AEs. Treatment of GI AEs was largely supportive, with limited roles for antibiotics and immunosuppressants.
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Availability of data and materials
The data sets used and analyzed in this study are available from the corresponding author upon reasonable request.
Abbreviations
- AE:
-
Adverse effect
- CTCAE:
-
Common Terminology Criteria for Adverse Events
- EGFR:
-
Epidermal growth factor receptor
- GI:
-
Gastrointestinal
- ICI:
-
Immune checkpoint inhibitor
- SM-TKI:
-
Small-molecule tyrosine kinase inhibitor
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YW and AT: were the senior authors of the manuscript; they developed the concept, designed the study, interpreted the results, preserved data accuracy and integrity at all stages, were accountable for all aspects of the study, were in charge of the overall direction and planning of the study, and contributed to writing of the manuscript with input from all authors. CL and RA collected the data for the study, conducted and interpreted the data analysis, and wrote the manuscript. MS: contributed to the data analysis. NS, MA, AS, OA, and PO critically revised the final version of the manuscript. All authors read and approved the final manuscript.
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Liu, C., Amin, R., Shatila, M. et al. Clinical characteristics and outcomes of tyrosine kinase inhibitor-related lower GI adverse effects. J Cancer Res Clin Oncol 149, 3965–3976 (2023). https://doi.org/10.1007/s00432-022-04316-3
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DOI: https://doi.org/10.1007/s00432-022-04316-3