Abstract
Diarrhea occurs in approximately half of patients with metastatic renal cell carcinoma (mRCC) receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI). We evaluated the relationship between VEGF-TKI-related diarrhea and stool microbiota. Stool samples were collected from 20 mRCC patients receiving VEGF-TKIs. 16S rRNA sequencing was used to characterize the stool bacteriomic profiling of patients. Assay validation with Salmonella typhimurium spike-in experiments suggested greatest speciation with use of the V5 region. Higher levels of Bacteroides spp. and lower levels of Prevotella spp. were found in patients with diarrhea. In addition, patients receiving VEGF-TKIs with mRCC appeared to have less relative abundance of Bifidobacterium spp. as compared with previous reports based on healthy subjects. We have thus demonstrated interplay between microbiota and VEGF-TKI-induced diarrhea. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in VEGF-TKI-related diarrhea.
Highlights
The systemic therapy of metastatic renal cell carcinoma has evolved markedly over the past decade with the advent of targeted treatments
Patients receiving VEGF-TKIs with metastatic renal cell carcinoma (mRCC) appeared to have less relative abundance of Bifidobacterium spp. as compared with previous reports based on healthy subjects
The first category is composed of five agents—one monoclonal antibody and four small-molecule VEGF-tyrosine kinase inhibitors (VEGF-TKI; sunitinib, sorafenib, pazopanib, and axitinib)
Summary
The systemic therapy of metastatic renal cell carcinoma (mRCC) has evolved markedly over the past decade with the advent of targeted treatments. Approved treatments for this disease fall into two mechanistic categories: (i) inhibitors of VEGF and its cognate receptor, and (ii) inhibitors of the mTOR [1]. The first category is composed of five agents—one monoclonal antibody (bevacizumab) and four small-molecule VEGF-tyrosine kinase inhibitors (VEGF-TKI; sunitinib, sorafenib, pazopanib, and axitinib). Two mTOR inhibitors are currently approved, everolimus and temsirolimus. In the first-line setting, patterns of care data suggest that the preponderance of patients receive VEGF-TKIs [2]. VEGF-TKIs carry indications for use after failure of first-line therapy
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