Background: Almost 30% of the sunitinib-treated patients for metastatic renal carcinoma (mRCC) do not
receive a clinical benefit. Convincing evidences demonstrated a cross talk between the VEGF and CXCR4 pathways. It
was hypothesized that CXCR4 expression in primary renal cancer could predict sunitinib responsiveness.
Patients and Methods: In this exploratory study sixty-two mRCC patients receiving sunitinib as first-line treatment were
evaluated for CXCR4 expression through immunohistochemistry (IHC). Correlations between CXCR4 expression,
baseline patients and tumour characteristics were studied by contingency tables and the chi-square test. Univariable
analysis was performed with the log-rank test, and the Cox model was applied for multivariable analysis.
Results: The objective response rate of sunitinib first-line therapy was 35.5% (22/62) with a disease control rate (response
and stable disease) of 62.9% (39/62). CXCR4 expression was absent/low in 30 (48.4%), moderate in 17 (27.4%), and high
in 15 (24.2%) tumors respectively. Low or absent CXCR4 expression predicted response to sunitinib therapy. Moreover,
Fuhrman grading and concomitant, CXCR4 and Fuhrman grading, strongly predicted sunitinib first line therapy
responsiveness on progression-free survival and overall survival.
Conclusions: High CXCR4 expression correlates with sunitinib poor response in metastatic renal cancer
Keywords: CXCR4, first-line therapy, mRCC, response to therapy, sunitinib, survival analyses, Response Evaluation Criteria in Solid Tumors (RECIST), ANOVA, GAPDH expression, CXCR4-Fuhrman grading concomitant
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