2007 ESTIMATED GFR AS A BIOMARKER OF EFFICACY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH SUNITINIB

Abstract

INTRODUCTION AND OBJECTIVES: Renal dysfunction is frequent side effect of VEGFR-inhibitors, especially sunitinib. We investigated the association of renal function change during VEGFR-inhibitors administration and antitumor efficacy in patients with metastatic renal cell carcinoma (mRCC). METHODS: Retrospective data were collected for mRCC patients received VEGF-targeted therapy between January 2005 and October 2011. We investigated renal adverse events and clinically significant increased serum creatinine level in patients who received VEGF targeted therapy. GFR was estimated with the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: Ninety three patients with mRCC who received sunitinib (n 46), sorafenib (n 38), axitnib (n 9) were included in this analysis. During administration, gradual and significant increase of serum creatinine was observed in 34 (73.9 %) sunitinib recipients compared with sorafenib (15.2 %) or axitinib (33.3 %) recipients (p 0.041). Significant decrease of estimated GFR (eGFR) compared to baseline correlated with increase of serum creatinine level developed in ‘on’ period of 6 sunitinib administration cycle (p 0.013). No significant change was observed in serum creatinine level and eGFR in patients received other VEGF-targeted agents. Decrease of eGFR in the first ‘on’ period was associated with less frequent tumor response to sunitinib and a short time to disease progression (p 0.028 and 0.042). CONCLUSIONS: Our data suggest that nephrotoxicity developed in a high percentage of patients on sunitinib compared for sorafenib and axitinib in mRCC patients. In patients with mRCC, sunitinib-associated renal function impairment in the first ‘on’ period may be an efficacy biomarker.