Tumor growth velocity: A modified tumor growth rate defining tumor progression during sorafenib treatment in patients with metastatic renal cell carcinoma

Objectives To investigate the role of tumor growth velocity in defining tumor progression in metastatic renal cell carcinoma patients treated with the vascular endothelial growth factor tyrosine kinase inhibitor, sorafenib. Methods A modified calculation for tumor growth velocity was introduced to evaluate the tumor growth velocity, before and after sorafenib withdrawal. Known prognostic factors together with tumor growth velocity before drug withdrawal and tumor growth velocity after drug withdrawal were compared using a chi(2)-test from a contingency table, and partial likelihood test from a Cox regression model for overall survival. Results A total of 114 patients who reached progressive disease and withdrew from sorafenib were enrolled after a median follow-up period of 107.8 months. Tumor growth velocity before drug withdrawal was 7.347 +/- 4.040, and tumor growth velocity after drug withdrawal was 11.647 +/- 5.937 (P < 0.001). Higher tumor growth velocity before drug withdrawal was correlated with a higher risk Memorial Sloan Kettering Cancer Center score (P = 0.022), Karnofsky Performance Status <80 (P = 0.028), non-clear cell carcinoma (P = 0.037), higher tumor nucleus grade (P < 0.001) and best treatment response (P < 0.001). Patients with tumor growth velocity before drug withdrawal >5.0 had shorter overall survival (P < 0.001). On multivariate analysis, factors associated with overall survival were high/intermediate Memorial Sloan Kettering Cancer Center risk score (hazard ratio 2.119, P = 0.006), non-clear histological subtype (hazard ratio 1.900, P = 0.031), tumor growth velocity before drug withdrawal >= 5.0 (hazard ratio 2.758, P < 0.001) and progressive disease as best response (hazard ratio 2.069, P = 0.001). Conclusions Significantly faster tumor growth can be observed if sorafenib is discontinued in the case of disease progression. Thus, we suggest not to withdraw targeted agents until tumor growth velocity is >5.0.