No abstract

As newer, molecularly targeted, anticancer drugs are entering clinical practice, a wide array of previously unrecognised and ill defined side effects of these drugs are increasingly observed. Sorafenib and sunitinib are two of these novel agents, acting on tumour angiogenesis as well as on other key proliferative pathways; recently approved for the treatment of advanced kidney cancer, they may cause peculiar cutaneous, vascular and mucosal toxicities, including hand-foot skin reaction, skin rash, hypertension and GERD-like oesophagitis/gastritis. In this review, we shall deal with these poorly recognised, but sometimes extremely distressing, toxicities; pathophysiologic mechanisms will be discussed and suggestions for treatment of each toxicity will be proposed, based on the few pieces of evidence available and, especially, on our empirical experience.

To identify factors that might predict response to sunitinib in patients with renal cell carcinoma, we measured serum vascular endothelial growth factor (VEGF) and neutrophil gelatinase-associated lipocalin (NGAL) levels. A total of 85 patients were selected and, using the Motzer classification, 46 were assigned to the good- and 38 to the intermediate-risk groups. With univariate Cox analysis, both baseline serum VEGF and NGAL titers, determined by enzyme-linked immunosorbent assay, significantly predicted progression-free survival. For each biomarker, a threshold value was identified, which proved useful to classify patients into groups having titers above or below the thresholds. We then stratified patients according to the two dichotomous variables into good-, intermediate-, and poor-risk groups, and found significantly different progression-free survival rates ranging from 3.5 to 11.6 months. Both VEGF and NGAL maintained their predictive significance at bivariate analysis. Our study shows that serum levels of VEGF and NGAL are significant predictors of progression-free survival in patients with renal cell carcinoma treated with sunitinib.