Pazopanib. Kidney cancer: many risks, but is there a benefit for patients?

Chemotherapy has little impact on renal carcinoma. Interferon alfa is the standard treatment, in the absence of a better alternative, but the median survival time is less than a year among patients with advanced-stage or metastatic disease. Pazopanib inhibits multiple receptor tyrosine kinases, including the tyrosine kinase coupled to the vascular endothelial growth factor receptor (VEGFR), thus inhibiting angiogenesis. It is authorised in the European Union for the treatment of advanced-stage renal carcinoma. Clinical evaluation of pazopanib is based on a double-blind placebo-controlled trial in 435 patients. Follow-up is currently too short to determine whether pazopanib improves overall survival. The median progression-free survival time, based on radiological criteria, was 5 months longer with pazopanib: 9.2 months versus 4.2 months with placebo. This is similar to the efficacy obtained in trials of other cytotoxic drugs such as sunitinib. The adverse-effect profile of pazopanib is unfavourable: it includes disorders linked to its antiangiogenic activity (hypertension, arterial thrombosis, myocardial infarction, haemorrhage, etc.), as well as gastrointestinal disorders and hand-foot syndrome. In clinical trials including a total of 593 patients, 2 patients receiving pazopanib developed torsades de pointes and 3 other patients died of liver failure. Numerous pharmacokinetic interactions are likely, notably involving cytochrome P450 isoenzyme CYP 3A4. The risk-benefit balance of pazopanib is currently too unfavourable to justify its use in patients with advanced-stage or metastatic kidney cancer.