In the USA, kidney cancer is the sixth leading cause of cancer deaths, and is thought to be responsible for nearly 13 000 deaths a year. Kidney cancer is not a single disease, but is made up of several different types of cancer, each of which has different histological features, has a different clinical course, and responds differently to treatment. The most common type is clear-cell renal cancer, which accounts for 75% of patients. Treatment options are limited and survival is poor, and responses with use of chemotherapy, hormonal, or biological treatment, and even with some of the new targeted drugs, seldom exceed 10%.

Professor Olivier Rixe (University of Paris, France) and colleagues report findings from a phase II trial of axitinib -- a selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 -- in 52 patients with cytokine-refractory, metastatic kidney cancer (51 of whom had clear-cell renal cancer). 23 patients had complete or partial responses, some of which were long-lasting: 12 of these patients progressed during the study, with a duration of response ranging from around 4 months to 26 months. Additionally, 22 patients showed stable disease for longer than 8 weeks, including 13 patients with stable disease for 24 weeks or longer. Four patients had early disease progression. 30 patients had hypertension related to the treatment, but side-effects in general were manageable and controlled by dose modification or supportive care.

Selectively targeting a single growth factor receptor pathway could provide the potential to rationally adjust dosages and combine drugs directed at specific parts of the pathway to minimise toxicity and achieve the optimum therapeutic benefit. Professor Rixe concludes that "The objective response and time to progression in our study suggest that axitinib might be a promising drug in the treatment of patients with metastatic renal-cell cancer; although a randomised controlled trial is needed to confirm this finding."

In an accompanying Reflection and Reaction comment, Dr W Marston Linehan (National Cancer Institute, Bethesda, MA, USA) states that these findings "suggest that a drug such as axitinib has promise as a second-line treatment in cytokine-refractory metastatic renal-cell carcinoma, and might have potential as first-line treatment or in combination with other agents targeting the Von Hippel-Lindau pathway (or both)."


SOURCE: The Lancet Oncology

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