The current standard of care for advanced renal cell cancer is immunotherapy. But this form of treatment has had poor acceptance due to low response rate, short survival duration but significant toxicity. Though approved by US FDA, high dose interleukin-2 treatment will only benefit a very small group of patients who are able to tolerate the high toxicity profile of the treatment regimen.

Alternative forms of immunotherapy with interferon 2a and/or low dose interleukin-2 though more commonly applied due to lower toxicity have a dismal response rate. Recent trials with novel molecules has been greeted with great optimism and is summarized below:

Patients with advanced renal cancer with prior nephrectomy respond significantly better to low dose interferon 2a. This was proven in 2 phase III trials that exhibited a superior response rate and median survival (11-17 months vs 7-8.1 months) with interferon 2a in patients who underwent a nephrectomy as compared to those without surgery.

Angiogenesis is an important aspect of tumorigenesis and kidney cancer is the ideal tumour model for clinical trials targeting vascular growth. The loss of vonHippel Lindau gene in most renal cell cancer leads to neovascularisation that is the essence of tumour growth. Hence, novel targeted therapy, using antibody or small molecules that block the signalling pathway of neovascularisation are currently being intensely investigated.

In 2002, for the first time, bevacizumab, an anti-VEGF antibody, was shown to be able to double the progression free survival (PFS) of patients as compared to placebo. Currently, two phase III trials, one in US and one in Europe and Asia, are ongoing to investigate whether there is survival benefit combining bevacizumab and interferon 2a as compared to interferon 2a alone. In 2005, results of three other studies create further excitement:

First was the combination of bevacizumab with erlotinib, a EGFR antibody, with response rate of 25%, disease stabilization of 60% and a progression free survival (PFS) of 11 months. Sixty percent patients were still alive at 18 months.

Yet another small molecule, Sorafenib, which inhibits the activity of VEGF-receptor (VEGFR), significantly prolonged PFS (24 weeks vs 12 weeks) compared to placebo. Sutent, is another small molecule that targeted the VEGFR and in a recent report, induced the highest ever reported response rate of 40% in an advanced renal cell cancer trial.

Hence with so many new and promising compounds, this is an exciting time for renal cell cancer management although we are awaiting for the mature results of these clinical trials.

 

Tay Miah Hiang
Consultant
Medical Oncology
National Cancer Centre, Singapore