June 5, 2004

Renal cell carcinoma (RCC) is the most common kind of kidney cancer. Unfortunately, most cases are not diagnosed until the cancer has spread to other parts of the body (metastasized), which means that patients with metastatic RCC usually have limited treatment options. Two new studies demonstrate that metastatic RCC responds to new drugs that target multiple, specific pathways in cancer cells.

In the first study, John Hainsworth, MD, Director of Clinical Research at the Sarah Cannon Cancer Center in Nashville, Tenn, and colleagues gave 62 patients with RCC a combination of bevacizumab (Avastin) and erlotinib (Tarceva). Of the first 40 patients who were treated, cancer in 25% of the patients showed a partial response at eight weeks, and the cancer progressed in only 12% of the patients. In addition, the cancer did not get worse for six months in 71% of patients. Usually, doctors only see a 5% response to treatment with the standard therapy—either interleukin-2 or interferon.

Dr. Hainsworth cautioned that these results are still preliminary. "If these results are verified in larger trials, this treatment may emerge as the first well-tolerated regimen for people with renal cancer."

These drugs are specifically designed to act on proteins important to the cancer process. Researchers think that erlotinib blocks an enzyme called the epidermal growth factor receptor tyrosine kinase, which regulates cancer cell growth. Bevacizumab is a monoclonal antibody that blocks the activity of a protein called vascular endothelial growth factor, which helps the tumor form new blood vessels in a process called angiogenesis.

Interestingly, these two drugs block different pathways in the cancer cell, and may lead to a new approach in using targeted therapy. "Combining these targeted agents is the future of cancer treatment," said Dr. Hainsworth. The U.S. Food and Drug Administration recently approved bevacizumab, but erlotinib is still an experimental drug and is only available through clinical trials at this time.

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In the second study, 63 patients with metastatic RCC received a new chemotherapy pill called SU011248. The cancer showed a partial response in nearly a quarter of the patients. Six months after treatment, the cancer was still not growing in 14 of those patients. At this point in the study, the new drug appears safe and well tolerated, although patients experienced mild to moderate fatigue and gastrointestinal problems.

"During the past 15 years, I have conducted many studies for renal cancer, but none of them showed this degree of activity as a single agent," said Robert J. Motzer, MD, the study's lead author and Attending Physician at Memorial Sloan-Kettering Cancer Center in New York City. "SU011248 clearly shows activity, is relatively well tolerated, and it's a pill that patients can take at home."

Researchers think that SU011248 blocks several different targets in cancer cells, including those necessary for cancer cell growth and new blood vessel formation (angiogenesis). SU011248 still needs to be tested in phase III clinical trials to confirm these findings.

"This is a very exciting drug for possible use in the treatment of renal cancer," added Dr. Motzer. "The disease has been considered 'the unbeatable cancer,' with resistance to all forms of chemotherapy and only a small proportion of patients responding to immunotherapies for a limited time."

What This Means for Patients

For the first time, there appears to be safer, more effective treatment options on the horizon for RCC. However, both studies, while promising, are small, phase II clinical trials, so investigators will need to compare these new drugs with the current standard therapy in phase III trials before these drugs become available outside of a clinical trial. So far, these results suggest two new ways of treating metastatic RCC. Both studies support the idea that blocking multiple molecular pathways in cancer cells is a reasonable approach in treating metastatic RCC and possibly other advanced cancers.