There have been two announcements in the press since December 2005 that certainly sound like we are getting closer to a drug that might help us with VHL.

Nexavar (Bayer) and Sutent (Pfizer) have both been approved for use with advanced kidney cancer – after it has spread to other areas of the body.

Most people with VHL don’t have kidney cancer that has spread. Are these new drugs for us or not? Should we try them at earlier stages of kidney cancer? If we take them for several weeks or months, what happens when we go off the drug? Is it okay to take it for years? How will we pay for access to these expensive new drugs? Are there better approaches?

The Renal SPORE (see footnote) at Dana Farber/Harvard Cancer Center sponsored a continuing medical education event for urologists, oncologists, and oncology nurses on April 7, 2006, in Boston. They presented their latest findings in the biology of renal cancer, approaches to treatment, new anti-angiogenic drugs, and the projects they have under way to further understand renal cancer and find better paths to a cure.

Germline VHL mutations -- the inheritable kind we deal with in our community -- represents only 4-5% of all kidney cancer in the general population. But among all kidney cancer tumors, 75% of kidney cancer is “clear cell renal cancer” (the same kind we see in VHL) and in fact the VHL gene loss is a primary cause of more than 60% of those tumors. These patients did not inherit a flaw in the VHL gene, but something happened to disable the gene’s function within the kidney, and a kidney tumor grew.

That puts VHL research right on the primary pathway for study of kidney cancer in general. As Dr. William Kaelin told the group, loss of the VHL protein plays a role in the maintenance of a kidney cancer tumor, not just its initiation. “If you fix VHL in the tumor, you can fix the tumor.”

With the larger market in view, the drug companies are working first on getting drugs approved for kidney cancer in general. But we are watching this work closely because of the intimate relationship between VHL and kidney cancer. If we find a drug that works for kidney cancer, it might also work for hemangioblastomas or pheochromocytomas.

Another area of investigation is an effort to find biomarkers – measurements of elements in blood or urine – that might indicate a suspicion of kidney cancer activity. The PSA for prostate cancer is a good example of a biomarker. If a man’s PSA level is elevated, there is need for further tests to determine whether prostate cancer is present, and to discuss opportunities for early treatment.

In the same way, if a doctor were able to do a simple test in the course of a regular examination and find an indicator that further tests for kidney cancer are warranted, then more people might be diagnosed at earlier stages. Currently, most people diagnosed with kidney cancer already have advanced disease. People with VHL at least have early warning that they might be at risk for kidney cancer, so we screen for it on a regular basis. But most people in the general population have no warning and no symptoms until the disease has spread to other parts of the body. Their only opportunity for an earlier diagnosis is what is called an “incidental finding” – a person is in an automobile accident, the doctors take an image to check the spleen, and they just happen to discover a suspicious mass on the kidney.

As of this writing, the best treatment options for people with VHL are (1) watchful waiting as outlined in the Handbook, (2) Radio Frequency Ablation or cryosurgery if these are possible or advisable, (3) partial nephrectomy when necessary. All of these have their risks. Today there are significant risks in the drugs as well. What we would love to have is a medical treatment (one or more drugs) that would control the growth of these tumors and keep them from advancing to cancer. Ideally, existing tumors might shrink.

Today, these drugs are all investigational for VHL. There is still no silver bullet. We need to learn more, and we can learn best through controlled studies called Clinical Trials. Several physicians are putting together clinical trials with some of these drugs specifically designed for people with VHL.

Dr. Othon Iliopoulos at the Mass. General Hospital in Boston
Dr. Eric Jonasch at the M.D. Anderson Cancer Center in Houston - OPEN May 06
Dr. Stéphane Richard, the French National Cancer Institute program on kidney cancer.

None of these trials is quite open at this moment, but they are expected to open within the next few months. We will post the details as they become available at http://www.vhl.org/trials.

There will be more drugs. Some people will respond better to one than another. Some drugs will be more specific for VHL, some will be more effective for VHL. The side effects will vary. Nonetheless, it is good to see so much interest in studying VHL, and so much good progress along the pathway toward a cure for VHL.

As printed in the VHL Family Forum 14:1, April/May 2006. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.