By Vijay Gunuganti, MD
Kidney cancer, also known as renal cell carcinoma, strikes an estimated 40,000 patients in the United States each year, representing 2 to 3 percent of all cancers diagnosed annually. Most cases of kidney cancer arise from unknown causes, but smoking and high blood pressure are known risk factors of the disease. About one third to half will have metastasis at the time of diagnosis or after nephrectomy.
Recently, the FDA has approved two new drugs for the treatment of metastatic renal cell carcinoma – Sorafenib (Nexavar: Onyx-Bayer) and Sunitnib (SUTENT: Pfizer) in December 2005 and January 2006, respectively. The last time the FDA approved any treatment for this disease was in 1992, with Interleukin-2 .
Conventional chemotherapy has proven to be a weak weapon against kidney cancer, because the very cells that the drugs attack are programmed to handle toxic substances.
Typical treatment for kidney cancer is surgery, followed by use of the biologic therapy agents Interferon alfa or Interleukin-2. Both drugs are similar to substances naturally made by the body's immune system and work by boosting the defense system to help fight off or destroy cancer cells, which has always been a fairly weak way to affect tumors.
Sorafenib (Nexavar: Onyx-Bayer) was approved in December, 2005 after a large, placebo controlled randomized trial was shown to delay progression of kidney cancer. Sorafenib acts by inhibiting two proteins, one that boosts the growth of the cancer cells themselves (RAF kinase) and one that sustains blood vessels, which nourish the tumors (angiogenesis).
More than 900 patients with advanced kidney cancer, who had previously failed one prior systemic therapy, were randomized in a multi-national, placebo-controlled Phase III study. Participating patients were randomized to either 400 mg sorafenib or placebo twice daily.
In this study, as assessed by independent radiological review, the median progression-free survival rate in the sorafenib group was 24 weeks (6 months) compared with 12 weeks (3 months) for patients receiving placebo. In addition, 74 percent of people receiving the new biological therapy saw their tumors shrink or stabilize, compared to 20 percent of those taking the placebo. Side effects of this medication are generally well tolerated and include rash, increased blood pressure and blisters on the palms of the hands or soles of the feet.
Sunitnib (SUTENT: Pfizer) was approved in January 2006, based on two phase II trials enrolling 169 individuals, who showed progression free survival of 8.3 months and with objective response seen in 26 to 36 percent of patients who had failed prior Interferon treatment. The duration of response was six to 12 months. Sutent is a multi-targeted agent which inhibits several proteins responsible for tumor growth and angiogenesis-like vascular endothelial growth factor (VEGF, PDGFR and others).
In another Sunitinib study, researchers enrolled 750 patients (375 in each arm) and patients were randomly assigned to receive either Interferon (IFN-•) or Sunitinib. Patients who were treated with Sunitnib had longer progression-free survival than patients on Interferon. Median Progression-free survival assessed by third-party independent review was 47 weeks (11 months) for Sunitinib versus 25 weeks (6 months) for IFN-•. The objective response rate (maximum tumor shrinkage of more than 50 percent) was 25 percent for Sunitinib versus 5 percent for IFN-•. Patients treated with Sunitinib were somewhat more likely to experience diarrhea, high blood pressure and “hand-foot syndrome,” a condition characterized by tenderness and sensitivity in the hands and feet.
Another new target agent called Temsirolimus (Wyeth) was studied involving patients with advanced kidney cancer who were considered to have a poor prognosis. Temsirolimus is an agent that attacks mTOR, a protein that controls the molecular cascade required for cells to proliferate.
Although mTOR exists in all cells, it is overexpressed in cancer cells. Cancer researchers believe that by attacking this target in cancer cells the damage will be limited to the malignancy rather than healthy cells.
The 209 patients getting Interferon lived an average of 7.3 months after starting treatment, while the 207 patients on Temsirolimus survived 10.3 months. Another 210 patients received both agents in a combination therapy, but they fared only slightly better than those getting Interferon alone.
Despite these encouraging advancements, medical science has still got a long way to go. None of these drugs, to our knowledge, puts renal cancer in complete remission.
There is never a good time to have cancer, but this is clearly a promising time for treating kidney cancer patients, because in the last two months, two new drugs have been added to fight the disease, after having no new drugs approved since 1992.
It’s still unclear how long the effects of the drug last or whether patients will have to take the drug for the rest of their lives to maintain their benefits. Further, no one knows whether one of the newer treatments works better than the other, or whether treatment should be given immediately after surgery.
Vijay Gunuganti, MD is a Medical Oncologist who specializes in the treatment of kidney, bladder and prostate cancers in San Antonio and Bexar County.
