Targeted Drugs Slow Kidney Cancer

Drugs That Target a Tumor's Blood Supply May Help Treat Advanced Kidney Cancer

By Salynn Boyles
WebMD Health News

Reviewed By Louise Chang, MD
on Wednesday, January 10, 2007


Jan. 10, 2007 -- Drugs that target blood vessels that feed tumors are showing promise in the treatment of advanced kidney cancer.

Two studies published in the latest issue of The New England Journal of Medicine represent a "major step forward" in kidney cancer treatment, a leading researcher in the field tells WebMD.

The studies offer some of the best evidence yet that therapies that target the tumor blood supply -- known as antiangiogenesis drugs -- have a role to play in cancer treatment, says James Brugarolas, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas.

Researchers evaluated the oral drugs sunitinib and sorafenib. The drugs target the blood supply of the tumor and tumor growth.

"Just a few years ago, we only had one highly toxic drug approved for the treatment of this cancer," says Brugarolas, who did not participate in the two trials. "We now have these new treatments that arise from our understanding of the biology of this cancer."

The two new drugs did not cure patients of their disease, and it is not yet clear if they help keep patients alive longer than traditional drug therapies.

But both drugs appeared to slow tumor growth by several months in patients who participated in the two studies.

Particularly Deadly Cancer

An estimated 39,000 Americans are diagnosed with kidney cancer each year, and 13,000 people die of the disease, according to the American Cancer Society.

Surgery is the treatment of choice for localized disease, but in well over half of cases the tumor has either spread beyond the kidneys at diagnosis or the cancer recurs following surgery.

For many years, the toxic therapies interferon alfa or interleukin-2 have been the only available treatments for advanced renal kidney cancer, but they work for only a small percentage of patients.

As a result, the estimated five-year survival rate for patients with advanced kidney cancer is less than 10%, according to the National Cancer Institute.

These drugs help prevent tumor growth and target the tumor's blood supply. Both sunitinib and sorafenib have been approved by the FDA for the treatment of advanced kidney cancer.

The brand name of sunitinib is Sutent; it's made by Pfizer. The brand name of sorafenib is Nexavar; it's made by Bayer Healthcare. Both are WebMD sponsors.

The Sunitinib Findings

The newly reported sunitinib trial included 750 previously untreated patients with advanced kidney cancer. About half of the patients were treated with a standard course of the oral drug and about half received a standard course of interferon alfa.

Researchers reported that the median time it took tumors to grow, known as disease-free progression, was more than twice as long in the sunitinib-treated patients than in those treated with interferon -- 11 months vs. five months.

And 31% of the patients on the newer drug had improvements from treatment -- as seen on radiologic imaging -- compared with just 6% of the interferon-treated patients. As a group, the sunitinib patients also reported significantly better overall quality of life than the patients treated with interferon.

Researcher Robert J. Motzer, MD, of New York's Memorial Sloan-Kettering Cancer Center, tells WebMD that it is still not clear if treatment with sunitinib keeps patients alive longer, but he adds that there is good reason to believe that it does.

"You would expect that more than a doubling in disease-free survival would translate into longer overall survival, but we can't say that yet," he says.

The Sorafenib Study

Unlike the patients in Motzer's trial, those in the sorafenib study had already been treated, mostly with either interferon alfa or interleukin-2. All were considered treatment resistant.

Half of the 903 study participants received sorafenib and the other half received placebo.

Compared with placebo-treated patients, patients treated with sorafenib also had longer median progression-free survival (5.5 months vs. 2.8 months), and a higher response rate (10% vs. 2%).

There was a greater incidence of toxic side effects in the sorafenib-treated patients. The most commonly reported toxicities were diarrhea, rash, fatigue, and unpleasant skin reactions in the hands and feet. Serious adverse events included heart problems in 12 patients and hypertension.

In the study by Motzer and colleagues, just under a third of patients reduced their dosage of the antiangiogenesis drug due to these toxicities.

Motzer says the next step for researchers is to determine if responses improve when sunitinib, sorafenib, and similar therapies are given in combination.

"For many years, kidney cancer has been considered to be among the most treatment-resistant cancers," he says. "In the past there has been little hope for success with any treatment, but these drugs are changing that."

SOURCES: Motzer, R.J. and Escudier, B. The New England Journal of Medicine, Jan. 11, 2007; vol 356: pp 115-134. Robert J. Motzer, MD, attending physician, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York City. James Brugarolas, MD, University of Texas Southwestern Medical Center, Dallas.

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