A unique targeted drug significantly extends the lives of patients with metastatic kidney cancer, bringing new treatment options to a disease once thought intractable, according to City of Hope researchers and colleagues.
Temsirolimus, a drug that disrupts important inner workings of cancer cells, helped patients live more than three months longer — a nearly 50 percent improvement — than did standard therapies, a multicenter research team reported in the May 31 issue of the New England Journal of Medicine. Results suggest the drug may become a first-line treatment for selected patients with metastatic kidney cancer.
“We’ve now found three new drugs since late 2005 that show promise against kidney cancer — a disease that has desperately needed better treatments,” said Robert A. Figlin, M.D., the Arthur and Rosalie Kaplan Professor of Medical Oncology at City of Hope and one of the study authors. “This is an exciting movement that shows the value of targeting therapy directly to cancer cells’ vulnerabilities.”
As Figlin explained, traditional, cell-killing chemotherapies have shown little success against renal cell carcinoma, the most common form of kidney cancer, so researchers had turned to immunotherapies to counter the disease. However, temsirolimus — directed at a novel new cancer target called mTOR — appears to be more effective than these immunotherapy drugs.
Temsirolimus inhibits what scientists call mammalian target of rapamycin (mTOR) kinase, an enzyme that plays a part in signaling inside a cell. Disrupting mTOR signaling suppresses proteins that not only help cancer cells develop and mature, but also recruit the tiny blood vessels that nourish tumors with blood. That is important, Figlin noted, because kidney cancer depends heavily on this blood vessel recruitment to survive.
“When we investigate the biology of these tumors and do the hard work to understand what fuels them, then we can attack them in a smarter, more strategic way,” said Figlin, associate director for clinical research at City of Hope Comprehensive Cancer Center.
Study investigators from nine nations enrolled 626 patients with previously untreated metastatic kidney cancer in the phase 3 randomized trial, called the Global Advanced Renal-Cell Carcinoma Trial. Patients were assigned to one of three groups: They received either 25 milligrams (mg) of injected temsirolimus weekly, injected interferon alfa three times a week, or a combination of 15 mg of temsirolimus and three injections of interferon alfa weekly.
Interferon alfa is a cytokine, a protein that activates the immune system. Research has shown the cytokine shrinks metastatic kidney cancer tumors in 5 to 20 percent of patients, so it has become a treatment option for those diagnosed with the disease. Study findings showed no significant survival benefit to combining temsirolimus with interferon alfa.
Interferon alfa also can cause a variety of serious side effects. In the study, patients on temsirolimus experienced fewer serious side effects than those on interferon alfa alone.
“These patients reported a better quality of life,” said Figlin, who chairs the Division of Medical Oncology & Therapeutics Research at City of Hope.
Other targeted drugs recently shown effective in large clinical trials against metastatic renal cell cancer include sorafenib and sunitinib. Thousands could benefit from improved drugs for kidney cancer, as nearly 39,000 new cases of the disease and 13,000 associated deaths were expected in the United States for 2006. Distant metastases develop in about a third of patients, and most of these cannot be cured.
The temsirolimus study’s lead author was Gary Hudes, M.D., medical oncologist at Fox Chase Cancer Center. The study was supported by Wyeth Research, part of Wyeth Pharmaceuticals, which is developing the drug.
