The results of a phase III, randomized clinical study involving patients with advanced renal cell carcinoma and poor prognostic features show temsirolimus improved overall survival when compared to the current treatment for this stage of disease.
The study, led by Gary R. Hudes, M.D., director of the Genitourinary Malignancies Program at Fox Chase Cancer Center, is published in the May 31 issue of the New England Journal of Medicine.
A total of 626 patients with renal cell carcinoma (RCC) were enrolled in the study and received one of three treatments , a new drug called temsirolimus, an older drug called interferon, or both the new and old drugs together. The patients who received temsirolimus alone survived longer than those who received interferon, the usual or , standard, treatment for this disease.
"This is the first study to show that a new drug can improve overall survival for patients with metastatic renal cell cancer," said Hudes.
Patients who received both drugs - temsirolimus and interferon - did not appear to live longer than those given interferon. Hudes said this finding could be explained by the lower dose of temsirolimus given to patients who received the combination treatment.
Renal cell carcinoma (RCC) is the most common type of kidney cancer. Approximately 90 percent of the 51,190 new cases of kidney cancer diagnosed this year will be RCC. Although many patients with kidney cancer are cured by surgery that removes the tumor, approximately 35 percent of patients will experience a recurrence of their cancer or will have spread (metastasis) of their cancer to other organs.
"For these patients, the goal of treatment is to prevent further spread and growth of the cancer, and ideally, to reduce that amount of cancer," Hudes said. "Until recently, physicians lacked effective drugs to control the disease."
In the current study, the greatest increase in median survival was observed in patients randomized to receive temsirolimus (49 percent) compared with patients treated with interferon only. Patients treated with temsirolimus and interferon combined had a 15 percent increase in median survival compared with interferon alone. The median survival for temsirolimus alone was 10.9 months compared with and 8.4 months for the temsirolimus and interferon, and 7.3 months for the interferon.
"This is a modest improvement in survival but the patients in the study had the most advanced tumors," says Hudes. "It would be reasonable to hypothesize that temsirolimus could provide greater benefit to patients with less extensive metastatic disease. Only a randomized, clinical trial will give us that definitive knowledge."
Temsirolimus was better tolerated than interferon. Fewer patients treated with temsirolimus had grade 3 or 4 (severe) side effects compared with those treated with interferon or the combination of interferon and temsirolimus. Asthenia, anemia, nausea, dyspnea, and rash were the most common side effects associated with temsirolimus.
Temsirolimus (formerly known as CCI-779) blocks the function of the mammalian target of rapamycin (mTOR), a key protein within cells that regulates cell proliferation, growth and survival. Temsirolimus may also block angiogenesis, a process that tumors use to create a blood supply to maintain their growth.
In November 2006, Wyeth filed an application with the U.S. Food and Drug Administration for approval to market temsirolimus (brand name Torisel) for the treatment of advanced renal cell carcinoma. A decision on approval is expected before July 2007.