Immune-based therapies target advanced renal cell carcinoma

Vancouver, British Columbia-Currently, more than 50 clinical trials are open in the United States for renal cell carcinoma, most of which are early-phase studies. Significantly, a handful of late-phase trials are still open. Some are showing promising results with newer immune-based and vaccine therapies for the treatment of advanced RCC, a disease for which definitive treatments are lacking.

Speaking here at the AUA Western Section annual meeting, Dr. Sokoloff described phase III adjuvant trials of three investigational agents for RCC: vitespen (Oncophage), WX-G250 (Rencarex), and BAY 43-9006 (also known as sorafenib). All three trials included similar patient populations: those with locally advanced T3 or T4 disease with regional lymph node involvement, as well as those with larger T2 lesions.

Treatment consisted of 4 weeks of weekly innoculations, then injection every other week until supply was depleted. In the first part of the phase III trial, 818 patients were randomized and 409 treated. Results should be due in the next year.

The second part of the trial consists of the same treatment: 4 weekly innoculations followed by injections every other week in 600 patients in the United States and Europe.

Dr. Sokoloff emphasized that the treatment regimen has been very well tolerated and that it can easily be performed by nurses in a clinic.

The study of WX-G250, a chimeric monoclonal antibody, is a placebo-controlled, randomized study to evaluate adjuvant WX-G250 versus placebo in patients at risk for cancer recurrence. It has a patient population similar to that of the vitespen trial: those with high-risk localized or locally advanced disease. After randomization, patients receive WX-G250 (26 weekly IV infusions) or placebo. The primary endpoint for this trial also is recurrence-free survival.

U.S. trials currently have open enrollment, Dr. Sokoloff said.

Encouraging phase III data

Sorafenib, an inhibitor of Raf kinase and vascular endothelial growth factor, showed promising safety and efficacy results in a large phase III trial reported at the 2005 American Society of Clinical Oncology annual meeting.

Researchers in the placebo-controlled study reported that disease progression was significantly delayed in patients who received sorafenib. Progression-free survival was doubled to a median value of 24 weeks in patients receiving the drug compared with 12 weeks for patients receiving placebo (p<.000001). More than 900 patients with advanced kidney cancer who had previously failed one prior systemic therapy have been randomized in the ongoing multinational study.

Sorafenib is currently available to U.S. patients with advanced kidney cancer through a treatment protocol known as the Advanced Renal Cell Carcinoma Sorafenib study. To be eligible, individuals may not have been previously treated with sorafenib.

Dr. Sokoloff said an appealing feature of the adjuvant trials has been outpatient dosing, which can be performed by a clinic nursing staff. Some required pathologic analysis can be accomplished by a hospital pathologist. Tumor processing is necessary for individualized vaccines such as vitespen, but it is straightforward.

"This is something any of us can do with any of our patients. We need to get involved in these trials and to inform our patients about their availability," he concluded.