Lay Summary: Velcade, a myeloma drug, has activity in kidney cancer
Few treatment options exist for the patient with metastatic RCC. The majority of patients with metastatic RCC will die from their disease within 12 to 16 months of diagnosis, despite treatment with standard immune modulation. New agents with novel mechanisms are urgently needed for this clinical situation. Laboratory and preclinical studies have identified the proteasome as a potential target in solid tumor therapy , and this unique mechanism suggested that PS-341 may be efficacious in patients with RCC refractory to other therapies. There was a small phase II trial of PS-341 in patients with metastatic RCC. This study was closed after a planned analysis revealed only one objective response. These observations suggest that a subset of patients with RCC may be responsive to proteasome inhibition. Unfortunately, have been dissapointing with that study having one response in 21 patients. In a similar study from the Memorial Sloan-Kettering Cancer Institute, four of 37 patients with metastatic RCC responded to PS-341. Of the 37 assessable patients, the best response was a partial response in four patients (11%; 95% CI, 3% to 25%) and stable disease in 14 patients (38%; 95% CI, 23% to 55%). The four patients with partial response experienced response durations of 8, 8+, 15+, and 20+ months.
Drucker BJ, Schwartz L, Bacik J, et al: Phase II trial of PS-341 shows response in patients with advanced renal cell carcinoma. Proc Am Soc Clin Oncol 22:386, 2003 (abstr 1550)
Nancy B. Davis, David A. Taber, Rafat H. Ansari, Christopher W. Ryan, Christopher George, Everett E. Vokes, Nicholas J. Vogelzang, Walter M. Stadler Phase II Trial of PS-341 in Patients With Renal Cell Cancer: A University of Chicago Phase II Consortium Study Journal of Clinical Oncology, Vol 22, No 1 (January 1), 2004: pp. 115-119
G. Varuni Kondagunta, Beverly Drucker, Lawrence Schwartz, Jennifer Bacik, Stephanie Marion, Paul Russo, Madhu Mazumdar, Robert J. Motzer Phase II Trial of Bortezomib for Patients With Advanced Renal Cell Carcinoma Journal of Clinical Oncology, Vol 22, No 18 (September 15), 2004: pp. 3720-3725