Medullary Renal Cell Carcinoma and Response to Therapy With Bortezomib

TO THE EDITOR: Metastatic non–clear cell renal carcinoma comprises several histologic subtypes, including medullary and collecting duct carcinoma. Medullary renal carcinoma is difficult to separate from collecting duct carcinoma morphologically, but has been diagnosed in patients with sickle cell disease or sickle cell trait. We previously reported a retrospective review of 64 patients with non–clear cell histology and found that patients had a median overall survival time of 9.4 months. Twenty-six (41%) of the 64 patients were identified with collecting duct or medullary pathology. These patients were treated with cytokine therapy or systemic chemotherapy. There were no responses to cytokine therapy. One of the patients with collecting duct/medullary carcinoma had a 5-month-long partial response to systemic chemotherapy. Median survival for the patients of the collecting duct subset was 11 months. Partial responses to systemic chemotherapy have been reported elsewhere, but are rare and of short duration. In the September 15, 2004, issue of the Journal of Clinical Oncology, we reported a phase II study evaluating bortezomib, a proteasome inhibitor, in patients with advanced renal cell carcinoma. Of 37 assessable patients, four patients achieved a partial response to therapy; three patients had clear cell histology and one patient had medullary carcinoma. We now report the updated follow-up of the medullary carcinoma patient. The patient received 7 months of bortezomib and achieved a complete response. He remains without evidence of disease after more than 27 months of follow-up. Metastatic non–clear cell renal carcinoma is a rare entity with a poor outcome. Given the small numbers, patients with non–clear cell renal carcinoma have not been well represented in clinical trials. Better molecular characterization will help to more accurately identify appropriate agents for this subset of patients. Further study of bortezomib in medullary renal carcinoma is indicated.