Medical treatment options in patients with metastatic renal cell carcinoma

Renal cell carcinoma (RCC) is a common urological tumour and accounts for 3% of all human malig- nancies. Each year in Europe 40 000 patients are newly diagnosed with RCC, and almost 20 000 people die of the disease. In the United States, in 2003, RCC accounted for 31 000 people diagnosed with the disease, 12 000 deaths, and was the 10th most common cause of cancer mortality in men (1). It is estimated that 25-30% of all patients with RCC have metastases at presentation, and even following complete resection of the primary tumour by radical nephrectomy, relapse occurs in 20-30% of patients. The overall 5-year survival rate is 60%. Those who present with meta- stases have a median survival of 6-12 months, with a 5-year survival of <10% (2). Renal cell carcinomas generally arise in the epithe- lium of the proximal tubule. Approximately 80% are of clear cell histology and 15% are papillary. Medical treatment options are generally offered for locally advanced or metastatic renal cell carcinoma, and much of the clinical experience with these approaches is in patients with clear cell histology. Chemotherapy Chemotherapy or radiation has only limited effects in metastatic RCC. A recent study reporting the effects of chemotherapy, published by Amato, reviewed more than 3 600 patients with metastatic RCC and demonstrated the highest response rates for vinblastine (mean objective remission rate: 6.67%), 5-fluorouracil (mean objective remission rate: 6.57%) and floxuridine (mean objective remission rate: 9.66%) (3). The impact of these cytotoxic agents is increased when combined with cytokine-based immunotherapies. In contrast, the combination of various chemotherapeutic agents (polychemotherapy) did not improve the antitumour effect compared with the monotherapies mentioned, whereas the side effects increased. The overexpression of multiple drug resistance genes (MDR, e.g. p-170), glutathione-S transferase and the down-regulation of topoisomerase-2 are mainly responsible for the meager effects of the cytotoxic therapy (3,4).