Chemotherapy for renal cell carcinoma

Renal cell carcinoma is a chemotherapy,-resistant tumor; which, with common ly used cytotoxic agents, exhibit a only marginal response rate when modern objective response criteria are applied. No clear survival benefit for pat ients a treated with chemotherapy has yet been demonstrated, although most trials indicate that responding patients survive longer: Among the more com monly available cytotoxic agents vinblastine has been repeatedly reported t o achieve a 6 - 9 % objective response rate in irrespective of the mode of application. 5-Fluorouracil- and Floxuridin (FUDR)-based chemotherapy appea l to achieve response rates in the range of 5 - 8 % with slightly better,re sults when applied by chronomodulation schedules. Trials evaluating the rec ently licensed newer cytotoxic agents have shown no major, improvement for the treatment of metastatic renal cell cancer: Studies including the topois omerase ase I inhibitors irinotecan and topotecan are ongoing. The taxanes (paclitaxel, docetaxel) have demonstrated no significant activity and gemci tabine has been reported with responses in single patients. Recent treatmen t approaches based on the biology of renal cell carcinoma with an increased expression of the multiple drug resistance (MDR) phenotype (pgp 170) have used chemotherapy in combination with verapamil or cyclosporine derivates a s inhibitors of the MDR-mechanism. The disappointing results of these trial s indicate that MDR is not the only mechanism of chemotherapy-resistance in renal cell carcinoma. In conclusion, chemotherapy has a limited role in me tastatic renal cell carcinoma and vinblastine is considered the standard tr eatment. Strict evaluation of new agents acting independently fr om the MDR -mechanism is necessary in order to identify drugs with an impact in the pa lliative , treatment of advanced renal cell carcinoma. of about 2 % worldwi de (1). Approximately one third of patients with renal cell carcinoma have metastatic or locally advanced disease at the time of initial presentation, and additionally 30 - 50 % of the rest will develop metastic disease (2,3) . Advanced renal cell carcinoma is characterized by a high level of resista nce to currently available systemic treatment modalities.