Renal cell carcinoma with an emphasis on drug therapy of advanced disease, part 1

The diagnosis, staging, and management of renal cell carcinoma (RCC) are reviewed. The mechanism, pharmacokinetics, toxicity, clinical activity, and application of molecularly targeted agents in RCC are emphasized.

RCC is the eighth most commonly diagnosed malignancy in the United States. The most common signs and symptoms are gross hematuria, flank pain, and the presence of a flank mass. Localized disease is found in about 55% of patients, 19% of patients have locally advanced disease, and 20% of patients have metastatic disease. Surgical resection is the mainstay of therapy for stage I-III RCC. The pharmacotherapy of RCC is undergoing significant change. Standard therapy used to include the cytokines interferon alfa and aldesleukin. High-dose aldesleukin is used to treat select patients. Its major value is the durability of responses in the few patients who achieve a complete remission. However, cytokines have been largely displaced by sorafenib tosylate, sunitinib malate, and temsirolimus due to their lower rates of toxicity and positive effects on progression-free survival. Bevacizumab has also shown activity in patients with advanced disease. Estimated five-year survival rates for patients with RCC are 89.6% for localized disease, 60.8% for regional disease, and 9.5% for patients with distant metastases. Studies are currently under way to assess the activity of combinations of available agents and new targeted agents as adjuvant therapy and for the management of advanced RCC.

The options available for the management of advanced RCC have expanded considerably in the past five years with the advent of molecularly targeted therapies.