Renal Cell Cancer Therapeutic Options
For the longest time interlukin-2 and interferon were the only options for advanced stage renal cell cancer. These two drugs had a very low response rate and a very high rate of side effects. In fact, high dose interlukin-2 was administered in the hospital in the ICU because it required ventilator support and vasopressors.
Since 2005, with an increased understanding of the molecular pathways implicated in the growth of renal cell cancer, there has been the development of numerous new drugs and the subsequent approval of six systemic targeted therapies. The first drugs approved were the tyrosine kinase inhibitors called sorafenib (Nexavar) and sunitinib (Sutent). The M-TOR inhibitors followed with temsirolimus (Torisel) and everolimus (Afinitor). Antiangiogenic bevacizumab (Avastin) was approved as well in combination with other therapies and most recently a new TKI inhibitor was FDA approved called pazopanib (Votrient). All of these drugs have an impact on a patient's survival.
Sorafenib (Nexavar) was the first tyrosine kinase inhibitor approved for advanced renal cell cancer. It is an oral multikinase inhibitor that inhibits pathways that promote tumor growth. The major side effects are dermatologic and gastrointestinal. It is taken orally twice a day. Sunitinib (Sutent) was FDA approved one year later and it is also a multikinase inhibitor, which is orally taken for four weeks on and two weeks off. Sunitinib is also well tolerated with major side effect being dermatologic, gastrointestinal and thyroid dysfunction.
Temsirolimus (Torisel) is not as convenient as the previous two drugs being intravenous on a weekly basis. The most common side effects are related to glucose tolerance and hyperlipidemia, and precautions for hypersensitivity reactions are recommended. Most patients tolerate Torisel very well.
Everolimus is an M-TOR inhibitor as well but it is oral making it more convenient. The major side effects are rash, mucositis and anorexia. Patients who progressed on sunitinib and sorafenib had a good response with everolimus. Bevacizumab is a monoclonal antibody with antiangiogenic properties, which prevents the growth of new blood vessels needed for the tumor growth and metastases. It is usually combined with other agents for example interferon 2. Avastin is contraindicated in patients with CAD and gastrointestinal bleeding, the blood pressure needs to be monitored closely otherwise the drug has no side effects.
The most recent FDA approved drug for metastatic renal cell is the multikinase inhibitor pazopanib (Votrient). Pazopanib is also oral and the most common side effects are diarrhea, HTN and anorexia. Renal cell cancer is the third most commonly diagnosed genitourinary malignancy and the eighth most commonly diagnosed malignancy in the U.S. Twenty percent of patients diagnosed with renal cell cancer have metastatic disease and the better understanding of the biology of the disease resulted in the development of new drugs, the majority of which are oral and have had a very significant impact on disease free survival as well as overall survival.