Metastatic Renal Cell Cancer Therapeutic Options
Kidney cancer is one of the types of cancer that has a very poor response to chemotherapy.
The first immunotherapy drugs that were used 30 years ago were interferon and interlukin 2. The response rate was very poor, at or near 10%, with a very high toxicity profile.
Over the last 10 years numerous novel treatments have been developed and FDA-approved including targeted therapy, antiangiogenic inhibitors, monoclonal antibodies and immunotherapeutic agents, all with mechanisms of action very different from chemotherapy, and with a much improved toxicity profile.
Nexavar (sorafenib) and Sutent (sunitinib) were the first targeted tyrosine kinase inhibitors FDA-approved for metastatic renal cell cancer. By blocking RAF-kinase and having antiangiogenic properties these oral agents cause tumors to shrink. The major side effects associated with these drugs are diarrhea and hand foot syndrome.
Torisel (temserolimus) and Afinitor (everolimus) were subsequently FDA-approved. This class of drug is called mTOR inhibitors (inhibitors of the mammalian target of rapamycin kinase, which has an important role for cell growth). Torisel is given intravenously while Afinitor is an oral drug. Torisel requires pre-medication to avoid allergic reactions; diarrhea, swelling and pneumonia can also occur. Common side effects for Afinitor are diarrhea, rash, weight loss and nausea.
Votrient (pazopanib) and Inlyta (axitinib) were recently FDA-approved for stage IV renal cell cancer. They both have antiangiogenic properties and are kinase inhibitors. Votrient is oral and can cause nausea, diarrhea, changes in skin/hair, and weight loss.
The most common side effects for Inlyta (which is also oral) are diarrhea, fatigue, and loss of appetite. It is important to monitor renal function and blood pressure.
The monoclonal antibody Avastin (bevacizumab) was FDA-approved several years ago. It targets VEGF affecting the cancer vascularization. It is contradicted in patients with a history of CAD/MI, and blood pressure needs to be monitored. Avastin is administered intravenously every two weeks and in general is very well tolerated.
Opdivo (nivolumab) is a monoclonal antibody recently FDA-approved. The drug works by targeting the PDA-PDLI pathway, which is a protein present in some cancer cells and immune cells. It stimulates the immune system to destroy cancer cells. It is administered intravenously and the major side effects are immune mediated like colitis, pneumonitis, hepatitis or infusion reactions. In general it is extremely well tolerated with very significant response rates and durability of response.
Currently vaccine therapy and stem cell transplant are under investigation.