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19.02.2014:  RENAL CELL CANCER: MODERN DRUG THERAPY

Advanced renal cancer is the typical cancer type in which targeted treatment is the only effective treatment. Chemotherapy is mostly ineffective. The role of immunotherapy with the use of Interleukin-2 is now limited to very few patients. There are two groups of approved targeted agents for metastatic renal cancer.
1) Vascular Endothelial growth factor (VEGF) – directed therapies
2) Inhibitors of the mammalian target of rapamycin (mTOR)

Anti – VEGF
Anti – VEGF directed agents include the monoclonal antibody bevacizumab, the tyrosine kinase inhibitors (TKIs) sunitinib, pazopanib, sorafenib and axitinib.

Bevacizumab
Bevacizumab is given together with Interferon-a as first line treatment in advanced clear cell renal cancer. It is given intravenously usually every three weeks. The main side effects are hypertension, bleeding. The concomitant use of Interferon-a may induce fever, headache, asthenia and loss of appetite.

Sunitinib
Sunitinib is given as first line treatment in metastatic renal cell carcinoma. It is given as a pill orally for 4 weeks continuously followed by 2 weeks of rest. The main side effects are weakness, stomatitis, nail changes, thyroid dysfunction, hypertention, dry skin, diarrhea and decreased blood counts.

Pazopanib
Pazopanib is given as first line treatment or following Sunitinib failure. It is given orally continuously. The main side effects are stomatitis, diarrhea, hypertention, dry skin. It seems to be better tolerated than Sunitinib.

Sorafenib
Sorafenib is given as second line therapy following TKIs resistance. It is given orally continuously. The main side effects are weakness, hypertention, diarrhea, skin changes especially in hands and foot, decreased blood phosphorum, etc.

Axitinib
Axitinib is the newest TKI and is given following failure of Sunitinib or Pazopanib as second line targeted treatment in advanced renal carcinoma. It seems to be better than Sorafenib in terms of cancer progression interval. It is given orally continuously and the dose is adjusted based on the liver function. The main side effects are hypertention, weakness, loss of appetite, thyroid dysfunction, skin changes especially in hands and foot, diarrhea.

m-TOR inhibitors 
m-TOR inhibitors approved for advanced renal cell carcinoma include everolimus and temsirolimus.

Everolimus
Everolimus has been evaluated in patients with clear cell renal carcinoma who have been exposed previously to TKIs. It is given as a pill orally every day as a second or third line treatment.  The main side effects include mucositis, stomatitis, pneumonitis, skin rash, elevated blood sugar and triglycerides.

Temsirolimus
Temsirolimus is an intravenously given m-TOR inhibitor, principally, to patient with poor risk cancer who have not received any treatment in the past. The main side effects are the same with everolimus.