Targeted Therapies For Colorectal Cancer
The increasing knowledge of the genetic and protein changes occurring in colorectal cancer has led to the development of targeted therapies which are very different from the traditional chemotherapeutic agents these targeted agents in addition to being very effective are also less toxic.
Colorectal cancers are routinely tested for the EGFR receptor (epidermal growth factor receptor) and if no mutation is detected meaning the receptor is “wild type” two monoclonal antibodies can be utilized called cetuximab (Erbitux) and panitumumab (Vectibix) to target the receptor. Erbitux is administered as an intravenous infusion given weekly while Vectibix is given intravenously every two weeks. The monoclonal antibodies bind to the EGFR receptor preventing the EGF from binding to it and therefore preventing tumor growth and metastatic spread.
The most common side effects from the EGFR inhibitors are rash and diarrhea. The occurrence of the rash correlates with efficacy of the drugs. Numerous lotion/soaps and antibiotics can be utilized to keep the rash under control and typically treatment is not interrupted. Less common but more serious side effects would be an allergic reaction to the drugs affecting breathing, and hypotension. Typically premedications are infused prior to treatment in order to avoid an allergic reaction.
VEGF (vascular endothelial growth factor) is typically unregulated in colorectal cancer and two very effective drugs developed in the last decade target this growth factor; the antiangiogenic bevacizumab (Avastin) and ziv-aflibercept (Zaltrap). These drugs prevent the formation of new blood vessels necessary to nourish cancer cells, therefore contributing to the cell death. The most common side effect linked to this drug, is hypertension therefore blood pressure needs to be monitored closely. Less common but much more dangerous side effects are bowel perforation or bleeding and a myocardial infarction. These drugs are contraindicated in patients with known coronary artery disease or a history of gastrointestinal bleeding.
Most recently a new kinase inhibitor name regorafenib (Stivarga) has been found to be effective in colorectal cancer. Stivarga blocks the kinase on the surface of the cancer cells that causes tumor proliferation. The great advantage of this drug is that it is in a pill form. The liver function needs to be monitored. Not common but severe side effects are perforations and bleeding.
Thanks to these new targeted agents the life expectancy of advanced stage colorectal cancer has greatly improved over the last decade.