Targeted therapies for colorectal cancer

As researchers have learned more about the gene and protein changes in cells that cause cancer, they have been able to develop newer drugs that specifically target these changes. These targeted drugs work differently from standard chemotherapy drugs. They often have different (and less severe) side effects. At this time, they are most often used either along with chemotherapy or by themselves if chemotherapy is no longer working.

Bevacizumab (Avastin^®): Bevacizumab is a man-made version of a type of immune system protein called a monoclonal antibody. This antibody targets vascular endothelial growth factor (VEGF), a protein that helps tumors form new blood vessels to get nutrients (a process known as angiogenesis). Bevacizumab is most often used with chemotherapy drugs to treat advanced colorectal cancer.

Bevacizumab is given by intravenous (IV) infusion, usually once every 2 or 3 weeks. Bevacizumab has been shown to help improve survival for advanced cancers when added to chemotherapy, but it can also add to the side effects. Rare but possibly serious side effects include blood clots, severe bleeding, holes forming in the colon (called perforations), heart problems, and slow wound healing. If a hole forms in the colon it can lead to severe infection and may require surgery to correct. More common side effects include high blood pressure, tiredness, bleeding, low white blood cell counts, headaches, mouth sores, loss of appetite, and diarrhea.

Cetuximab (Erbitux^®): This is a monoclonal antibody that specifically attacks the epidermal growth factor receptor (EGFR), a molecule that often appears in high amounts on the surface of cancer cells and helps them grow.

Cetuximab is used in metastatic colorectal cancer, either as part of first-line treatment or after other treatments have been tried. Most often it is used either with irinotecan or by itself in those who can't take irinotecan or whose cancer is no longer responding to it.

About 4 out of 10 colorectal cancers have mutations (defects) in the KRAS gene, which make this drug ineffective. Doctors now commonly test the tumor for this gene change and only use this drug in people who do not have the mutation. Doctors may also test for a mutation in the BRAF gene, which would also indicate that cetuximab would not be effective.

Cetuximab is given by IV infusion, usually once a week or every other week. A rare but serious side effect of cetuximab is an allergic reaction during the first infusion, which could cause problems with breathing and low blood pressure. You may be given medicine before treatment to help prevent this. Many people develop skin problems such as an acne-like rash on the face and chest during treatment, which in some cases can lead to infections. Other side effects may include headache, tiredness, fever, and diarrhea.

Panitumumab (Vectibix^®): Panitumumab is another monoclonal antibody that attacks colorectal cancer cells. Like cetuximab, it targets the EGFR protein. It is used to treat metastatic colorectal cancer, usually after other treatments have been tried.

As with cetuximab, this drug is not effective in the 4 out of 10 people with colorectal cancers who have mutations in the KRAS gene. Most doctors now test the tumor for the KRAS mutation and only use this drug in people who do not have the mutation. Doctors may also test for a mutation in the BRAF gene, which would also indicate that this drug would not be effective.

Panitumumab is given by IV infusion, usually once every 2 weeks. Most people develop skin problems such as a rash during treatment, which in some cases can lead to infections. Other possible serious side effects are lung scarring and allergic reactions to the drug. Sensitivity to sunlight, fatigue, diarrhea, and changes in fingernails and toenails are also possible.