Advanced Non Small Cell Lung Cancer
With increasing knowledge of the molecular changes occurring in cancer cells the development of targeted therapies has revolutionized cancer care, producing drugs that are more effective and less toxic than traditional chemotherapeutic agents.
The knowledge that cancer cells must produce new blood vessels in order to continue growing led to the development of an antiangiogenic therapy called bevacizumab (avastin). Avastin in combination with chemotherapy has improved overall survival in stage IV lung cancer patients. Blood pressure needs to be monitored closely since most patients tend to develop hypertension. The most serious side effects even though uncommon are bleeding, perforation of the bowel and cardiac problems. Avastin is contraindicated if the patient has hemoptysis or a history of coronary artery disease of gastrointestinal bleeding.
The EGFR (epidermal growth factor receptor) is a protein that regulates the growth of the cells. Some lung cancer cells have an overexpression of the EGFR enhancing the growth of the tumor. Several drugs have been developed which bind to the EGFR causing the arrest of tumor growth. Two of these EGFR inhibitors, erlotinib (tarceva) and afatinib (gilotrif), are in pill form, while cetuximab (erbitux) is intravenous. The most common side effects are rash and diarrhea. The rash correlates with efficacy of the drug it is therefore considered a “good sign” and it is treated with specific lotions, soaps and on occasion antibiotics.
Another more recent discovery is the presence in approximately 5% of non small cell lung cancers of the ALK mutation (anaplastic lymphoma kinase). This particular mutation has recently been targeted very successfully with a drug called crizotinib (xalkori) with a response rate of approximately 90%, unheard of in lung cancer. Crizotinib is a pill that is taken twice a day. The major side effects are nausea, vomiting and diarrhea.
The latest development that is currently not available is a monoclonal antibody that targets the PDL1 receptor. The preliminary results have been very impressive in heavily F-treated patients. Thankfully strides continue to be made.