Lung cancer is the commonest malignancy in the world accounting for about 1.2 million patients world over. Most of the patients present at an advanced stage. Chemotherapy prolongs life and gives symptomatic control in patients of advanced non-small cell lung cancer. The backbone of chemotherapy are the two platinum containing drugs, cisplatin and carboplatin. These are given as a two drug combination, the other drug being one of gemcitabine, pemetrexed, docetaxel, paclitaxel or vinorelbine. Half the treated patients will survive for 8-10 months, less than 10% of the patients survive 5 years.
Growth factors act via receptors to promote cell growth. Binding of the factor to the receptor switches on the receptors and induces cell division. When the growth factor dissociates from the receptor, the receptor is switched off and cell growth stops. Cancer is a disease resulting from mutations in growth promoting genes. Mutations that switch on the growth factor receptor gene permanently are common in cancer. Such a receptor behaves like a faulty electric switch that can not be turned off. It continues to promote cell growth even if there is no growth factor present. Activating mutations of the epithelial growth factor receptor (EGFR) gene are seen in non-small cell lung cancer.
One of the landmarks in oncology has been the development of drugs that can switch off activated growth promoting genes. If conventional chemotherapy is like carpet bombing, the use of these drugs is like a sniper attack. Two drugs erlotinib and gefitinib, that can be administered orally, are able to switch off EGFR switched on by what are known as tyrosine kinase domain mutations. This results in the arrest of growth of lung carcinoma cells. Oncologists have learned the hard way that every drug that shrinks a tumour does not prolong life. What impact does therapy with gefitinib or erlotinib have on patients with advanced non-small cell lung cancer?
Results from the the North-East Japan Study Group suggests that gefitinib is better than chemotherapy for patients with non-small cell lung cancer who have tyrosine kinase domain mutations in EGFR. Progression was 70% less likely if such patients were treated with gefitinib compared to chemotherapy. Gefitinib is less likely to cause adverse effects than chemotherapy. Patients usually have rash. Patients who develop rash with anti-EGFR agents appear to have a better tumour response. The only serious side effect of the drug is interstitial pneumonitis which is very rare. Gefitinib along with erlotinib is an option for patients who harbour mutations in the tyrosine kinase domain of EGFR. For some reason a bulk of patients who have gefitinib sensitizing mutations are non-smoker Asian women with adenocarcinoma of the lung.