Clinical aspects of epidermal growth factor receptor inhibitors: benefit and risk.
Gefitinib and erlotinib are small molecules that selectively inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. Developmental studies of either drug have failed to show synergistic effects when combined with cytotoxic drugs as the first line treatment in patients with advanced non-small cell lung cancer, but erlotinib has shown survival prolongation when compared with best supportive care in patients with recurrence. Female gender, adenocarcinoma histology and lack of smoking history are considered to be clinical factors predicting response. Being positive for EGFR mutations in exons 18-24 in cancer cells has a strong correlation with response. On the other hand, preceding idiopathic pulmonary fibrosis, male gender and history of smoking appear to be risk factors for EGFR tyrosine kinase inhibitor-induced interstitial lung disease in the Japanese population. Reports on these factors predicting response or risk for interstitial lung disease have attracted great interest in the relation between cancer genetics and drugs, as well as the relation between ethnicity and genetics. In clinical practice, EGFR tyrosine kinase inhibitor should be prescribed with careful consideration and it is essential to assess benefit and risk of the drug.
Kato
Tefurumi
T
Shien-Lab and Division of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. tkato@ncc.go.jp
Nishio
Kazuto
K
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib