title: Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis.
abstract: Considering whole-brain radiotherapy (WBRT) for asymptomatic brain metastases can reduce performance status and delay systemic treatment, primary chemotherapy can be a feasible alternative treatment. Good and rapid response to epidermal growth factor tyrosine kinase inhibitor (EGFR TKI) treatment makes this an attractive option for never-smokers with adenocarcinoma of the lung. Between January 2005 and August 2007, 23 Korean never-smoking patients with adenocarcinoma of the lung who had synchronous asymptomatic brain metastasis were consecutively treated with EGFR TKI therapy, either gefitinib 250 mg or erlotinib 150 mg once daily, as first-line treatment after giving informed consent, until disease progression, unacceptable toxicity or patient's refusal. They have not received either any prior chemotherapy or any radiotherapy including stereotactic radiosurgery. Objective tumor responses were assessed 1 month after treatment and then every 2 months or when clinically indicated. Out of the 23 patients treated, 16 achieved a PR and 3 experienced stable disease (SD) while 4 experienced progressive disease (PD), resulting in a response rate of 69.6% and a disease control rate of 82.6%. Intracranial tumor responses were observed in 17 patients (73.9%). After a median follow-up of 21.8 months, the median progression-free and overall survival (OS) time was 7.1 and 18.8 months, respectively. Eleven patients received WBRT with a median time-to-local-treatment for intracranial tumors of 19.3 months. In conclusion, EGFR TKI treatment showed promising antitumor activity against both intracranial and extracranial tumors in chemotherapy-naïve never-smokers with adenocarcinoma of the lung. Therefore, these agents should be considered as the treatment of choice in this clinical setting.
authors.affiliation: Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Republic of Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Yunsuk
authors.initials: Y
authors.lastname: Choi
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.forename: Jung-Shin
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012074:Remission Induction; D012907:Smoking
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D000077156:Gefitinib