Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis.
BACKGROUND
Leptomeningeal carcinomatosis (LC) is a detrimental complication of patients with non-small-cell lung cancer (NSCLC). The effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on the clinical outcome of these patients, particularly those with EGFR mutations, has not been studied yet.


METHODS
We searched the database for lung cancer patients diagnosed from 2003 to 2010 in one Asian medical center. NSCLC patients who also had LC diagnosed by either cytology or brain neuroimaging studies were identified. The treatments and clinical outcomes were reviewed.


RESULTS
Of 5526 lung cancer patients, we identified 212 (3.8%) NSCLC patients with LC. Most patients (88.7%) had adenocarcinoma histology, and 129 (60.9%) patients had been treated with at least one regimen of EGFR TKI before the diagnosis of LC. One hundred and twenty-four (58.5%) patients were treated with EGFR TKI, and 128 (60.4%) patients were treated with whole-brain radiation therapy (WBRT) after the diagnosis of LC. The median overall survival was 4.5 months (95% confidence interval, 3.5-7.3). Multivariate analysis suggested that EGFR TKI therapy, WBRT, and cytotoxic chemotherapy were independent predictors for longer survival. Mutational status of EGFR was evaluated in 101 patients, and 75 mutations (74.3%) were detected. Among the 75 patients with EGFR mutations, EGFR TKI therapy and cytotoxic chemotherapy after diagnosis of LC remained the independent factors predictive of extended survival in the multivariate analysis.


CONCLUSIONS
Treatment of LC with EGFR TKI, cytotoxic chemotherapy, or WBRT in selected patients is associated with prolong survival period. These treatment options, especially EGFR TKIs, should be studied in patients with EGFR mutation-positive NSCLC and LC.
*Department of Oncology, †Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; ‡Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan; §Department of Medical Imaging, ‖Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; and ¶Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Bin-Chi
BC
Liao
Jih-Hsiang
JH
Lee
Chia-Chi
CC
Lin
Ya-Fang
YF
Chen
Chin-Hao
CH
Chang
Chao-Chi
CC
Ho
Jin-Yuan
JY
Shih
Chong-Jen
CJ
Yu
James Chih-Hsin
JC
Yang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D055756:Meningeal Carcinomatosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors