Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib.
BACKGROUND
The efficacy of high-dose (1250 mg/d) gefitinib for the treatment of leptomeningeal metastasis in a patient with lung cancer harboring a mutation in the epidermal growth factor receptor (EGFR) gene was previously reported. We speculate that erlotinib, instead of high dose of gefitinib, may be also effective for the treatment of central nervous system (CNS) lesions, as trough serum concentration of erlotinib is nine times higher than that of gefitinib.


METHODS
Patients with lung cancer in whom CNS lesions developed after an initial good response to gefitinib for extra CNS lesions were enrolled in the study. Tumor response, performance status, neurologic symptoms, and survival were retrospectively evaluated.


RESULTS
All seven patients had EGFR mutations in their primary tumors except one patient. The median interval between gefitinib withdrawal and erlotinib administration was 5 days. Three patients showed partial response, three had stable disease, and one had progressive disease. Performance status and symptoms improved in five patients. The overall survival from the initiation of erlotinib treatment ranged from 15 to 530 days (median, 88 days).


CONCLUSIONS
Erlotinib was a reasonable option for the treatment of CNS diseases that appeared after a good initial response of extra CNS disease to gefitinib.
Katayama
Tatsuya
T
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan.
Shimizu
Junichi
J
Suda
Kenichi
K
Onozato
Ryoichi
R
Fukui
Takayuki
T
Ito
Simon
S
Hatooka
Shunzo
S
Sueda
Taijiro
T
Hida
Toyoaki
T
Yatabe
Yasushi
Y
Mitsudomi
Tetsuya
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D013120:Spinal Cord Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib