High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib.
BACKGROUND
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor that induces an early and dramatic response in 10% of patients with advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of disease recurrence after response have not been described.


METHODS
The authors evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1998 and 2002. They focused on patterns of disease recurrence, risk of brain metastases (BM) and leptomeningeal metastasis (LM), and long-term outcome after initial response to gefitinib.


RESULTS
Of the 139 patients treated with gefitinib, 21 (15%) achieved a partial response. The median age of the responders was 64 years (range, 38-87 years), the median Karnofsky performance score was 80 (range, 60-90), and 4 of the patients were men. All responders had adenocarcinoma. The central nervous system (CNS) was the initial site of disease recurrence in 7 (33%) patients (BM in 5 and LM in 2). In 9 (43%) patients, the initial site of disease recurrence was the lung and in 1 it was the liver and bone. Four (57%) of the patients with disease recurrence in the CNS had lung disease under control. BM also developed in 2 patients who had initial disease recurrence in the lungs. The actuarial 5-year incidence of CNS metastases was 60%. The median overall survival periods were 15 months and 23 months for patients with and without CNS metastases, respectively (P = 0.24).


CONCLUSIONS
The CNS was a frequent site of disease recurrence in patients with NSCLC after an initial response to gefitinib, regardless of disease control in the lungs. Patients should be carefully monitored for neurologic symptoms. Intrinsic resistance of metastatic clones, incomplete CNS penetrance of the drug, and longer survival are possible explanations for this high incidence.
Omuro
Antonio M P
AM
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Kris
Mark G
MG
Miller
Vincent A
VA
Franceschi
Enrico
E
Shah
Neelam
N
Milton
Daniel T
DT
Abrey
Lauren E
LE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000556:secondary*; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D017211:Treatment Failure
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib