High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib Journal Article
| Authors: | Omuro, A. M. P.; Kris, M. G.; Miller, V. A.; Franceschi, E.; Shah, N.; Milton, D. T.; Abrey, L. E. |
| Article Title: | High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib |
| Abstract: | 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. © 2005 American Cancer Society. |
| Keywords: | adult; controlled study; aged; aged, 80 and over; middle aged; survival rate; treatment failure; major clinical study; antineoplastic agents; bone metastasis; brain neoplasms; cancer incidence; neoplasm staging; cohort studies; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; incidence; receptor, epidermal growth factor; central nervous system; liver metastasis; lung metastasis; meningeal neoplasms; gefitinib; brain metastasis; recurrent disease; quinazolines; long-term follow-up; nonsmall cell lung carcinoma; meningeal metastasis; disease recurrence; leptomeningeal metastasis |
| Journal Title: | Cancer |
| Volume: | 103 |
| Issue: | 11 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2005-06-01 |
| Start Page: | 2344 |
| End Page: | 2348 |
| Language: | English |
| DOI: | 10.1002/cncr.21033 |
| PUBMED: | 15844174 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 59" - "Export Date: 24 October 2012" - "CODEN: CANCA" - "Source: Scopus" |
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