CNS metastases in non-small-cell lung cancer: Current role of EGFR-TKI therapy and future perspectives

Lung Cancer

Volumn 80, Issue 3, 2013, Pages 242-248

  Berger, Lars Arne ^a   Riesenberg, Hendrik ^a   Bokemeyer, Carsten ^a   Atanackovic, Djordje ^a  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

Author keywords

Brain metastases; Epithelial growth factor receptor; Non small cell lung cancer; Tyrosine kinase inhibitors

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR;

BLOOD BRAIN BARRIER; BRAIN RADIATION; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER MORTALITY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER REGRESSION; CENTRAL NERVOUS SYSTEM METASTASIS; CEREBROSPINAL FLUID; CLINICAL DECISION MAKING; DISEASE COURSE; DRUG TOLERABILITY; GENE MUTATION; HUMAN; IC 50; LUNG NON SMALL CELL CANCER; MORBIDITY; PRIMARY TUMOR; PRIORITY JOURNAL; REVIEW; TREATMENT FAILURE; TREATMENT RESPONSE; TUMOR BIOPSY; WILD TYPE;

ANTINEOPLASTIC AGENTS; BLOOD-BRAIN BARRIER; CARCINOMA, NON-SMALL-CELL LUNG; CENTRAL NERVOUS SYSTEM NEOPLASMS; HUMANS; LUNG NEOPLASMS; PROGNOSIS; PROTEIN KINASE INHIBITORS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84877109191     PISSN: 01695002     EISSN: 18728332     Source Type: Journal    
DOI: 10.1016/j.lungcan.2013.02.004     Document Type: Review

References (93)

1. Bailon O., Chouahnia K., Augier A., Bouillet T., Billot S., Coman I., et al. Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma. Neuro Oncol 2012, 14(4):491-495.
2. Namba Y., Kijima T., Yokota S., Niinaka M., Kawamura S., Iwasaki T., et al. Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer 2004, 6(2):123-128.
3. Barlesi F., Gervais R., Lena H., Hureaux J., Berard H., Paillotin D., et al. Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01). Ann Oncol 2011, 22(11):2466-2470.
4. Markesbery W.R., Brooks W.H., Gupta G.D., Young A.B. Treatment for patients with cerebral metastases. Arch Neurol 1978, 35(11):754-756.
5. Benedettini E., Scholl L.M., Peyton M., Reilly J., Ware C., Davis L., et al. Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis. Am J Pathol 2010, 177(1):415-423.
6. Saad A.G., Yeap B.Y., Thunnissen F.B., Pinkus G.S., Pinkus J.L., Loda M., et al. Immunohistochemical markers associated with brain metastases in patients with nonsmall cell lung carcinoma. Cancer 2008, 113(8):2129-2138.
7. Grossman S.A., Krabak M.J. Leptomeningeal carcinomatosis. Cancer Treat Rev 1999, 25(2):103-119.
8. Omuro A.M., Kris M.G., Miller V.A., Franceschi E., Shah N., Milton D.T., et al. High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 2005, 103(11):2344-2348.
9. Clarke J.L., Perez H.R., Jacks L.M., Panageas K.S., DeAngelis L.M. Leptomeningeal metastases in the MRI era. Neurology 2010, 74(18):1449-1454.
10. Wasserstrom W.R., Glass J.P., Posner J.B. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 1982, 49(4):759-772.
11. Balm M., Hammack J. Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol 1996, 53(7):626-632.
12. Herrlinger U., Förschler H., Küker W., Meyermann R., Bamberg M., Dichgans J., et al. Leptomeningeal metastasis: survival and prognostic factors in 155 patients. J Neurol Sci 2004, 223(2):167-178.
13. Chuang T.Y., Yu C.J., Shih J.Y., Yang P.C., Kuo S.H. Cytologically proven meningeal carcinomatosis in patients with lung cancer: clinical observation of 34 cases. J Formos Med Assoc 2008, 107(11):851-856.
14. Chamberlain M.C., Kormanik P. Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy. Arch Neurol 1998, 55(4):506-512.
15. Glantz M.J., Cole B.F., Recht L., Akerley W., Mills P., Saris S., et al. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?. J Clin Oncol 1998, 16(4):1561-1567.
16. Morris P.G., Reiner A.S., Rosenvald-Szenberg O., Clarke J.L., Panageas K.S., Perez H.R., et al. Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 2012, 7(2):382-385.
17. Eichler A.F., Kahle K.T., Wang D.L., Joshi V.A., Willers H., Engelman J.A., et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol 2010, 12(11):1193-1199.
18. Lee D.H., Han J.Y., Kim H.T., Yoon S.J., Pyo H.R., Cho K.H., et al. Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first: result of a randomized pilot study. Cancer 2008, 113(1):143-149.
19. Shepherd F.A., Pereira J.R., Ciuleanu T., Tan E.H., Hirsh V., Thongprasert S., et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005, 353(2):123-132.
20. Thatcher N., Chang A., Parikh P., Pereira J.R., Ciuleanu T., von Pawel J., et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (iressa survival evaluation in lung cancer). Lancet 2005, 366(9496):1527-1537.
21. Lynch T.J., Bell D.W., Sordella R., Gurubhagavatula S., Okimoto R.A., Branningan B.W., et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004, 350(21):2129-2139.
22. Paez J.G., Jänne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004, 304(5676):1497-1500.
23. Soria J.C., Mok T.S., Cappuzzo F., Jänne P.A. EGFR-mutated oncogene-addicted non-small cell lung cancer: current trends and future prospects. Cancer Treat Rev 2012, 38(5):416-430.
24. Kim E.S., Hirsh V., Mok T., Socinski M.A., Gervais R., Wu Y.L., et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008, 372(9652):1809-1818.
25. Tsao M.S., Sakurada A., Cutz J.C., Zhu C.Q., Kamel-Reid S., Squire J., et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005, 353(2):133-144.
26. Hirsch F.R., Varella-Garcia M., Bunn P.A., Franklin W.A., Dziadziuszko R., Thatcher N., et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006, 24(31):5034-5042.
27. Schneider C.P., Heigener D., Schott-von-Römer K., Gütz S., Laack E., Digel W., et al. Epidermal growth factor receptor-related tumor markers and clinical outcomes with erlotinib in non-small cell lung cancer: an analysis of patients from german centers in the TRUST study. J Thorac Oncol 2008, 3(12):1446-1453.
28. Zhu C.Q., da Cunha Santos G., Ding K., Sakurada A., Cutz J.C., Liu N., et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008, 26(26):4268-4275.
29. Cappuzzo F., Hirsch F.R., Rossi E., Bartolini S., Ceresoli G.L., Bemis L., et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 2005, 97(9):643-655.
30. Cortes-Funes H., Gomez C., Rosell R., Valero P., Garcia-Giron C., Velasco A., et al. Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients. Ann Oncol 2005, 16(7):1081-1086.
31. Mitsudomi T., Kosaka T., Endoh H., Horio Y., Hida T., Mori S., et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 2005, 23(11):2513-2520.
32. Han S.W., Kim T.Y., Jeon Y.K., Hwang P.G., Im S.A., Lee K.H., et al. Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin Cancer Res 2006, 12(8):2538-2544.
33. Taron M., Ichinose Y., Rosell R., Mok T., Massuti B., Zamora L., et al. Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res 2005, 11(16):5878-5885.
34. Jackman D.M., Miller V.A., Cioffredi L.A., Yeap B.Y., Jänne P.A., Riely G.J., et al. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res 2009, 15(16):5267-5273.
35. Douillard J.Y., Shepherd F.A., Hirsh V., Mok T., Socinski M.A., Gervais R., et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol 2010, 28(5):744-752.
36. Mok T.S., Wu Y.L., Thongprasert S., Yang C.H., Chu D.T., Saijo N., et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009, 361(10):947-957.
37. Mitsudomi T., Morita S., Yatabe Y., Negoro S., Okamoto I., Tsurutani J., et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010, 11(2):121-128.
38. Maemondo M., Inoue A., Kobayashi K., Sugawara S., Oizumi S., Isobe H., et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010, 362(25):2380-2388.
39. Mok T.S., Wu Y.L., Yu C.J., Zhou C., Chen Y.M., Zhang L., et al. Randomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol 2009, 27(30):5080-5087.
40. Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E., et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012, 13(3):239-246.
41. Maheswaran S., Sequist L.V., Nagrath S., Ulkus L., Brannigan B., Collura C.V., et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008, 359(4):366-377.
42. Inukai M., Toyooka S., Ito S., Asano H., Ichihara S., Soh J., et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 2006, 66(16):7854-7858.
43. Cappuzzo F., Jänne P.A., Skokan M., Finocchiaro G., Rossi E., Ligorio C., et al. MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients. Ann Oncol 2009, 20(2):298-304.
44. Sequist L.V., Martins R.G., Spigel D., Grunberg S.M., Spira A., Jänne P.A., et al. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 2008, 26(15):2442-2449.
45. Yang C.H., Yu C.J., Shih J.Y., Chang Y.C., Hu F.C., Tsai M.C., et al. Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol 2008, 26(16):2745-2753.
46. Miller V.A., Hirsh V., Cadranel J., Chen Y.M., Park K., Kim S.W., et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012, 13(5):528-538.
47. Yang J.C.-H., Schuler M.H., Yamamoto N., O'Byrne K.J., Hirsh V., Mok T., et al. LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 2012, 30.. p. abstr LBA7500.
48. Matsumoto S., Takahashi K., Iwakawa R., Matsuno Y., Nakanishi Y., Kohno T., et al. Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 2006, 119(6):1491-1494.
49. Li Z., Lu J., Zhao Y., Gou H. The retrospective analysis of the frequency of EGFR mutations and the efficacy of gefitinib in NSCLC patients with brain metastasis. J Clin Oncol 2011, 29(15 suppl).
50. Lee Y.J., Park I.K., Park M.S., Choi H.J., Cho B.C., Chung K.Y., et al. Activating mutations within the EGFR kinase domain: a molecular predictor of disease-free survival in resected pulmonary adenocarcinoma. J Cancer Res Clin Oncol 2009, 135(12):1647-1654.
51. Lee Y.J., Choi H.J., Kim S.K., Chang J., Moon J.W., Park I.K., et al. Frequent central nervous system failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors in Korean patients with nonsmall-cell lung cancer. Cancer 2010, 116(5):1336-1343.
52. Heon S., Yeap B.Y., Britt G.J., Costa D.B., Rabin M.S., Jackman D.M., et al. Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res 2010, 16(23):5873-5882.
53. Chen A.M., Jahan T.M., Jablons D.M., Garcia J., Larson D.A. Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain. Cancer 2007, 109(8):1668-1675.
54. Ceresoli G.L., Reni M., Chiesa G., Carretta A., Schipani S., Passoni P., et al. Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment: risk factors analysis. Cancer 2002, 95(3):605-612.
55. Heon S., Yeap B.Y., Lindeman N.I., Joshi V.A., Butaney M., Britt G.J., et al. The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations. Clin Cancer Res 2012, 18(16):4406-4414.
56. Cappuzzo F., Ardizzoni A., Soto-Parra H., Gridelli C., Maione P., Tiseo M., et al. Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer 2003, 41(2):227-231.
57. Hotta K., Kiura K., Ueoka H., Tabata M., Fujiwara K., Kozuki T., et al. Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 2004, 46(2):255-261.
58. Ceresoli G.L., Cappuzzo F., Gregorc V., Bartolini S., Crinò L., Villa E. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 2004, 15(7):1042-1047.
59. Kim M.K., Lee K.H., Lee J.K., Choi J.H., Hyun M.S. Gefitinib is also active for carcinomatous meningitis in NSCLC. Lung Cancer 2005, 50(2):265-269.
60. Wu C., Li Y.L., Wang Z.M., Li Z., Zhang T.X., Wei Z. Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer 2007, 57(3):359-364.
61. Pan M., Santamaria M., Wollman D.B. CNS response after erlotinib therapy in a patient with metastatic NSCLC with an EGFR mutation. Nat Clin Pract Oncol 2007, 4(10):603-607.
62. Fekrazad M.H., Ravindranathan M., Jones D.V. Response of intracranial metastases to erlotinib therapy. J Clin Oncol 2007, 25(31):5024-5026.
63. Lai C.S., Boshoff C., Falzon M., Lee S.M. Complete response to erlotinib treatment in brain metastases from recurrent NSCLC. Thorax 2006, 61(1):p91.
64. Chiu C.H., Tsai C.M., Chen Y.M., Chiang S.C., Liou J.L., Perng R.P. Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity. Lung Cancer 2005, 47(1):129-138.
65. Shimato S., Mitsudomi T., Kosaka T., Yatabe Y., Wakabayashi T., Mizuno M., et al. EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol 2006, 8(2):137-144.
66. Kim J.E., Lee D.H., Choi Y., Yoon D.H., Kim S.W., Suh C., et al. 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. Lung Cancer 2009, 65(3):351-354.
67. Park S.J., Kim H.T., Lee D.H., Kim K.P., Kim S.W., Suh C., et al. Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation. Lung Cancer 2012, 77(3):556-560.
68. Popat S., Hughes S., Papadopoulos P., Wilkins A., Moore S., Priest K., et al. Recurrent responses to non-small cell lung cancer brain metastases with erlotinib. Lung Cancer 2007, 56(1):135-137.
69. Jackman D.M., Holmes A.J., Lindeman N., Wen P.Y., Kesari S., Borras A.M., et al. Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol 2006, 24(27):4517-4520.
70. Ruppert A.M., Beau-Faller M., Neuville A., Guerin E., Voegeli A.C., Mennecier B., et al. EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up. Eur Respir J 2009, 33(2):436-440.
71. Clarke J.L., Pao W., Wu N., Miller V.A., Lassman A.B. High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neuro Oncol 2010, 99(2):283-286.
72. Sun M., Behrens C., Feng L., Ozburn N., Tang X., Yin G., et al. HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res 2009, 15(15):4829-4837.
73. Burel-Vandenbos F., Ambrosetti D., Coutts M., Pedeutour F. EGFR mutation status in brain metastases of non-small cell lung carcinoma. J Neurooncol 2013, 111(1):1-10.
74. McKillop D., Partridge E.A., Kemp J.V., Spence M.P., Kendrew J., Barnett S., et al. Tumor penetration of gefitinib (Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor. Mol Cancer Ther 2005, 4(4):641-649.
75. Neville K., Parise R.A., Thompson P., Aleksic A., Egorin M.J., Balis F.M., et al. Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to nonhuman primates. Clin Cancer Res 2004, 10(7):2525-2529.
76. Jamal-Hanjani M., Spicer J. Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Clin Cancer Res 2012, 18(4):938-944.
77. Weber B., Winterdahl M., Memon A., Sorensen B.S., Keiding S., Sorensen L., et al. Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. J Thorac Oncol 2011, 6(7):1287-1289.
78. Yi H.G., Kim H.J., Kim Y.J., Han S.W., Oh D.Y., Lee S.H., et al. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI. Lung Cancer 2009, 65(1):80-84.
79. Togashi Y., Masago K., Fukudo M., Tsuchido Y., Okuda C., Kim Y.H., et al. Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Cancer Chemother Pharmacol 2011, 68(4):1089-1092.
80. Grommes C., Oxnard G.R., Kris M.G., Miller V.A., Pao W., Holodny A.I., et al. Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 2011, 13(12):1364-1369.
81. Masuda T., Hattori N., Hamada A., Iwamoto H., Ohshimo S., Kanehara M., et al. Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 2011, 67(6):1465-1469.
82. Katayama T., Shimizu J., Suda K., Onozato R., Fukui T., Ito S., et al. Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib. J Thorac Oncol 2009, 4(11):1415-1419.
83. Fukuhara T., Saijo Y., Sakakibara T., Inoue A., Morikawa N., Kanamori M., et al. Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene. Tohoku J Exp Med 2008, 214(4):359-363.
84. Togashi Y., Masago K., Fukudo M., Terada T., Fujita S., Irisa K., et al. Cerebrospinal fluid concentration of erlotinib and its active metabolite OSI-420 in patients with central nervous system metastases of non-small cell lung cancer. J Thorac Oncol 2010, 5(7):950-955.
85. Choong N.W., Dietrich S., Seiwert T.Y., Tretiakova M.S., Nallasura V., Davies G.C., et al. Gefitinib response of erlotinib-refractory lung cancer involving meninges - role of EGFR mutation. Nat Clin Pract Oncol 2006, 3(1):50-57. quiz 1 p following 57.
86. Yokouchi H., Yamazaki K., Kinoshita I., Konishi J., Asahina H., Sukoh M., et al. Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer. BMC Cancer 2007, 7:p51.
87. Ma S., Xu Y., Deng Q., Yu X. Treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and Gefitinib in a Chinese population. Lung Cancer 2009, 65(2):198-203.
88. Gow C.H., Chien C.R., Chang Y.L., Chiu Y.H., Kuo S.H., Shih J.Y., et al. Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response. Clin Cancer Res 2008, 14(1):162-168.
89. Lind J.S., Lagerwaard F.J., Smit E.F., Senan S. Phase I study of concurrent whole brain radiotherapy and erlotinib for multiple brain metastases from non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2009, 74(5):1391-1396.
90. Das A.K., Sato M., Story M.D., Peyton M., Graves R., Redpath S., et al. Non-small-cell lung cancers with kinase domain mutations in the epidermal growth factor receptor are sensitive to ionizing radiation. Cancer Res 2006, 66(19):9601-9608.
91. Olmez I., Donahue B.R., Butler J.S., Huang Y., Rubin P., Xu Y. Clinical outcomes in extracranial tumor sites and unusual toxicities with concurrent whole brain radiation (WBRT) and Erlotinib treatment in patients with non-small cell lung cancer (NSCLC) with brain metastasis. Lung Cancer 2010, 70(2):174-179.
92. Porta R., Sánchez-Torres J.M., Paz-Ares L., Massutí B., Reguart N., Mayo C., et al. Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 2011, 37(3):624-631.
93. Wu Y.L., Zhou C., Cheng Y., Lu S., Chen G.Y., Huang C., et al. Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases: a phase II study (CTONG-0803). Ann Oncol 2012, 0:1-7.