Overview of gefitinib in non-small cell lung cancer: An Asian perspective

Japanese Journal of Clinical Oncology

Volumn 39, Issue 3, 2009, Pages 137-150

  Jiang, Haiyi ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Asian patients; EGFR mutations; Gefitinib; Non small cell lung cancer

Indexed keywords

CARBOPLATIN; CISPLATIN; CYTOTOXIC AGENT; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; GEMCITABINE; IRINOTECAN; K RAS PROTEIN; NAVELBINE; PACLITAXEL; PLACEBO;

ACNE; ADVANCED CANCER; ALOPECIA; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; ASIAN; ASTHENIA; BONE MARROW DEPRESSION; CANCER INCIDENCE; CANCER INHIBITION; CANCER PAIN; CHEMOTHERAPY INDUCED EMESIS; CHINA; CLINICAL TRIAL; CONSTIPATION; COUGHING; DIARRHEA; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; DYSPNEA; FEBRILE NEUTROPENIA; FEVER; FLUID RETENTION; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC TRANSFECTION; HEMOPTYSIS; HUMAN; INTERSTITIAL LUNG DISEASE; JAPAN; KOREA; LOW DRUG DOSE; LOWER RESPIRATORY TRACT INFECTION; LUNG INFECTION; LUNG NON SMALL CELL CANCER; MEDLINE; MULTIPLE CYCLE TREATMENT; MUTATIONAL ANALYSIS; MYALGIA; NAUSEA; NEPHROTOXICITY; NEUROTOXICITY; NEUTROPENIA; OVERALL SURVIVAL; PARONYCHIA; PERIPHERAL EDEMA; PHENOTYPE; PNEUMONIA; PROTEIN SYNTHESIS INHIBITION; PRURITUS; REFERENCE DATABASE; REVIEW; SIDE EFFECT; SOMATIC MUTATION; STOMATITIS; TAIWAN; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; ASIAN CONTINENTAL ANCESTRY GROUP; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; FAR EAST; HUMANS; LUNG NEOPLASMS; MUTATION; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; TREATMENT OUTCOME;

EID: 61449172019     PISSN: 03682811     EISSN: 14653621     Source Type: Journal    
DOI: 10.1093/jjco/hyn139     Document Type: Review

References (99)

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.
2. Detterbeck FC, Rivera MP, Socinski MA. Diagnosis and treatment of lung cancer: An evidence-based guide for the practicing physician. Philadelphia, WB Saunders 2000, (eds.).
3. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183-232.
4. Rusch V, Baselga J, Cordon-Cardo C, Orazem J, Zaman M, Hoda S, et al. Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. Cancer Res 1993;53:2379-85.
5. Fujino S, Enokibori T, Tezuka N. A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur J Cancer 1996;32A:2070-4.
6. Pavelic K, Banjac Z, Pavelic J, Spaventi S. Evidence for a role of EGF receptor in the progression of human lung carcinoma. Anticancer Res 1993;13:1133-8.
7. Volm M, Rittgen W, Drings P. Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. Br J Cancer 1998;77:663-9.
8. Jeon YK, Sung SW, Chung JH, Park WS, Seo JW, Kim CW, et al. Clinicopathologic features and prognostic implications of epidermal growth factor receptor (EGFR) gene copy number and protein expression in non-small cell lung cancer. Lung Cancer 2006;54: 387-98.
9. Adiseshaiah P, Vaz M, Machireddy N, Kalvakolanu DV, Reddy SP. A Fra-1-dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion. J Cell Physiol 2008;216:405-12.
10. Yatabe Y, Takahashi T, Mitsudomi T. Epidermal growth factor receptor gene amplification is acquired in association with tumor progression of EGFR-mutated lung cancer. Cancer Res 2008;68:2106-11.
11. Okuda K, Sasaki H, Kawano O, Yukiue H, Yokoyama T, Yano M, et al. Epidermal growth factor receptor gene mutation, amplification and protein expression in malignant pleural mesothelioma. J Cancer Res Clin Oncol 2008;134:1105-11.
12. Tsakiridis T, Cutz JC, Singh G, Hirte H, Okawara G, Corbett T, et al. Association of phosphorylated epidermal growth factor receptor with survival in patients with locally advanced non-small cell lung cancer treated with radiotherapy. J Thorac Oncol 2008;3:716-22.
13. Negoro S, Nakagawa K, Fukuoka M, Kudoh S, Tamura T, Yoshimura N, et al. Final results of a phase I intermittent dose-escalation trial of ZD1839 ('Iressa') in Japanese patients with various solid tumours. Proc Am Soc Clin Oncol 2001;20:324 (Abstract 1292).
14. Ranson M, Hammond LA, Ferry D, Kris M, Tullo A, Murray PI, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: Results of a phase I trial. J Clin Oncol 2002;20:2240-50.
15. Park K, Goto K. A review of the benefit-risk profile of gefitinib in Asian patients with advanced non-small-cell lung cancer. Curr Med Res Opin 2006;22:561-73.
16. Armour A. Gefitinib in advanced non-small cell lung cancer: Clinical experience in patients of Asian origin. Asia Pac J Clin Oncol 2007;3:66-78.
17. Chen YM, Perng RP, Tsai CM. Gefitinib treatment is highly effective in non-small-cell lung cancer patients failing previous chemotherapy in Taiwan: A prospective phase II study. J Chemother 2005;17:679-84.
18. Cufer T, Vrdoljak E, Gaafar R, Erensoy I, Pemberton K. Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer. Anticancer Drugs 2006;17:401-9.
19. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J-Y, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003;21:2237-46.
20. Guan ZZ, Zhang L, Li L-Y, Jiang G-L, Liu X, Chu D, et al. Efficacy of gefitinib on Chinese patients with locally advanced or metastatic non-small-cell lung cancer: A clinical trial. Ai Zheng 2005;24:980-4.
21. Kim ES, Hirsch V, Mok T, Socinski M, Gervais R, Wu YL, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer: A randomised phase III trial (INTEREST). Lancet 2008;372:1809-18.
22. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer. A randomized trial. J Am Med Assoc 2003;290:2149-58.
23. Lee D, Kim S, Park K, Kim J, Lee J, Shin S, et al. A randomized open-label study of gefitinib versus docetaxel in patients with advanced/ metastatic non-small cell lung cancer (NSCLC) who have previously received platinum-based chemotherapy. J Clin Oncol 2008;26(Suppl.) (Abstract 8025).
24. Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, et al. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol 2008;26:4244-52.
25. Thatcher N, Chang A, Parikh P, Rodrigues PJ, 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;366:1527-37.
26. Nishiwaki Y, Yano S, Tamura T, Nakagawa K, Kudoh S, Horai T, et al. Subset analysis of data in the Japanese patients with NSCLC from IDEAL 1 study on ge.tinib. Gan To Kagaku Ryoho 2004;31:567-73.
27. Chang A, Parikh P, Thongprasert S, Tan E-H, Perng R-P, Ganzon D, et al. Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: Subset analysis from the ISEL study. J Thorac Oncol 2006;1:847-55.
28. 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;47:129-38.
29. Wang MZ, Li LY, Wang SL, Zhang XT, Zhong W, Zhang L. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer. Chin Med J (Engl) 2006;119: 63-8.
30. Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: Results of a phase I trial. J Clin Oncol 2002;20:3815-25.
31. Hirsch FR, Varella-Garcia M, Bunn PA Jr, Franklin WA, 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;24:5034-42.
32. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT 1. J Clin Oncol 2004;22:777-84.
33. Hashizume T, Ogura T, Kozawa S, Kobayashi N, Tagawa A, Miyazawa N, et al. Gefitinib as a first-line therapy in patients with advanced non-small cell lung cancer. Gan To Kagaku Ryoho 2006;33:467-70.
34. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial - INTACT 2. J Clin Oncol 2004;22:785-94.
35. Hida T, Okamoto I, Kashii T, Satouchi M, Ichinose Y, Katakami N, et al. Randomised phase III study of platinum-doublet chemotherapy followed by gefitinib versus continued platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): Results of West Japan Thoracic Oncology Group trial (WJTOG). J Clin Oncol 2008;26 (Abstract LBA8012).
36. Lee DH, Han JY, Yu SY, Kim HY, Nam BH, Hong EK, et al. The role of gefitinib treatment for Korean never-smokers with advanced or metastatic adenocarcinoma of the lung: A prospective study. J Thorac Oncol 2006;1:965-71.
37. Lin W-C, Chiu C-H, Liou J-L, Chen Y-M, Perng R-P, Tsai C-M. Gefitinib as front-line treatment in Chinese patients with advanced non-small-cell lung cancer. Lung Cancer 2006;54:193-9.
38. Mok T, Wu YL, Thongprasert S, Yang C-H, Chu D, Saijo N, et al. Phase III, randomised, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer. Ann Oncol 2008;19(Suppl. 8) (viii1, Abstract LBA2).
39. Niho S, Kubota K, Goto K, Yoh K, Ohmatsu H, Kakinuma R, et al. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer: A phase II study. J Clin Oncol 2006;24: 64-9.
40. Reck M, Buchholz E, Romer KS, Krutzfeldt K, Gatzemeier U, Manegold C. Gefitinib monotherapy in chemotherapy-naive patients with inoperable stage III/IV non-small-cell lung cancer. Clin Lung Cancer 2006;7:406-11.
41. Suzuki R, Hasegawa Y, Baba K, Saka H, Saito H, Taniguchi H, et al. A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer. Br J Cancer 2006;94: 1599-603.
42. Yang CH, Yu CJ, Shih JY, Chang YC, Hu FC, Tsai MC, 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;26:2745-53.
43. Kimura H, Kasahara K, Kawaishi M, Kunitoh H, Tamura T, Holloway B, et al. Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res 2006;12:3915-21.
44. Spigel DR, Hainsworth JD, Burkett ER, Burris HA, Yardley DA, Thomas M, et al. Single-agent gefitinib in patients with untreated advanced non-small-cell lung cancer and poor performance status: A Minnie Pearl Cancer Research Network Phase II Trial. Clin Lung Cancer 2005;7:127-32.
45. Agiris A, Mittal N. Gefitinib as first-line, compassionate use therapy in patients with advanced non-small-cell lung cancer. Lung Cancer 2004;43:317-22.
46. D'Addario G, Rauch D, Stupp R, Pless M, Stahel R, Mach N, et al. Multicentre phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03. Ann Oncol 2008;19:739-45.
47. Asahina H, Yamazaki K, Kinoshita I, Sukoh N, Harada M, Yokouchi H, et al. A phase II trial of gefitinib as first-line therapy for advanced non-small-cell lung cancer with epidermal growth factor receptor mutations. Br J Cancer 2006;95:998-1004.
48. Inoue A, Suzuki T, Fukuhara T, Maemondo M, Kimura Y, Morikawa N, et al. Prospective Phase II Study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 2006;24:3340-6.
49. Tamura K, Okamoto I, Kashii T, Negoro S, Hirashima T, Kudoh S, et al. Multicentre prospective phase II trial of gefitinib for advanced non-small-cell lung cancer with epidermal growth factor receptor mutations: Results of the West Japan Thoracic Oncology Group trial (WJTOG0403). Br J Cancer 2008;98:907-14.
50. Sequist LV, Martins R, Spigel DR, Grunberg SM, Spira A, Janne P, et al. First-line gefitinib in patients with advanced non-small cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 2008;26:2442-9.
51. Morita S, Hirashima T, Hagiwara K, Hida T, Sunaga N, Sugio K, et al. I-CAMP Study Group. Gefitinib combined survival analysis of the mutation positives from the prospective phase II trials (I-CAMP). J Clin Oncol 2008;26(Suppl.) (Abstract 8101).
52. Forsythe B, Faulkner K. Overview of the tolerability of gefitinib (IRESSA™) monotherapy. Clinical experience in non-small-cell lung cancer. Drug Saf 2004;27:1081-92.
53. Fukuoka M, Kris M, Giaccone G, Lynch T, Nakagawa K, Kelly K, et al. Phase II trials of gefitinib ('Iressa', ZD1839): Rapid and durable objective responses in patients with advanced non-small-cell lung cancer (IDEAL 1 and IDEAL 2). Lung Cancer 2003;41(Suppl. 2):S247-S248 (Abstract P-615).
54. Kudoh S, Kato H, Nishiwaki Y, Fukuoka M, Nakata K, Ichinose Y, et al. Interstitial lung disease in Japanese patients with lung cancer: A cohort and nested case-control study. Am J Respir Crit Care Med 2008;177:1348-57.
55. Takamochi K, Suzuki K, Bashar AH, Yajima K, Mochizuki T, Itaya T, et al. Readministration of gefitinib in a responder after treatment discontinuation due to gefitinib-related interstitial lung disease: A case report. J Med Case Reports 2008;17:138.
56. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2006;24:2549-56.
57. Tsuboi M, Le Chevalier T. Interstitial lung disease in patients with non-small-cell lung cancer treated with epidermal growth factor receptor inhibitors. Med Oncol 2006;23:161-70.
58. Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, et al. Severe acute interstitial pneumonia and gefitinib. Lancet 2003;361:137-9.
59. Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, et al. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: Results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 2006;24:3657-63.
60. Yoshida S. The results of gefitinib prospective investigation. Med Drug J 2005;41:772-89.
61. Nakagawa K, Tamura T, Negoro S, Kudoh S, Yamamoto N, Yamamoto N, et al. Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid malignant tumours. Ann Oncol 2003;14:922-30.
62. Baselga J, Rischin D, Ranson M, Calvert H, Raymond E, Kieback DG, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 2002;20:4292-302.
63. Swaisland H, Laight A, Stafford L, Jones H, Morris C, Dane A, et al. Pharmacokinetics and tolerability of the orally active selective epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in healthy volunteers. Clin Pharmacokinet 2001;40:297-306.
64. Swaisland HC, Smith RP, Laight A, Kerr DJ, Ranson M, Wilder-Smith CH, et al. Single-dose clinical pharmacokinetic studies of gefitinib. Clin Pharmakokinetic 2005;44: 1165-77.
65. Haura E, Sommers E, Becker D, McKillop D, Bepler G. Pilot phase II study of preoperative gefitinib in early stage non-small cell lung cancer with assessment of intratumour gefitinib levels and tumour target modulation. J Clin Oncol 2007;25 (Abstract 7603).
66. Guo J, Zhou C, Deng Q, Ren S, Zhang J. Effect of EGFR mutations on gefitinib in advanced previous treated non-small-cell lung cancer. J Clin Oncol 2008;26(Suppl.) (Abstract 19132).
67. Sunaga N, Tomizawa Y, Yanagitani N, Iijima H, Kaira K, Shimizu K, et al. Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small-cell lung cancer with EGFR mutations, irrespective of previous chemotherapy. Lung Cancer 2007;56:383.
68. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004;101:13306-11.
69. Darwish S, Ludovini V, Pistola L, Bianconi F, Betti M, Chiari R, et al. EGFR, KRAS, PIK3CA mutations and response to tyrosine kinase inhibitors (TKIs) in advanced NSCLC patients. J Clin Oncol 2008;26(Suppl.) (Abstract 22003).
70. Sasaki H, Endo K, Takada M, Kawahara M, Tanaka H, Kitahara N, et al. EGFR Polymorphism of the Kinase Domain in Japanese Lung Cancer. J Surg Res 2007;148:260-3.
71. Nomura M, Shigematsu H, Li L, Suzuki M, Takahashi T, Estess P, et al. Polymorphisms, mutations, and ampli.cation of the EGFR gene in non-small cell lung cancers. PLoS Med 2007;4:e125.
72. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, 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: 2129-39.
73. Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res 2004;10:8195-203.
74. Sutani A, Nagai Y, Udagawa K, Uchida Y, Murayama Y, Tanaka T, et al. Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp. Abstract presented at the ASCOAtlantaGA2-6June2006.
75. Douillard JY, Hirsch V, Mok T, Socinski MA, Watkins C, Lowe E, et al. Molecular and clinical subgroup analyses from a phase III trial comparing gefitinib with docetaxel in previously treated non-small cell lung cancer (INTEREST). J Clin Oncol 2008;26(Suppl.): Abs 8001.
76. Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005;97:339-46.
77. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500.
78. Wu JY, Yu CJ, Yang CH, Wu SG, Chiu YH, Gow CH, et al. First or Second-Line Therapy With Gefitinib Produces Equal Survival in Non Small Cell Lung Cancer. Am J Respir Crit Care Med 2008
79. Yang CH. EGFR tyrosine kinase inhibitors for the treatment of NSCLC in East Asia: Present and future. Lung Cancer 2008;60(Suppl. 2):S23-S30.
80. Sasaki H, Okuda K, Takada M, Kawahara M, Kitahara N, Matsumura A, et al. A novel EGFR mutation D1012H and polymorphism at exon 25 in Japanese lung cancer. Cancer Res Clin Oncol 2008;134:1371-6.
81. Bell DW, Brannigan BW, Matsuo K, Finkelstein DM, Sordella R, Settleman J, et al. Increased Prevalence of EGFR-Mutant Lung Cancer in Women and in East Asian Populations: Analysis of Estrogen-Related Polymorphisms. Clin Cancer Res 2008;14:4079-84.
82. Kharrat N, Al'Fadhli S, Rebai M, Aifa MS, Kallel I, Khabir A, et al. (AC) dinucleotide repeat polymorphism in intron 1 of human EGFR shows ethnic speci.cities and high evidence for association with breast cancer. Int J Biol Markers 2007;22:258-64.
83. Calvo E, Baselga J. Ethnic differences in response to epidermal growth factor receptor tyrosine kinase inhibitors. J Clin Oncol 2006;24:2158-63.
84. Liu W, Innocenti F, Chen P, Das S, Cook EH, Jr, Ratain MJ. Interethnic difference in the allelic distribution of human epidermal growth factor receptor intron 1 polymorphism. Clin Cancer Res 2003;9:1009-12.
85. Gebhardt F, Zanker KS, Brandt B. Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J Biol Chem 1999;274:13176-80.
86. Rosell R, Ichinose Y, Taron M, Sarries C, Queralt C, Mendez P, et al. Mutations in the tyrosine kinase domain of the EGFR gene associated with gefitinib response in non-small-cell lung cancer. Lung Cancer 2005;50:25-33.
87. Greulich H, Chen TH, Feng W, Janne P, Alvarez J, Zappaterra M, et al. Oncogenic transformation by inhibitor-sensitive and resistant EGFR mutants. PLoS Med 2005;2:1167-76.
88. Okano T, Kondo T, Fujii K, Nishimura T, Takano T, Ohe Y, et al. Proteomic signature corresponding to the response to gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma. Clin Cancer Res 2007;13:799-805.
89. Zucali PA, Ruiz MG, Giovannetti E, Destro A, Varella-Garcia M, Floor K, et al. Role of cMET expression in non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors. Ann Oncol 2008;19:1605-12.
90. Nishimura Y, Yoshioka K, Bereczky B, Itoh K. Evidence for efficient phosphorylation of EGFR and rapid endocytosis of phosphorylated EGFR via the early/late endocytic pathway in a gefitinib-sensitive non-small cell lung cancer cell line. Mol Cancer 2008;7:42.
91. Janne PA. Challenges of detecting EGFR T790M in gefitinib/ erlotinib-resistant tumours. Lung Cancer 2008;60(Suppl. 2):S3-S9.
92. Wang Z, Wu YL, Zhang GC, Zhou Q, Xu CR, Guo AL. EGFR/KRAS mutations and gefitinib therapy in Chinese NSCLC patients. Onkologie 2008;31:174-8.
93. Ho C, Murray N, Laskin J, Melosky B, Anderson H, Bebb G. Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America. Lung Cancer 2005;49:225-31.
94. Kondo M, Yokoyama T, Fukui T, Yoshioka H, Yokoi K, Nagasaka T, et al. Mutations of epidermal growth factor receptor of non-small cell lung cancer were associated with sensitivity to gefitinib in recurrence after surgery. Lung Cancer 2005;50:385-91.
95. 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;23:2513-20.
96. Tokumo M, Toyooka S, Kiura K, Shigematsu H, Tomii K, Aoe M, et al. The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res 2005;11:1167-73.
97. Hotta K, Kiura K, Toyooka S, Takigawa N, Soh J, Fujiwara Y, et al. Clinical signi.cance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small-cell lung cancer. J Thorac Oncol 2007;2:632-7.
98. Okami J, Taniguchi K, Higashiyama M, Maeda J, Oda K, Orita N, et al. Prognostic factors for gefitinib-treated postoperative recurrence in non-small cell lung cancer. Oncology 2007;72:234-42.
99. Takano T, Fukui T, Ohe Y, Tsuta K, Yamamoto S, Nokihara H, et al. EGFR mutations predict survival benefit from gefitinib in patients with advanced lung adenocarcinoma: A historical comparison of patients treated before and after gefitinib approval in Japan. J Clin Oncol 2008;26:5589-95.