title: Review of erlotinib in the treatment of advanced non-small cell lung cancer.
abstract: Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinogenesis. There are several methods of EGFR inhibition including monoclonal antibodies directed against the external region and small molecule inhibitors of TK domain. Erlotinib and gefitinib are orally available small molecule EGFR TK inhibitors, with proven efficacy in NSCLC. The most common side effects are skin toxicity and diarrhea. Erlotinib has been shown to improve survival compared to placebo in second or third-line therapy for NSCLC. However, erlotinib in combination with chemotherapy failed to show a survival advantage in two first-line studies which could be due to the timing of chemotherapy administration. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and never smokers have a better response when treated with erlotinib. This could be related to the presence of EGFR mutations, lack of KRAS mutations, or overexpression of EGFR as measured by fluorescent in-situ hybridization (FISH) analysis. Future studies should concentrate on further development of predictors of clinical benefit with erlotinib, overcoming resistance to erlotinib that develops in initial responders, as well as more effective sequencing of erlotinib with chemotherapy and combinations of the drug with other "targeted" therapeutic agents.
authors.affiliation: Palo Alto VA Heath Care Systems, Palo Alto, CA, USA;
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Ganjoo
authors.forename: Heather
authors.initials: H
authors.lastname: Wakelee
references.citation: N Engl J Med. 2005 Jul 14;353(2):123-32
references.pmid: 16014882
references.citation: Cancer Genet Cytogenet. 2007 Mar;173(2):107-13
references.pmid: 17321325
references.citation: J Thorac Oncol. 2009 Jul;4(7):862-8
references.pmid: 19494788
references.citation: Clin Cancer Res. 2006 Jul 1;12(13):3908-14
references.pmid: 16818686
references.citation: Mol Cancer Ther. 2007 Apr;6(4):1223-9
references.pmid: 17406029
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11
references.pmid: 15329413
references.citation: J Clin Oncol. 2005 Apr 10;23(11):2544-55
references.pmid: 15753462
references.citation: Clin Cancer Res. 2007 Jun 15;13(12):3731-7
references.pmid: 17575239
references.citation: J Clin Oncol. 2008 Feb 20;26(6):863-9
references.pmid: 18281658
references.citation: J Clin Oncol. 2000 Jun;18(12):2354-62
references.pmid: 10856094
references.citation: J Clin Oncol. 2007 Jun 1;25(16):2248-55
references.pmid: 17538169
references.citation: J Clin Oncol. 2009 Feb 1;27(4):591-8
references.pmid: 19075278
references.citation: JAMA. 2003 Oct 22;290(16):2149-58
references.pmid: 14570950
references.citation: N Engl J Med. 2006 Dec 14;355(24):2542-50
references.pmid: 17167137
references.citation: Semin Oncol. 2002 Feb;29(1 Suppl 4):3-14
references.pmid: 11894009
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1201-8
references.pmid: 14993230
references.citation: J Clin Oncol. 2005 Sep 1;23(25):5900-9
references.pmid: 16043828
references.citation: J Am Acad Dermatol. 2006 Feb;54(2):358-60
references.pmid: 16443077
references.citation: Clin Cancer Res. 2006 Jul 15;12(14 Pt 2):4421s-4425s
references.pmid: 16857821
references.citation: Clin Cancer Res. 2006 Jun 15;12(12):3652-6
references.pmid: 16778092
references.citation: J Clin Oncol. 2007 May 20;25(15):1960-6
references.pmid: 17452677
references.citation: Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21-6
references.pmid: 15142631
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1545-52
references.pmid: 17442998
references.citation: Cancer Res. 2007 May 15;67(10):4665-70
references.pmid: 17510392
references.citation: N Engl J Med. 2002 Jan 10;346(2):92-8
references.pmid: 11784875
references.citation: JAMA. 2004 Jul 28;292(4):470-84
references.pmid: 15280345
references.citation: J Clin Oncol. 2003 Jun 15;21(12):2237-46
references.pmid: 12748244
references.citation: Clin Cancer Res. 2006 Mar 1;12(5):1647-53
references.pmid: 16533793
references.citation: J Clin Oncol. 2005 Sep 1;23(25):5892-9
references.pmid: 16043829
references.citation: J Clin Oncol. 2007 Mar 1;25(7):760-6
references.pmid: 17228019
references.citation: J Natl Cancer Inst. 2007 Jun 6;99(11):838-46
references.pmid: 17551144
references.citation: Cancer Res. 2002 May 1;62(9):2554-60
references.pmid: 11980649
references.citation: Cancer. 2006 Sep 1;107(5):1034-41
references.pmid: 16878326
references.citation: J Clin Oncol. 2001 Jul 1;19(13):3267-79
references.pmid: 11432895
references.citation: J Clin Oncol. 2000 May;18(10):2095-103
references.pmid: 10811675
references.citation: Nat Med. 2001 Mar;7(3):285-7
references.pmid: 11231620
references.citation: J Biol Chem. 1984 Jun 25;259(12):7755-60
references.pmid: 6330079
references.citation: Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37
references.pmid: 16257339
references.citation: Oncologist. 2007 Jan;12(1):90-8
references.pmid: 17285735
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: Am J Pathol. 1997 Dec;151(6):1523-30
references.pmid: 9403702
references.citation: Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):42-5
references.pmid: 17254038
references.citation: Ann Oncol. 2007 Apr;18(4):752-60
references.pmid: 17317677
references.citation: Mol Biol Med. 1983 Dec;1(5):511-29
references.pmid: 6094961
references.citation: J Clin Oncol. 2006 Jul 20;24(21):3340-6
references.pmid: 16785471
references.citation: J Clin Oncol. 2005 May 10;23(14):3227-34
references.pmid: 15886310
references.citation: J Clin Oncol. 2004 Aug 15;22(16):3238-47
references.pmid: 15310767
references.citation: Cancer Res. 2007 Jun 15;67(12):5667-72
references.pmid: 17575133
references.citation: N Engl J Med. 2005 Jul 14;353(2):133-44
references.pmid: 16014883
references.citation: Acta Derm Venereol. 2004;84(1):23-6
references.pmid: 15040473
references.citation: Science. 2007 May 18;316(5827):1039-43
references.pmid: 17463250
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: J Clin Oncol. 2004 Mar 1;22(5):777-84
references.pmid: 14990632
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: Clin Cancer Res. 2001 Oct;7(10):2958-70
references.pmid: 11595683
references.citation: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6049-55
references.pmid: 17062680
references.citation: Annu Rev Biochem. 1999;68:965-1014
references.pmid: 10872470
references.citation: Int J Cancer. 1993 Jan 21;53(2):209-14
references.pmid: 8381111
references.citation: J Clin Oncol. 2006 Aug 20;24(24):3831-7
references.pmid: 16921034
references.citation: J Clin Oncol. 2004 May 1;22(9):1589-97
references.pmid: 15117980
references.citation: J Clin Oncol. 2003 Oct 15;21(20):3798-807
references.pmid: 12953099
references.citation: J Clin Oncol. 2009 May 20;27(15):2523-9
references.pmid: 19332730
references.citation: J Natl Cancer Inst. 2005 May 4;97(9):643-55
references.pmid: 15870435