title: Erlotinib in the treatment of advanced pancreatic cancer.
abstract: Single agent gemcitabine has been the mainstay of therapy for advanced pancreatic cancer over the past decade. Multiple trials of newer chemotherapeutic agents both alone and in combination have yielded disappointing results, spurring the ongoing search for new agents and combinations in this aggressive malignancy. Inhibitors of the epidermal growth factor receptor (EGFR) have shown promising activity in multiple solid tumors types, and preclinical data support a role for EGFR inhibition in pancreatic cancer. A recent phase III study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) demonstrated a significant survival benefit with the addition of the EGFR tyrosine kinase inhibitor, erlotinib, to gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer, becoming the first phase III study to demonstrate a survival benefit of combination therapy as well as targeted therapy in this disease. This article reviews the evidence supporting EGFR inhibition and the use of erlotinib in advanced pancreatic cancer as well as future implications of targeted therapy in this challenging malignancy.
authors.affiliation: University of California, San Francisco, Comprehensive Cancer Center.
authors.forename: Robin K
authors.initials: RK
authors.lastname: Kelley
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ko
references.citation: Cancer Res. 1999 Apr 15;59(8):1935-40
references.pmid: 10213503
references.citation: Pancreas. 2004 Jul;29(1):e1-8
references.pmid: 15211117
references.citation: J Clin Oncol. 2005 Aug 1;23(22):5235-46
references.pmid: 16051966
references.citation: J Clin Oncol. 2009 Nov 20;27(33):5513-8
references.pmid: 19858379
references.citation: Cancer Res. 2000 Jun 1;60(11):2926-35
references.pmid: 10850439
references.citation: Mol Biol Cell. 1999 Aug;10(8):2493-506
references.pmid: 10436007
references.citation: J Clin Oncol. 1997 Jun;15(6):2403-13
references.pmid: 9196156
references.citation: J Clin Oncol. 2005 Mar 20;23(9):1803-10
references.pmid: 15677699
references.citation: JAMA. 2007 Jan 17;297(3):267-77
references.pmid: 17227978
references.citation: J Natl Cancer Inst. 2005 May 4;97(9):643-55
references.pmid: 15870435
references.citation: J Clin Oncol. 2006 Sep 20;24(27):4441-7
references.pmid: 16983112
references.citation: Pharmacol Ther. 2004 Apr;102(1):37-46
references.pmid: 15056497
references.citation: Dig Surg. 2006;23(1-2):74-9
references.pmid: 16717472
references.citation: J Clin Oncol. 2004 Sep 15;22(18):3776-83
references.pmid: 15365074
references.citation: Ann Oncol. 2008 Jan;19(1):86-91
references.pmid: 17878176
references.citation: Int J Cancer. 2007 Feb 1;120(3):514-23
references.pmid: 17096356
references.citation: Anticancer Res. 1993 May-Jun;13(3):565-9
references.pmid: 8317885
references.citation: Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4283-7
references.pmid: 16857803
references.citation: Crit Rev Oncol Hematol. 2008 May;66(2):155-62
references.pmid: 18083041
references.citation: Br J Cancer. 2001 Apr 6;84(7):926-35
references.pmid: 11286473
references.citation: Cancer. 2006 Sep 15;107(6):1207-18
references.pmid: 16909423
references.citation: J Clin Oncol. 2001 Sep 15;19(18 Suppl):32S-40S
references.pmid: 11560969
references.citation: Ann Oncol. 2005 Sep;16(9):1425-33
references.pmid: 16012181
references.citation: J Clin Oncol. 2002 Aug 1;20(15):3270-5
references.pmid: 12149301
references.citation: Int J Oncol. 2004 Jul;25(1):203-10
references.pmid: 15202007
references.citation: J Clin Oncol. 2005 Sep 1;23(25):5900-9
references.pmid: 16043828
references.citation: Surgery. 2007 Apr;141(4):464-9
references.pmid: 17383523
references.citation: Cancer. 2007 Apr 15;109(8):1561-9
references.pmid: 17354229
references.citation: J Clin Oncol. 2003 Jul 15;21(14):2787-99
references.pmid: 12860957
references.citation: Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37
references.pmid: 11252954
references.citation: Cochrane Database Syst Rev. 2006 Jul 19;(3):CD002093
references.pmid: 16855985
references.citation: J Clin Oncol. 2007 May 20;25(15):1960-6
references.pmid: 17452677
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1545-52
references.pmid: 17442998
references.citation: J Pharmacol Exp Ther. 1999 Nov;291(2):739-48
references.pmid: 10525095
references.citation: J Clin Oncol. 2006 Mar 1;24(7):1219-20; author reply 1220-1
references.pmid: 16505443
references.citation: JOP. 2007 Jan 09;8(1):4-15
references.pmid: 17228128
references.citation: J Surg Res. 2006 Sep;135(1):195-201
references.pmid: 16678855
references.citation: Cancer Res. 1997 Nov 1;57(21):4838-48
references.pmid: 9354447
references.citation: Ann Surg Oncol. 2007 Jul;14(7):2150-8
references.pmid: 17453292
references.citation: J Clin Oncol. 2005 Oct 1;23(28):6829-37
references.pmid: 15998907
references.citation: Clin Cancer Res. 2001 Mar;7(3):682-90
references.pmid: 11297265
references.citation: Int J Mol Med. 2003 Mar;11(3):305-9
references.pmid: 12579331
references.citation: J Clin Oncol. 2004 Jan 1;22(1):77-85
references.pmid: 14701768
references.citation: J Clin Oncol. 2005 Nov 1;23(31):8081-92
references.pmid: 16204011
references.citation: Cancer Chemother Pharmacol. 2007 Jul;60(2):295-303
references.pmid: 17149608
references.citation: J Clin Oncol. 2007 Jun 1;25(16):2212-7
references.pmid: 17538165
references.citation: Mol Cancer Ther. 2002 Aug;1(10):777-83
references.pmid: 12492110
references.citation: Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1192-9
references.pmid: 16626884
references.citation: J Clin Oncol. 2006 Oct 20;24(30):4914-21
references.pmid: 17050875
references.citation: J Clin Oncol. 2001 Jul 1;19(13):3267-79
references.pmid: 11432895
references.citation: Oncogene. 1997 Sep 4;15(10):1191-7
references.pmid: 9294612
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: J Clin Oncol. 2023 Oct 20;41(30):4714-4720
references.pmid: 37847995
references.citation: Ann Oncol. 2007 Oct;18(10):1652-9
references.pmid: 17660491
references.citation: Ann Oncol. 2007 Apr;18(4):752-60
references.pmid: 17317677
references.citation: Clin Cancer Res. 2007 Jul 1;13(13):3913-21
references.pmid: 17606725
references.citation: J Clin Oncol. 2007 Jun 1;25(16):2248-55
references.pmid: 17538169
references.citation: J Clin Oncol. 2005 May 20;23(15):3509-16
references.pmid: 15908661
references.citation: J Clin Oncol. 2005 Oct 1;23(28):6838-45
references.pmid: 15998906
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: J Natl Cancer Inst. 2003 Jun 18;95(12):851-67
references.pmid: 12813169
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035
references.citation: J Clin Oncol. 2005 Apr 10;23(11):2556-68
references.pmid: 15767641