Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy

Biologics: Targets and Therapy

Volumn 3, Issue , 2009, Pages 419-428

  Faller, Bryan A ^a   Burtness, Barbara ^a  

^a FOX CHASE CANCER CENTER   (United States)

Author keywords

Cetuximab; Drug resistance; Epidermal growth factor receptor; Erlotinib; Gemcitabine; Pancreatic cancer

Indexed keywords

EID: 77955715149     PISSN: 11775475     EISSN: 11775491     Source Type: Journal    
DOI: 10.2147/BTT.S3170     Document Type: Review

References (67)

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
2. Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997; 15:2403-2413.
3. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960-1966.
4. Grant S, Fisher PB, Dent P. The role of signal transduction pathways in drug and radiation resistance. Cancer Treat Res. 2002;112: 89-108.
5. Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ, Bos JL. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 1988;16:7773-7782.
6. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549-554.
7. Deramaudt T, Rustgi AK. Mutant KRAS in the initiation of pancreatic cancer. Biochim Biophys Acta. 2005;1756:97-101.
8. Fjallskog ML, Lejonklou MH, Oberg KE, Eriksson BK, Janson ET. Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors. Clin Cancer Res. 2003;9: 1469-1473.
9. Tobita K, Kijima H, Dowaki S, et al. Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis. Int J Mol Med. 2003;11:305-309.
10. Ueda S, Ogata S, Tsuda H, et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas. 2004;29:e1-e8.
11. Bloomston M, Bhardwaj A, Ellison EC, Frankel WL. Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg. 2006;23:74-79.
12. Morgan MA, Parsels LA, Kollar LE, Normolle DP, Maybaum J, Lawrence TS. The combination of epidermal growth factor receptor inhibitors with gemcitabine and radiation in pancreatic cancer. Clin Cancer Res. 2008;14:5142-5149.
13. Bruns CJ, Solorzano CC, Harbison MT, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 2000;60:2926-2935.
14. Ng SS, Tsao MS, Nicklee T, Hedley DW. Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol Cancer Ther. 2002;1:777-783.
15. Friess H, Berberat P, Schilling M, Kunz J, Korc M, Buchler MW. Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors. J Mol Med. 1996;74:35-42.
16. Feng J, Adsay NV, Kruger M, et al. Expression of ERRP in normal and neoplastic pancreata and its relationship to clinicopathologic parameters in pancreatic adenocarcinoma. Pancreas. 2002;25:342-349.
17. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008;358:1160-1174.
18. Li J, Zhao M, He P, Hidalgo M, Baker SD. Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007;13:3731-3737.
19. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of nonsmall-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129-2139.
20. Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008;358:1109-1117.
21. Baselga J, Pfister D, Cooper MR, et al. Phase I studies of antiepidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol. 2000;18:904-914.
22. Oh D, Lee K, Lee K, et al. A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/ recurrent pancreatic cancer. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4638.
23. Miksad RA, Schnipper L, Goldstein M. Does a statistically significant survival benefit of erlotinib plus gemcitabine for advanced pancreatic cancer translate into clinical significance and value? J Clin Oncol. 2007;25:4506-4507; author reply 8.
24. Fountzilas G, Bobos M, Kalogera-Fountzila A, et al. Gemcitabine combined with gefitinib in patients with inoperable or metastatic pancreatic cancer: a phase II Study of the Hellenic Cooperative Oncology Group with biomarker evaluation. Cancer Invest. 2008;26: 784-793.
25. Xiong HQ, Rosenberg A, LoBuglio A, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J Clin Oncol. 2004;22:2610-2316.
26. Philip PA, Benedetti J, Fenoglio-Presier C, et al. Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study. J Clin Oncol. 2007;25:LBA4509.
27. Bleickardt E, Argiris A, Rich R, et al. Phase I dose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. Cancer Biol Ther. 2002;1:646-651.
28. Burtness B, Thomas L, Sipples R, et al. Phase II trial of weekly docetaxel/irinotecan combination in advanced pancreatic cancer. Cancer J. 2007;13:257-262.
29. Burtness BA, Powell ME, Berlin D, et al. Phase II ECOG trial of irinotecan/docetaxel with or without cetuximab in metastatic pancreatic cancer: Updated survival and CA19-9 results. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4642.
30. Van Cutsem E, Vervenne WL, Bennouna J, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol. 2009;27:2231-2237.
31. Kindler HL, Gangadhar T, Karrison T, et al. Final analysis of a randomized phase II study of bevacizumab and gemcitabine plus cetuximab or erlotinib in patients with advanced pancreatic cancer. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4502.
32. Ko AH, Dicke K, Gurtler J, et al. Phase II, randomized, open-label study of cetuximab and bevacizumab alone or in combination with fixed-dose rate gemcitabine as first-line therapy for patient with metastatic adenocarcinoma of the pancreas. In: Gastrointestinal Cancers Symposium; 2009 January 15-17; San Francisco, CA; 2009. Abstract 183.
33. Demols A, Mahin C, Marechal R, et al. Cetuximab plus chemoradiation combined therapy for locally advanced inoperable pancreatic adenocarcinoma: A phase I study. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4629.
34. Munter M, Timke C, Adbollahi A, et al. Final results of a phase II trial [PARC-Study ISRCTN56652283] for patients with primary inoperable locally advanced pancreatic cancer combining intensity modulated radiotherapy (IMRT) with cetuximab and gemcitabine. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4613.
35. Loehrer PJ, Powell ME, Cardenes HR, et al. A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4506.
36. Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Cosaert J. Rash as a marker for the efficacy of gemcitabine plus erlotinib-based therapy in pancreatic cancer: Results from the AViTA study. In: Gastrointestinal Cancer Symposium; 2009 January 15-17; San Franciso, CA; 2009. Abstract 117.
37. Li J, Karlsson MO, Brahmer J, et al. CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst. 2006;98:1714-1723.
38. Rudin CM, Liu W, Desai A, et al. Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity. J Clin Oncol. 2008;26:1119-1127.
39. Li J, Cusatis G, Brahmer J, et al. Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients. Cancer Biol Ther. 2007;6:432-438.
40. Fracasso PM, Burris H 3rd, Arquette MA, et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res. 2007;13:986-993.
41. Tejpar S, Peeters M, Humblet Y, et al. Dose-escalation study using up to twice the standard dose of cetuximab in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST study): Preliminary data. J Clin Oncol. 2006;24:3554.
42. 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;274:13176-13180.
43. Huang CL, Yang CH, Yeh KH, et al. EGFR intron 1 dinucleotide repeat polymorphism is associated with the occurrence of skin rash with gefitinib treatment. Lung Cancer. 2009;64:346-351.
44. Sequist LV, Martins RG, Spigel D, et al. First-line gef itinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol. 2008;26:2442-2449.
45. Immervoll H, Hoem D, Kugarajh K, Steine SJ, Molven A. Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes. Virchows Arch. 2006;448:788-796.
46. Iyer RV, Rossi M, Bharthuar M, et al. Evaluation of phosphatidyl inositol 3-kinase catalytic subunit (PI3KCA) and epidermal growth factor receptor (EGFR) gene mutations in pancreatic adenocarcinoma. In: Gastrointestinal Cancers Symposium January 2009; San Francisco, CA; 2009. Abstract 173.
47. Kwak EL, Jankowski J, Thayer SP, et al. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res. 2006;12:4283-4287.
48. Morinaga S, Sugano N, Wada H, et al. Epidermal growth factor receptor (EGFR) status: Mutation and protein expression, and clinicopathology of pancreatic ductal adenocarcinoma. In: Gastrointestinal Cancers Symposium; 2008 January 25-27; Orlando, FL; 2008. Abstract 185.
49. Camp ER, Summy J, Bauer TW, Liu W, Gallick GE, Ellis LM. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin Cancer Res. 2005;11:397-405.
50. Dempke WC, Heinemann V. Resistance to EGF-R (erbB-1) and VEGF-R modulating agents. Eur J Cancer. 2009. In press.
51. Rexer BN, Engelman JA, Arteaga CL. Overcoming resistance to tyrosine kinase inhibitors: lessons learned from cancer cells treated with EGFR antagonists. Cell Cycle. 2009;8:18-22.
52. Bokemeyer C, Bondarenko I, Hartmann JT, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 4000.
53. Jackman DM, Sequist LV, Cioffredi L, et al. Impact of EGFR and KRAS genotype on outcomes in a clinical trial registry of NSCLC patients initially treated with erlotinib or gefitinib. J Clin Oncol. 2008; 26(May 20 Suppl): Abstract 8035.
54. Van Cutsem E, Lang I, D'haens G, et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. J Clin Oncol. 2008;26(May 20 Suppl): Abstract 2.
55. Guix M, Faber AC, Wang SE, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGFbinding proteins. J Clin Invest. 2008;118:2609-2619.
56. Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene. 2003;22:8983-8998.
57. Marmor MD, Skaria KB, Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys. 2004;58: 903-913.
58. Jhawer M, Goel S, Wilson AJ, et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res. 2008;68:1953-1961.
59. Bianco R, Shin I, Ritter CA, et al. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene. 2003;22:2812-2822.
60. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039-1043.
61. Ihle NT, Paine-Murrieta G, Berggren MI, et al. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther. 2005;4:1349-1357.
62. Abraham RT, Gibbons JJ. The mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy. Clin Cancer Res. 2007;13:3109-3114.
63. Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer. 2004;4:335-348.
64. Bianco R, Garofalo S, Rosa R, et al. Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs. Br J Cancer. 2008;98: 923-930.
65. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005;352:786-792.
66. Kosaka T, Yatabe Y, Endoh H, et al. Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res. 2006;12: 5764-5769.
67. Bean J, Brennan C, Shih JY, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A. 2007;104:20932-20937.