Genomics and pharmacogenomics of pancreatic adenocarcinoma

Pharmacogenomics Journal

Volumn 12, Issue 1, 2012, Pages 1-9

  Lowery, M A ^a   O'Reilly, E M ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

genetics; molecular markers; pancreatic cancer; targeted therapy

Indexed keywords

CALCIUM BINDING PROTEIN; CAPECITABINE; CETUXIMAB; CYTIDINE DERIVATIVE; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; FLUOROURACIL; GEMCITABINE; GEMCITABINE 5' ELAIDATE; IRINOTECAN; K RAS PROTEIN; NANOPARTICLE; OSTEONECTIN; OXALIPLATIN; PACLITAXEL; PROTEIN S100A2; UNCLASSIFIED DRUG; VISMODEGIB;

ADJUVANT THERAPY; BLOOD TOXICITY; CANCER MORTALITY; CANCER SURVIVAL; DIARRHEA; DRUG METABOLISM; DRUG RESPONSE; GASTROINTESTINAL TOXICITY; GENETIC POLYMORPHISM; GENETIC RISK; GENOMICS; HUMAN; MOLECULARLY TARGETED THERAPY; NEUTROPENIA; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREAS SURGERY; PHARMACOGENOMICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SOMATIC MUTATION;

ADENOCARCINOMA; ANIMALS; ANTINEOPLASTIC AGENTS; GENOMICS; GERM-LINE MUTATION; HUMANS; PANCREATIC NEOPLASMS; PHARMACOGENETICS;

EID: 84856224253     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/tpj.2011.52     Document Type: Review

References (82)

1. Burris III H, Moore M, Andersen J, Green M, Rothenberg M, Modiano M 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. (Pubitemid 27251144)
2. Moore M, Goldstein D, Hamm J, Figer A, Hecht J, Gallinger S 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. (Pubitemid 46972777)
3. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y et al. FOLFIRINOX versus Gemcitabine for metastatic pancreatic cancer. N Eng J Med 2011; 364: 1817-1825.
4. Colucci G, Giuliani F, Gebbia V, Biglietto M, Rabitti P, Uomo G et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer 2002; 94: 902-910. (Pubitemid 34150843)
5. Cunningham D, Chau I, Stocken D, Valle J, Smith D, Steward W et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009; 27: 5513-5518.
6. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C. Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 2008; 8: 82. (e-pub 1 April 2008).
7. Sultana A, Smith CT, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 2007; 25: 2607-2615. (Pubitemid 47041235)
8. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61: 212-236. (e-pub 21 June 2011).
9. Koorstra J-B, Feldmann G, Habbe N, Maitra A. Morphogenesis of pancreatic cancer: role of pancreatic intraepithelial neoplasia (PanINs). Langenbeck Arch Surg 2008; 393: 561-570.
10. Ghaneh P, Costello E, Neoptolemos J. Biology and management of pancreatic cancer. Gut 2007; 56: 1134-1152. (Pubitemid 47123247)
11. Lüttges J, Reinecke-Lüthge A, Möllmann B, Menke MAOH, Clemens A, Klimpfinger M et al. Duct changes and K-ras mutations in the diseasefree pancreas: analysis of type, age relation and spatial distribution. Virchows Arch 1999; 435: 461-468.
12. Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clinic Cancer Res 2000; 6: 2969-2972. (Pubitemid 30637716)
13. Jones S, Zhang X, Parsons DW, Lin J, Leary R, Angenendt P et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-1806.
14. Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 2010; 467: 1114-1117.
15. Campbell PJ, Yachida S, Mudie LJ, Stephens PJ, Pleasance ED, Stebbings LA et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 2010; 467: 1109-1113. (e-pub 29 October 2010).
16. Iacobuzio Donahue C, Fu B, Yachida S, Luo M, Abe H, Henderson C et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009; 27: 1806-1813.
17. Crane CH, Varadhachary GR, Yordy JS, Staerkel GA, Javle MM, Safran H et al. Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. J Clin Oncol 2011 (e-pub 29 June 2011).
18. Ghadirian P. Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol 1991; 10: 183-196.
19. Lynch HT. Genetics and pancreatic cancer. Arch Surg 1994; 129: 266-268. (Pubitemid 24103317)
20. Klein AP, Brune KA, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJA et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res 2004; 64: 2634-2638. (Pubitemid 38523922)
21. Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen MG, Booker SV et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000; 119: 1447-1453. (Pubitemid 32198669)
22. Lowenfels A, Maisonneuve P, DiMagno E, Elitsur Y, Gates Jr L, Perrault J et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997; 89: 442-446. (Pubitemid 27136736)
23. Lowenfels AB, Maisonneuve P, Whitcomb DC, Lerch MM, DiMagno EP. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 2001; 286: 169-170. (Pubitemid 32640846)
24. Lynch HT, Voorhees GJ, Lanspa SJ, McGreevy PS, Lynch JF. Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. Br J Cancer 1985; 52: 271-273. (Pubitemid 15229364)
25. Lynch H, Fusaro R, Lynch J, Brand R. Pancreatic cancer and the FAMMM syndrome. Familial Cancer 2008; 7: 103-112.
26. Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 1993; 34: 1394-1396. (Pubitemid 23293626)
27. Friedenson B. BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed 2005; 7: 60. (e-pub 22 December 2005).
28. Lynch HT, Deters CA, Snyder CL, Lynch JF, Villeneuve P, Silberstein J et al. BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet 2005; 158: 119-125. (Pubitemid 40417693)
29. Hahn SA, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B et al. BRCA2 germline mutations in familial pancreatic carcinoma. JNCI 2003; 95: 214-221. (Pubitemid 36240634)
30. van der Heijden M, Brody J, Dezentje D, Gallmeier E, Cunningham S, Swartz M et al. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res 2005; 11: 7508-7515. (Pubitemid 41507712)
31. McCabe N, Lord C, Tutt ANJ, Martin NMB, Smith GCM, Ashworth A. BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of poly (ADP-ribose) polymerase: an issue of potency. Cancer Biol Ther 2005; 4: 934-936. (Pubitemid 41598586)
32. Sandhu SK, Yap TA, de Bono JS. Poly(ADP-ribose) polymerase inhibitors in cancer treatment: A clinical perspective. Eur J Cancer 2010; 46: 9-20.
33. Kyle S, Thomas HD, Mitchell J, Curtin NJ. Exploiting the Achilles heel of cancer: the therapeutic potential of poly(ADP-ribose) polymerase inhibitors in BRCA2-defective cancer. Br J Radiol 2008; 81: S6-11.
34. Tutt A, Robson M, Garber JE, Domchek S, Audeh MW, Weitzel JN et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. J Clin Oncol 2009; 27: CRA501-CRA50.
35. Audeh MW, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C et al. Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer. J Clin Oncol 2009; 27: 5500-550.
36. Fogelman DR, Wolff RA, Kopetz S, Javle M, Bradley C, Mok I et al. Evidence for the efficacy of iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer. Anticancer Res 2011; 31: 1417-1420.
37. Lowery MA, Kelsen DP, Stadler ZK, Yu KH, Janjigian YY, Ludwig E et al. An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist 2011 (e-pub 22 September 2011).
38. Javle MM, Gibbs JF, Iwata KK, Pak Y, Rutledge P, Yu J et al. Epithelialmesenchymal transition (EMT) and activated extracellular signalregulated kinase (p-Erk) in surgically resected pancreatic cancer. Ann Surg Oncol 2007; 14: 3527-3533. (e-pub 20 September 2007). (Pubitemid 350160113)
39. Masugi Y, Yamazaki K, Hibi T, Aiura K, Kitagawa Y, Sakamoto M. Solitary cell infiltration is a novel indicator of poor prognosis and epithelialmesenchymal transition in pancreatic cancer. Hum Pathol 2010; 41: 1061-1068. (e-pub 24 April 2010).
40. Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol 2007; 14: 3629-3637. (e-pub 3 October 2007). (Pubitemid 350160137)
41. Pan J-J, Yang M-H. The role of epithelial-mesenchymal transition in pancreatic cancer. J Gastrointest Oncol 2011; 2: 151-156.
42. Mini E, Nobili S, Caciagli B, Landini I, Mazzei T. Cellular pharmacology of gemcitabine. Ann Oncol 2006; 17(suppl 5): v7-v12. (Pubitemid 43994854)
43. Regine W, Winter K, Abrams R, Safran H, Hoffman J, Konski A et al. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol 2011; 18: 1319-1326.
44. Farrell J, Elsaleh H, Garcia M, Lai R, Ammar A, Regine W et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology 2009; 136: 187-195.
45. Giovannetti E, Del Tacca M, Mey V, Funel N, Nannizzi S, Ricci S et al. Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res 2006; 66: 3928-3935.
46. A phase II randomized, open-label, multicenter study comparing CO-1.01 with gemcitabine as first-line therapy in patients with metastatic pancreatic adenocarcinoma. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited 19 July 2011]. Available from: http://clinicaltrials.gov/show/NCT0112478/NLMIdentifier:NCT01124786.
47. A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 for infusion as second-line therapy for gemcitabine- refractory patients with stage IV pancreatic adenocarcinoma and no tumor hENT1 expression. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 2011]. Available from: http://clinicaltrials. gov/show/NCT01233375/NLMIdentifier:NCT01233375.
48. Sebastiani V, Ricci F, Rubio-Viqueira B, Kulesza P, Yeo CJ, Hidalgo M et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res 2006; 12: 2492-2497. (e-pub 28 April 2006).
49. Candelaria M, de la Cruz-Hernández E, Pérez-Cárdenas E, Trejo-Becerril C, Gutiérrez-Hernández O, Dueñas- González A. Pharmacogenetics and pharmacoepigenetics of gemcitabine. Med Oncol 2010; 27: 1133-1143.
50. Ueno H, Kaniwa N, Okusaka T, Ikeda M, Morizane C, Kondo S et al. Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients. Br J Cancer 2009; 100: 870-873.
51. Sugiyama E, Kaniwa N, Kim S-R, Kikura Hanajiri R, Hasegawa R, Maekawa K et al. Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism. J Clin Oncol 2007; 25: 32-42. (Pubitemid 350003048)
52. Ciccolini J, Dahan L, Andre N, Evrard A, Duluc M, Blesius A et al. Cytidine deaminase residual activity in serum is a predictive marker of early severe toxicities in adults after gemcitabine-based chemotherapies. J Clin Oncol 2010; 28: 160-165. (e-pub 26 November 2009).
53. Farrell JJ, Bae K, Wong J, Guha C, Dicker AP, Elsaleh H. Cytidine deaminase single-nucleotide polymorphism is predictive of toxicity from gemcitabine in patients with pancreatic cancer: RTOG 9704. Pharmacogenomics J 2011 (e-pub 1 June 2011).
54. Bengala C, Guarneri V, Giovannetti E, Lencioni M, Fontana E, Mey V et al. Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma. Br J Cancer 2005; 93: 35-40. (Pubitemid 41076250)
55. Kroep JR, Loves WJ, van der Wilt CL, Alvarez E, Talianidis I, Boven E et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity. Mol Cancer Ther 2002; 1: 371-376. (e-pub 13 December 2002).
56. Winder T, Lenz HJ. Molecular predictive and prognostic markers in colon cancer. Cancer Treat Rev 2010; 36: 550-556. (e-pub 7 April 2010).
57. Yen CC, Chen YJ, Lu KH, Hsia JY, Chen JT, Hu CP et al. Genotypic analysis of esophageal squamous cell carcinoma by molecular cytogenetics and real-time quantitative polymerase chain reaction. Int J Oncol 2003; 23: 871-881. (e-pub 10 September 2003).
58. Nakayama S, Takeda S, Kawase Y, Inoue S, Kaneko T, Nakao A. Clinical significance of dihydropyrimidine dehydrogenase in adjuvant 5-fluorouracil liver perfusion chemotherapy for pancreatic cancer. Ann Surg 2004; 240: 840-844. (Pubitemid 39425777)
59. Zhou W, Gurubhagavatula S, Liu G, Park S, Neuberg DS, Wain JC et al. Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res 2004; 10: 4939-4943. (e-pub 7 August 2004). (Pubitemid 39099767)
60. Yin M, Yan J, Martinez-Balibrea E, Graziano F, Lenz HJ, Kim HJ et al. ERCC1 and ERCC2 polymorphisms predict clinical outcomes of oxaliplatin-based chemotherapies in gastric and colorectal cancer: a systemic review and meta-analysis. Clin Cancer Res 2011; 17: 1632-1640. (e-pub 1 February 2011).
61. Shirota Y, Stoehlmacher J, Brabender J, Xiong YP, Uetake H, Danenberg KD et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 2001; 19: 4298-4304. (e-pub 4 December 2001) (Pubitemid 33096777)
62. Mancuso A, Sacchetta S, Saletti PC, Tronconi C, Milesi L, Garassino M et al. Clinical and molecular determinants of survival in pancreatic cancer patients treated with second-line chemotherapy: results of an Italian/Swiss multicenter survey. Anticancer Res 2010; 30: 4289-4295. (e-pub 3 November 2010).
63. Maithel SK, Coban I, Kneuertz PJ, Kooby DA, El-Rayes BF, Kauh JS et al. Differential expression of ERCC1 in pancreas adenocarcinoma: high tumor expression is associated with earlier recurrence and shortened survival after resection. Ann Surg Oncol 2011 (e-pub 2 March 2011).
64. Marsh S, Hoskins JM. Irinotecan pharmacogenomics. Pharmacogenomics 2010; 11: 1003-1010. (e-pub 7 July 2010).
65. Yan Q, Sage EH. SPARC, a matricellular glycoprotein with important biological functions. J Histochem Cytochem 1999; 47: 1495-1506.
66. Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 2001; 107: 1049-1054. (Pubitemid 32422898)
67. Sato N, Fukushima N, Maehara N, Matsubayashi H, Koopmann J, Su G et al. SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene 2003; 22: 5021-5030. (Pubitemid 37026400)
68. Infante J, Matsubayashi H, Sato N, Tonascia J, Klein A, Riall T et al. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol 2007; 25: 319-325. (Pubitemid 350003021)
69. Mantoni T, Schendel RRE, Rdel F, Niedobitek G, Al Assar O, Masamune A et al. Stromal SPARC expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. Cancer Biology Ther 2008; 7: 1806-1815.
70. Miyoshi K, Sato N, Ohuchida K, Mizumoto K, Tanaka M. SPARC mRNA expression as a prognostic marker for pancreatic adenocarcinoma patients. Anticancer Res 2010; 30: 867-871.
71. Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 2006; 12: 1317-1324. (Pubitemid 43342524)
72. Desai N, Trieu V, Hwang L, Wu R, Soon Shiong P, Gradishar W. Improved effectiveness of nanoparticle albumin-bound (nab) paclitaxel versus polysorbate-based docetaxel in multiple xenografts as a function of HER2 and SPARC status. Anticancer Drugs 2008; 19: 899-909.
73. VonHoff D. Epithelium and stroma: double trouble progress in pancreatic cancer session April 18 at the 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC 2010.
74. Von Hoff DD, Ramanathan R, Borad M, Laheru D, Smith L, Wood T et al, editor. SPARC correlation with response to gemcitabine plus nabpaclitaxel in patients with advanced metastatic pancreatic cancer. ASCO Annual Conference 2009.
75. Olive K, Jacobetz M, Davidson C, Gopinathan A, McIntyre D, Honess D et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324: 1457-1461.
76. Sidney Kimmel Comprehensive Cancer Center. A phase II study of gemcitabine and nab-paclitaxel in combination with GDC-0449 (Hedgehog inhibitor) in patients with previously untreated metastatic adenocarcinoma of the pancreas. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited 29 March 2011]. Available from: http:// clinicaltrials.gov/show/NCT01088815NLMIdentifier:NCT01088815.
77. Biankin AV, Kench JG, Colvin EK, Segara D, Scarlett CJ, Nguyen NQ et al. Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer. Gastroenterology 2009; 137: 558-568, , 68 e1-11. (e-pub 21 April 2009).
78. Tempero M. S100A2 as a prognostic marker in patients receiving adjuvant therapy for pancreatic cancer (PC): a secondary analysis of RTOG 9704. J Clin Oncol 2011; 29(suppl 15): 4118.
79. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S 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. (Pubitemid 46972777)
80. Zakowski MF, Ladanyi M, Kris MG. EGFR mutations in small-cell lung cancers in patients who have never smoked. N Engl J Med 2006; 355: 213-215. (e-pub 14 July 2006). (Pubitemid 44050422)
81. da Cunha Santos G, Dhani N, Tu D, Chin K, Ludkovski O, Kamel-Reid S et al. Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Canada Clinical Trials Group Study PA3. Cancer 2010; 116: 5599-5607. (e-pub 9 September 2010).
82. RTOG-0848. A phase III trial evaluating both erlotinib and chemoradiation as adjuvant treatment for patients with resected head of pancreas adenocarcinoma. In: clinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 2011]. Available from: http://clinicaltrials.gov/show/NCT01013649/NLMIdentifier:NCT01013649.