Seminars in Radiation Oncology
Volume 17, Issue 1 , Pages 62-69 , January 2007

Targeted Agents and Esophageal Cancer—The Next Step?

  • Mebea Aklilu, MD

      Affiliations

    • Wake Forest University, Winston-Salem, NC.
    • Corresponding Author InformationAddress reprint requests to Mebea Aklilu, Medical Center Blvd, Winston-Salem, NC 27157.
    • ,
  • David H. Ilson, MD

      Affiliations

    • Memorial Sloan-Kettering Cancer Center, New York, NY.

References 

  1. Parkin DM. International variation. Oncogene. 2004;23:6329–6340
  2. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10–30
  3. Blot WJ, McLaughlin JK. The changing epidemiology of esophageal cancer. Semin Oncol. 1999;26(suppl 15):2–8
  4. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–2252
  5. Herbst RS, Shin DM. Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: A new paradigm for cancer therapy. Cancer. 2002;94:1593–1611
  6. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19:183–232
  7. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–137
  8. Gullick WJ. Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers. Br Med Bull. 1991;47:87–98
  9. Schlessinger J. The epidermal growth factor receptor as a multifunctional allosteric protein. Biochemistry. 1988;27:3119–3123
  10. Ennis BW, Lippman ME, Dickson RB. The EGF receptor system as a target for antitumor therapy. Cancer Invest. 1991;9:553–562
  11. Mayer A, Takimoto M, Fritz E, et al. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer. 1993;71:2454–2460
  12. Rubin Grandis J, Melhem MF, Gooding WE, et al. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst. 1998;90:824–832
  13. Bauknecht T, Runge M, Schwall M, et al. Occurrence of epidermal growth factor receptors in human adnexal tumors and their prognostic value in advanced ovarian carcinomas. Gynecol Oncol. 1988;29:147–157
  14. Wu X, Fan Z, Masui H, et al. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest. 1995;95:1897–1905
  15. Prewett M, Rockwell P, Rockwell RF, et al. The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma. J Immunother Emphasis Tumor Immunol. 1996;19:419–427
  16. Herbst RS, Fukuoka M, Baselga J. Gefitinib—A novel targeted approach to treating cancer. Nat Rev Cancer. 2004;4:956–965
  17. Balaban N, Moni J, Shannon M, et al. The effect of ionizing radiation on signal transduction: Antibodies to EGF receptor sensitize A431 cells to radiation. Biochim Biophys Acta. 1996;1314:147–156
  18. Chinnaiyan P, Huang S, Vallabhaneni G, et al. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res. 2005;65:3328–3335
  19. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–345
  20. Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23:8646–8654
  21. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–578
  22. Enzinger PC, Yock T, Suh W, et al. Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for advanced esophageal cancer. J Clin Oncol. 2006;24(18s):194s;(suppl 4064)
  23. Vanhoefer U, Tewes M, Rojo F, et al. Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J Clin Oncol. 2004;22:175–184
  24. Foon KA, Yang XD, Weiner LM, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004;58:984–990
  25. Kris MG, Natale RB, Herbst RS, 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. JAMA. 2003;290:2149–2158
  26. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial). [corrected] J Clin Oncol. 2003;21:2237–2246
  27. Perez-Soler R. Phase II clinical trial data with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (OSI-774) in non-small-cell lung cancer. Clin Lung Cancer. 2004;6(suppl 1):S20–S23
  28. Tew WP, Shah M, Schwartz G, et al. Phase II trial or erlotinib for second-line treatment in advanced esophageal cancer. Proc Am Soc Clin Oncol GI Cancers Symposium. 2005;23:5;(abstr)
  29. Dragovich T, McCoy S, Urba SG, et al. SWOG 0127: Phase II trial of erlotinib in GEJ and gastric adenocarcinomas. Proc Am Soc Clin Oncol GI Cancers Symposium. 2005;23:49;(abstr)
  30. Ferry DR, Anderson M, Beddows K, et al. Phase II trial of gefitinib (ZD 1839) in advanced adenocarcinoma of the oesophagus incorparating biopsy before and after gefitinib. J Clin Oncol. 2004;22:4021;(suppl, abstr)
  31. Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol. 2006;24:1612–1619
  32. Doi T, Koizumi W, Siena S, et al. Efficacy, tolerability and pharmacokinetics of gefitinib (ZD 1839) in pretreated patients with metastatic gastric cancer. Proc Am Soc Clin Oncol. 2003;22:258;(abstr 1036)
  33. Thatcher N, Chang A, Parikh P, 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;366:1527–1537
  34. Herbst RS, Giaccone G, Schiller JH, 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;22:785–794
  35. Giaccone G, Herbst RS, Manegold C, 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;22:777–784
  36. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–132
  37. Cappuzzo F, Gregorc V, Rossi E, et al. Gefitinib in pretreated non-small-cell lung cancer (NSCLC): Analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. J Clin Oncol. 2003;21:2658–2663
  38. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med. 2005;353:133–144
  39. Lynch TJ, Bell DW, Sordella R, 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;350:2129–2139
  40. Chung KY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005;23:1803–1810
  41. Moroni M, Veronese S, Benvenuti S, et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: A cohort study. Lancet Oncol. 2005;6:279–286
  42. Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005;97:643–655
  43. Slamon DJ, Clark GM. Amplification of c-erbB-2 and aggressive human breast tumors?. Science. 1988;240:1795–1798
  44. Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001;19:554–568
  45. Safran H, DiPetrillo T, Nadeem A, et al. Trastuzumab, paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus: A phase I study. Cancer Invest. 2004;22:670–677
  46. Papetti M, Herman IM. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol. 2002;282:C947–C970
  47. Longo R, Sarmiento R, Fanelli M, et al. Anti-angiogenic therapy: Rationale, challenges and clinical studies. Angiogenesis. 2002;5:237–256
  48. North S, Moenner M, Bikfalvi A. Recent developments in the regulation of the angiogenic switch by cellular stress factors in tumors. Cancer Lett. 2005;218:1–14
  49. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–1027
  50. Ostman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004;15:275–286
  51. Pietras K, Sjoblom T, Rubin K, et al. PDGF receptors as cancer drug targets. Cancer Cell. 2003;3:439–443
  52. Cao Y. Direct role of PDGF-BB in lymphangiogenesis and lymphatic metastasis. Cell Cycle. 2005;4:228–230
  53. Toi M, Matsumoto T, Bando H. Vascular endothelial growth factor: Its prognostic, predictive, and therapeutic implications. Lancet Oncol. 2001;2:667–673
  54. Kleespies A, Guba M, Jauch KW, et al. Vascular endothelial growth factor in esophageal cancer. J Surg Oncol. 2004;87:95–104
  55. Auvinen MI, Sihvo EI, Ruohtula T, et al. Incipient angiogenesis in Barrett’s epithelium and lymphangiogenesis in Barrett’s adenocarcinoma. J Clin Oncol. 2002;20:2971–2979
  56. Lord RV, Park JM, Wickramasinghe K, et al. Vascular endothelial growth factor and basic fibroblast growth factor expression in esophageal adenocarcinoma and Barrett esophagus. J Thorac Cardiovasc Surg. 2003;125:246–253
  57. Couvelard A, Paraf F, Gratio V, et al. Angiogenesis in the neoplastic sequence of Barrett’s oesophagus (Correlation with VEGF expression). J Pathol. 2000;192:14–18
  58. Kulke MH, Odze RD, Mueller JD, et al. Prognostic significance of vascular endothelial growth factor and cyclooxygenase 2 expression in patients receiving preoperative chemoradiation for esophageal cancer. J Thorac Cardiovasc Surg. 2004;127:1579–1586
  59. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342
  60. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004;22:2184–2191
  61. Shah M, Ramanathan RK, Ilson DH, et al. Final results of a muticenter phase II study of irinotecan (CPT), cisplatin (CIS), and bevacizumab (BEV) in patients with unresectable or metastatic gastric or gastroesophageal (GEJ) adenocarcinoma. J Clin Oncol. 2006;24(18s):183s;(suppl 4020)
  62. Enzinger PC, Fidias P, Meyerhardt J, et al. Phase II study of Bevacizumab and Docetaxel in metastatic esophageal and gastric cancer. Proc Am Soc Clin Oncol GI Cancers Symposium. 2006;68:118;(abstr)
  63. Kozin SV, Boucher Y, Hicklin DJ, et al. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res. 2001;61:39–44
  64. Geng L, Donnelly E, McMahon G, et al. Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res. 2001;61:2413–2419
  65. Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–147
  66. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:16–24
  67. Escudier B, Sczylik C, Eisen T, et al. Randomized phase III trial of the Ras kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Proc Am Soc Clin Oncol. 2005;23:LBA4510;(abstr)
  68. Rini BI, Rixe O, Bukowski RM, et al. AG-013736, a multi-target tyrisine kinase inhibitor, demonstrates anti-tumor activity in a phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). Proc Am Soc Clin Oncol. 2005;23(16s):380s;(suppl 4509)
  69. Baldwin AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683
  70. Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179
  71. Barnes PJ, Karin M. Nuclear factor-kappaB: A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066–1071
  72. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996;274:782–784
  73. Abdel-Latif MM, O’Riordan J, Windle HJ, et al. NF-kappaB activation in esophageal adenocarcinoma: Relationship to Barrett’s metaplasia, survival, and response to neoadjuvant chemoradiotherapy. Ann Surg. 2004;239:491–500
  74. Izzo JG, Malhotra U, Wu TT, et al. Association of activated transcription factor nuclear factor kappab with chemoradiation resistance and poor outcome in esophageal carcinoma. J Clin Oncol. 2006;24:748–754
  75. Shah M, Holen K, Singh D, et al. A multicenter, two-stage, phase II study pf PS-341 in patients with unresectable metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Proc Am Soc Clin Oncol GI Cancers Symposium. 2005;41:103;(abstr)
  76. Shirvani VN, Ouatu-Lascar R, Kaur BS, et al. Cyclooxygenase 2 expression in Barrett’s esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology. 2000;118:487–496
  77. Thun MJ, Namboodiri MM, Calle EE, et al. Aspirin use and risk of fatal cancer. Cancer Res. 1993;53:1322–1327
  78. Li M, Lotan R, Levin B, et al. Aspirin induction of apoptosis in esophageal cancer: A potential for chemoprevention. Cancer Epidemiol Biomarkers Prev. 2000;9:545–549
  79. Rubio CA. Antitumoral activity of indomethacin on experimental esophageal tumors. J Natl Cancer Inst. 1984;72:705–707
  80. Rubio CA. Further studies on the therapeutic effect of indomethacin on esophageal tumors. Cancer. 1986;58:1029–1031
  81. Pillsbury HC, Webster WP, Rosenman J. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers. Arch Otolaryngol Head Neck Surg. 1986;112:552–553
  82. Milas L, Hanson WR. Eicosanoids and radiation. Eur J Cancer. 1995;31A:1580–1585
  83. Kishi K, Petersen S, Petersen C, et al. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res. 2000;60:1326–1331
  84. Govindan R, Fineberg N, McLeod H, et al. A phase II study of cisplatin, 5 fluorouracil (5 FU), radiation (RT), and celecoxib in patients with resectable esophageal cancer (EC): Updated results from the Hoosier Oncology Group (HOG) Study. J Clin Oncol. 2004;22(14s):326s;(suppl 4052)
  85. Enzinger PC, Mamon H, Choi N, et al. Phase II cisplatin, irinotecan, celecoxib and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer. Gastrintestinal Cancers Symposium. 2004;35:59;(abstr)

PII: S1053-4296(06)00078-6

doi: 10.1016/j.semradonc.2006.09.006

Seminars in Radiation Oncology
Volume 17, Issue 1 , Pages 62-69 , January 2007

Article Tools