Skip to main content
SpringerLink
Log in

Systemic Treatment of Esophageal Cancer

  • Chapter
  • First Online:
Principles and Practice of Radiotherapy Techniques in Thoracic Malignancies

  • 1094 Accesses

Abstract

The incidence and prevalence of esophageal cancer is increasing in the Western world, and the increase is primarily due to an increase in the rate of adenocancer of the distal esophagus (Devesa et al. Cancer 83:2049–2053, 1998). In many institutions, esophageal adenocarcinomas outnumber squamous cell esophageal cancers (SCC). Due to the marked differences in the pathogenesis, biology, and characteristics of these distinct two cancers, SCC and adenocancer of the esophagus must be treated as separate entities and thus managed differently (Stein et al. Surg Clin N Am 80:659–682, 2000). Despite the advances in the surgical management of SCC and adenocancer of the esophagus, and the use of adjunctive treatments, the overall disease prognosis remains dismal. Improvement in the survival of these patients will most likely depend on the development of individualized, tailored therapeutic strategies based on molecular biology, tumor genetics, and better patient characterization.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Devesa SS, Blot WJ, Fraumeni Jr JF. Changing patterns in the incidence of esophageal and gastric adenocarcinoma in the U.S. Cancer. 1998;83:2049–53.

    Article  CAS  PubMed  Google Scholar 

  2. Stein SJ, Sendler A, Fink U, et al. Multidisciplinary approach to esophageal and gastric cancer. Surg Clin North Am. 2000;80:659–82.

    Article  CAS  PubMed  Google Scholar 

  3. Ajani JA, Barthel JS, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers. J Natl Compr Canc Netw. 2011;9:830–87.

    PubMed  Google Scholar 

  4. D’Amico TA. Surgery for esophageal cancer. Gastrointest Cancer Res. 2008;2:S6–9.

    PubMed  PubMed Central  Google Scholar 

  5. Graham AJ, Shrive FM, Ghali WA, et al. Defining the optimal treatment of locally advanced esophageal cancer: a systematic review and decision analysis. Ann Thorac Surg. 2007;83:1257–64.

    Article  PubMed  Google Scholar 

  6. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.

    Article  CAS  PubMed  Google Scholar 

  7. Horner M, Ries L, Krapcho M, et al. SEER cancer statistics review, 1975–2006, National Cancer Institute. Bethesda. Available online: http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site. 2009.

  8. Berry MF. Esophageal cancer: staging system and guidelines for staging and treatment. J Thorac Dis. 2014;6 Suppl 3:S289–97.

    PubMed  PubMed Central  Google Scholar 

  9. Mannell A, Winters Z. Carboplatin in the treatment of esophageal cancer. S Afr Med J. 1989;76:213–4.

    CAS  PubMed  Google Scholar 

  10. Sternberg C, Kelsen D, Dukeman M, et al. Carboplatin: a new platin analog in the treatment of epidermoid carcinoma of the esophagus. Cancer Treat Rep. 1985;69:1305–7.

    CAS  PubMed  Google Scholar 

  11. Albertsson M, Fagerberg J, Jacobsen A, et al. Preliminary results of a phase 2 study with Taxotere (docetaxel) in patients with primary untreated or recurrent esophagus cancer. Proc ASCO. 2000;19:A1218. abst.

    Google Scholar 

  12. Panettiere FJ, Leichman L, O’Bryan R, et al. Cis-diam-minedichloride platinum (II), an effective agent in the treatment of epidermoid carcinoma of the esophagus. A preliminary report of an ongoing SWOG study. Cancer Clin Trials. 1981;4:29–31.

    CAS  PubMed  Google Scholar 

  13. Ravry MJ, Moore MR, Omura GA, et al. Phase II evaluation of cisplatin in squamous carcinoma of the esophagus: a Southeastern Cancer Study Group trial. Cancer Treat Rep. 1985;69:1457–8.

    CAS  PubMed  Google Scholar 

  14. Davis S, Shanmugathasa M, Kessler W. Cis-diam-minedichloride platinum (II)in the treatment of esophageal carcinoma. Cancer Treat Rep. 1980;69:709–11.

    Google Scholar 

  15. Murthy SK, Prabkaharan PS, Chandrashekar M, et al. Neoadjuvant Cis-DDP in esophageal cancers: an experience at a regional cancer center, India. J Surg Oncol. 1990;45:173–6.

    Article  CAS  PubMed  Google Scholar 

  16. Ajani J, Kantarjian H, Kanojia M, et al. Phase II trial of cis-platinum in advanced upper gastrointestinal cancer. Proc ASCO. 1984;2, C-573.

    Google Scholar 

  17. Stephens FO. Bleomycin-a new approach in cancer chemotherapy. Med J Aust. 1973;1:1277–83.

    CAS  PubMed  Google Scholar 

  18. Bonadonna G, De Lena M, Monfardini S, et al. Clinical trials with bleomycin in lymphomas and in solid tumors. Eur J Cancer. 1972;8:205–15.

    Article  CAS  PubMed  Google Scholar 

  19. Ravry M, Moertel CG, Schutt AJ, et al. Treatment of advanced SCC of the gastrointestinal tract with bleomycin. Cancer Chemother Rep. 1973;57:493–5.

    CAS  PubMed  Google Scholar 

  20. Engstrom PF, Lavin PT, Klaassen DJ, et al. phase II evaluation of mitomycin and cisplatin in advanced esophageal carcinoma. Cancer Treat Rep. 1983;67:713–5.

    CAS  PubMed  Google Scholar 

  21. Whittington RM, Close HP. Clinical experience with mitomycin C. Cancer Chemother Rep. 1970;54:195–8.

    CAS  PubMed  Google Scholar 

  22. Ezdinli EZ, Gelber R, Desai DV, et al. Chemotherapy of advanced esophageal carcinoma: ECOG experience. Cancer. 1980;46:2149–53.

    Article  CAS  PubMed  Google Scholar 

  23. Harstrick A, Bokemayer C, Preusser P, et al. Phase II study of single agent etoposide in patients with metastatic SCC of the esophagus. Cancer Chemother Pharmacol. 1992;29:321–2.

    Article  CAS  PubMed  Google Scholar 

  24. Kelsen DP, Bains M, Cvitkovic E, et al. Vindesine in the treatment of esophageal carcinoma: a phase II study. Cancer Treat Rep. 1979;63:2019–21.

    CAS  PubMed  Google Scholar 

  25. Conroy T, Etienne PL, Adenis A, et al. Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. EORTC Gastrointestinal Cancer Cooperative Group. J Clin Oncol. 1996;14:164–70.

    CAS  PubMed  Google Scholar 

  26. Ajani JA, Ilson DH, Daugherty K, et al. Activity of taxol in patients with SCC and AC of the esophagus. J Natl Cancer Inst. 1994;86:1086–91.

    Article  CAS  PubMed  Google Scholar 

  27. Slabber CF, Falkson CI, Musi NNM, et al. A phase II study of docetaxel in advanced, inoperable squamous carcinoma of the esophagus. Proc ASCO. 1999;18, A1151.

    Google Scholar 

  28. Lin L, Hecht J. A phase II trial of irinotecan in patients with advanced adenocarcinoma of the GE junction. Proc ASCO. 2000;19, 1130.

    Google Scholar 

  29. National Cancer Institute. http.www.cancer.gov/drugdictionary.

  30. Ilson DH, Kelsen DP. Chemotherapy in esophageal cancer. Anticancer Drugs. 1993;4:287–99.

    Article  CAS  PubMed  Google Scholar 

  31. De Besi P, Sileni VC, Salvagno L, et al. Phase II study of cisplatin, 5-FU and allopurinol in advanced esophageal cancer. Cancer Treat Rep. 1986;70:909–10.

    PubMed  Google Scholar 

  32. Bleiberg H, Conroy T, Paillot B, et al. Randomized phase II study of cisplatin and 5-FU vs cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer. 1997;33:1216–20.

    Article  CAS  PubMed  Google Scholar 

  33. Iizuka T, Kakegawa T, Ide H, et al. Phase II evaluation of cisplatin and 5-FU in advanced squamous cell carcinoma of the esophagus: A Japanese Esophageal Oncology Group Trial. Jpn J Clin Oncol. 1992;22:172–6.

    CAS  PubMed  Google Scholar 

  34. Zaniboni A, Simoncini E, Tonini G, et al. Cisplatin, high-dose folinic acid and 5-FU in squamous cell carcinoma of the esophagus. A pilot study. Chemioterapia. 1987;6:387–9.

    CAS  PubMed  Google Scholar 

  35. Feliu J, Gonzales BM, Garcia GC, et al. Phase II study of cisplatin, 5-FU, and leukovorin in inoperable squamous cell carcinoma of the esophagus. ONCOPAZ Cooperative Group, Spain. Am J Clin Oncol. 1996;19:577–80.

    Article  CAS  PubMed  Google Scholar 

  36. Ilson DH, Ajani J, Bhalla K, et al. Phase II trial of paclitaxel, 5-FU, and cisplatin in patients with advanced carcinoma of the esophagus. J Clin Oncol. 1998;16:1826–34.

    CAS  PubMed  Google Scholar 

  37. Ilson DH, Saltz L, Enzinger P, et al. Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol. 1999;17:3270–5.

    CAS  PubMed  Google Scholar 

  38. Wang J, Chang J, Yu H, et al. A phase II study of oxaliplatin in combination with leucovorin and fluorouracil as first-line chemotherapy in patients with metastatic squamous cell carcinoma in esophagus. Cancer Chemother Pharmacol. 2013;71:905–11.

    Article  CAS  PubMed  Google Scholar 

  39. Conroy T, Galais MP, Raoul JL, et al. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with esophageal cancer (PRODIGE5/ ACCORD17): Final results of a randomized, phase 2/3 trial. Lancet Oncol. 2014;15:305–14.

    Article  CAS  PubMed  Google Scholar 

  40. Ilson DH. Esophageal cancer chemotherapy: recent advances. Gastrointest Cancer Res. 2008;2:85–92.

    PubMed  PubMed Central  Google Scholar 

  41. Thallinger CMR, Raderer M, Hejna M. Esophageal cancer: a critical evaluation of systemic second-line therapy. J Clin Oncol. 2011;29:4709–14.

    Article  CAS  PubMed  Google Scholar 

  42. Lorenzen S, Duyster J, Lersch C, et al. Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial. Br J Cancer. 2005;92:2129–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lordick F, von Schilling C, Bernhard H, et al. Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer. Br J Cancer. 2003;89:630–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Burtness B, Gibson M, Egleston B, et al. Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer. Ann Oncol. 2009;20:1242–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shim HJ, Cho SH, Hwang JE, et al. Phase II study of docetaxel and cisplatin chemotherapy in 5-fluorouracil/cisplatin pretreated esophageal cancer. Am J Clin Oncol. 2010;33:624–8.

    Article  CAS  PubMed  Google Scholar 

  46. Mafune K, Yamada K, Imamura K, et al. Docetaxel, 5-fluorouracil and nedaplatin as second-line chemotherapy for patients with esophageal cancer after esophagectomy: a pilot study. J Clin Oncol. 2006;24(suppl):635s. abstr 14140.

    Google Scholar 

  47. Yoshioka T, Sakayori M, Kato S, et al. Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation. Int J Clin Oncol. 2006;11:454–60.

    Article  CAS  PubMed  Google Scholar 

  48. Nakajima Y, Suzuki T, Haruki S, et al. A pilot trial of docetaxel and nedaplatin in cisplatin-pretreated relapsed or refractory esophageal squamous cell cancer. Hepatogastroenterology. 2008;55:1631–5.

    CAS  PubMed  Google Scholar 

  49. Jin J, Xu X, Wang F, et al. Second-line combination chemotherapy with docetaxel and nedaplatin for cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma. J Thorac Oncol. 2009;4:1017–21.

    Article  PubMed  Google Scholar 

  50. Osaka Y, Takagi Y, Hoshino S, et al. Combination chemotherapy with docetaxel and nedaplatin for recurrent esophageal cancer in an outpatient setting. Dis Esophagus. 2006;19:473–6.

    Article  CAS  PubMed  Google Scholar 

  51. Kanai M, Matsumoto S, Nishimura T, et al. Retrospective analysis of 27 consecutive patients treated with docetaxel/nedaplatin combination therapy as a second-line regimen for advanced esophageal cancer. Int J Clin Oncol. 2007;12:224–7.

    Article  CAS  PubMed  Google Scholar 

  52. Tanaka T, Fujita H, Sueyoshi S, et al. Second-line combination chemotherapy with docetaxel for cisplatin-pretreated refractory metastatic esophageal cancer: a preliminary report of initial experience. Chemotherapy. 2007;53:449–53.

    Article  CAS  PubMed  Google Scholar 

  53. Minamide J, Aoyama N, Takada K, et al. Evaluation of docetaxel, CDDP and 5-FU combined therapy as second-line chemotherapy for esophagus cancer [In Japanese]. Gan To Kagaku Ryoho. 2007;34:49–52.

    PubMed  Google Scholar 

  54. Park BB, Im YH, Hwang IG, et al. Salvage chemotherapy with mitomycin C, ifosfamide, and cisplatin (MIC) for previously treated metastatic or recurrent esophageal squamous cell carcinoma. Invest New Drugs. 2008;26:387–92.

    Article  CAS  PubMed  Google Scholar 

  55. Medical Research Council Oesophageal Cancer Working Party. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002;359:1727–33.

    Article  Google Scholar 

  56. Le Prise E, Etienne PL, Meunier B, et al. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus. Cancer. 1994;73:1779–84.

    Article  PubMed  Google Scholar 

  57. Smith TJ, Ryan LM, Douglass Jr HO, et al. Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys. 1998;42:269–76.

    Article  CAS  PubMed  Google Scholar 

  58. Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal cancer. JAMA. 1999;281:1623–7.

    Article  CAS  PubMed  Google Scholar 

  59. Slabber CF, Nel JS, Schoeman L, et al. A randomized study of radiotherapy alone versus radiotherapy plus 5-fluorouracil and platinum in patients with inoperable, locally advanced squamous cancer of the esophagus. Am J Clin Oncol. 1998;21:462–5.

    Article  CAS  PubMed  Google Scholar 

  60. Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335:462–7.

    Article  CAS  PubMed  Google Scholar 

  61. Bosset J-F, Gignoux M, Triboulet J-P, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997;337:161–7.

    Article  CAS  PubMed  Google Scholar 

  62. Urba S, Orringer M, Turrisi A, et al. Randomized preoperative locoregional chemoradiation versus surgery alone in patients with resectable esophageal cancer. J Clin Oncol. 2001;19:305–13.

    CAS  PubMed  Google Scholar 

  63. Burmeister BH, Smithers BM, Fitzgerald L, et al. A randomized phase III trial of preoperative chemoradiation followed by surgery *CR-S) versus surgery alone (S) for localized resectable cancer of the esophagus [abstract]. Proc Am Soc Clin Oncol. 2002;21:130a.

    Google Scholar 

  64. Chau I, Norman AR, Cunningham D, et al. The impact of primary tumour origins in patients with advanced oesophageal, oesophago-gastric junction and gastric adenocarcinoma: individual patient data from 1775 patients in four randomised controlled trials. Ann Oncol. 2009;20:885–91.

    Article  CAS  PubMed  Google Scholar 

  65. Glimelius B, Ekström K, Hoffman K, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997;8:163–8.

    Article  CAS  PubMed  Google Scholar 

  66. Murad A, Santiago F, Petroianu A, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993;72:37–41.

    Article  CAS  PubMed  Google Scholar 

  67. Pyrhönen S, Kuitunen T, Nyandoto P, et al. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer. 1995;71:587–91.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ford HE, Marshall A, Bridgewater JA, et al. Docetaxel versus active symptom control for refractory oesophageal adenocarcinoma (COUGAR-02): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2014;15:78–86.

    Article  CAS  PubMed  Google Scholar 

  69. Kang JH, Lee SI, Lim dH, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012;30:1513–8.

    Article  CAS  PubMed  Google Scholar 

  70. Thuss-Patience PC, Kretzschmar A, Deist T, et al. Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: a randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). J Clin Oncol. 2009;27(suppl):211s. abstr 4540.

    Google Scholar 

  71. Wagner AD, Grothe W, Haerting J, et al. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–9.

    Article  CAS  PubMed  Google Scholar 

  72. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 study group. J Clin Oncol. 2006;24:4991–7.

    Article  PubMed  CAS  Google Scholar 

  73. Guimbaud R, Louvet C, Ries P, et al. Prospective, randomized, multicenter phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma fluorouracil: a French intergroup (Federation Francophone de Cancerologie Digestive, Federation Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014;32:3520–6.

    Article  CAS  PubMed  Google Scholar 

  74. Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.

    Article  CAS  PubMed  Google Scholar 

  75. Ajani JA, Rodriguez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010;28:1547–53.

    Article  CAS  PubMed  Google Scholar 

  76. Al-Batran SE, Hartmann JT, Probst S, et al. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008;26:1435–42.

    Article  CAS  PubMed  Google Scholar 

  77. Kang YK, Kang WK, Shin DB, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20:666–73.

    Article  PubMed  Google Scholar 

  78. Ilson DH. Docetaxel, cisplatin, and fluorouracil in gastric cancer: does the punishment fit the crime? J Clin Oncol. 2007;25:3188–90.

    Article  CAS  PubMed  Google Scholar 

  79. Lorenzen S, Hentrich M, Haberl C, et al. Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: results of a phase II trial. Ann Oncol. 2007;18:1673–9.

    Article  CAS  PubMed  Google Scholar 

  80. Tebbutt NC, Cummins MM, Sourjina T, et al. Randomised, non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer: the AGITG ATTAX trial. Br J Cancer. 2010;102:475–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Shah MA, Stoller R, Shibata S, et al. Random assignment multicenter phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF) versus DCF with growth factor support (GCSF) in metastatic gastroesophageal adenocarcinoma (GE). J Clin Oncol. 2010;28(suppl):304s. abstr 4014.

    Google Scholar 

  82. Power DG, Kelsen DP, Shah MA. Advanced gastric cancer: slow but steady progress. Cancer Treat Rev. 2010;36:384–92.

    Article  PubMed  Google Scholar 

  83. Iacovelli R, Pietrantonio F, Farcomeni A, et al. Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer. A systemic review and meta-analysis of published studies. PLoS One. 2014;9, e108940.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Gu J, Ajani JA, Hawk ET, et al. Genome-wide catalogue of chromosomal aberrations in Barrett’s esophagus and esophageal adenocarcinoma: a high-density single nucleotide polymorphism array analysis. Cancer Prev Res (Phila). 2010;3:1176–86.

    Article  CAS  Google Scholar 

  85. Varis A, Puolakkainen P, Savolainen H, et al. DNA copy number profiling in esophageal Barrett adenocarcinoma: comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma. Cancer Genet Cytogenet. 2001;127:53–8.

    Article  CAS  PubMed  Google Scholar 

  86. Bang YJ, Van Gutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2- positive advanced gastric or gastrooesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.

    Article  CAS  PubMed  Google Scholar 

  87. Reid BJ, Prevo LJ, Galipeau PC, et al. Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol. 2001;96:2839–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hollstein MC, Metcalf RA, Welsh JA, et al. Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci U S A. 1990;87:9958–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Casson AG, Mukhopadhyay T, Cleary KR, et al. p53 gene mutations in Barrett’s epithelium and esophageal cancer. Cancer Res. 1991;51:4495–9.

    CAS  PubMed  Google Scholar 

  90. Goh XY, Rees JR, Paterson AL, et al. Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma. Gut. 2011;60:1317–26.

    Article  CAS  PubMed  Google Scholar 

  91. Agrawal N, Jiao Y, Bettegowda C, et al. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov. 2012;2:899–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Dulak AM, Schumacher SE, van Lieshout J, et al. Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res. 2012;72:4383–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Shah MA. Gastrointestinal cancer: targeted therapies in gastric cancer—the dawn of a new era. Nat Rev Clin Oncol. 2014;11:10–1.

    Article  CAS  PubMed  Google Scholar 

  94. Hanawa M, Suzuki S, Dobashi Y, et al. EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus. Int J Cancer. 2006;118:1173–80.

    Article  CAS  PubMed  Google Scholar 

  95. Kitagawa Y, Ueda M, Ando N, et al. Further evidence for prognostic significance of epidermal growth factor receptor gene amplification in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 1996;2:909–14.

    CAS  PubMed  Google Scholar 

  96. Wang KL, Wu TT, Choi IS, et al. Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Cancer. 2007;109:658–67.

    Article  CAS  PubMed  Google Scholar 

  97. Yu WW, Guo YM, Zhu M, et al. Clinicopathological and prognostic significance of EGFR over-expression in esophageal squamous cell carcinoma: a meta-analysis. Hepatogastroenterology. 2011;58:426–31.

    Article  CAS  PubMed  Google Scholar 

  98. Gonzaga IM, Soares-Lima SC, de Santos PT, et al. Alterations in epidermal growth factor receptors 1 and 2 in esophageal squamous cell carcinomas. BMC Cancer. 2012;12:569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. 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;24:1612–9.

    Article  CAS  PubMed  Google Scholar 

  100. Ferry DR, Anderson M, Beddard K, et al. A phase II study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. Clin Cancer Res. 2007;13:5869–75.

    Article  CAS  PubMed  Google Scholar 

  101. Rodriguez CP, Adelstein DJ, Rice TW, et al. A phase II study of perioperative concurrent chemotherapy, gefitinib, and hyperfractionated radiation followed by maintenance gefitinib in locoregionally advanced esophagus and gastroesophageal junction cancer. J Thorac Oncol. 2010;5:229–35.

    Article  PubMed  Google Scholar 

  102. Dragovich T, McCoy S, Fenoglio-Preiser CM, et al. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006;24:4922–7.

    Article  CAS  PubMed  Google Scholar 

  103. Dahan L, Chibaudel F, Di Fiore P, et al. Chemoradiation with FOLFOX plus cetuximab in locally advanced cardia or esophageal cancer: final results of a GERCOR phase II trial (ERaFOX). Paper presented at: 2011 American Society of Clinical Oncology annual meeting; 3–7 Jun 2011; Chicago.

    Google Scholar 

  104. Gavine PR, Mooney L, Kilgour E, et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012;72:2045–56.

    Article  CAS  PubMed  Google Scholar 

  105. Dahan L, Mariette C, Ychou M, et al. Neoadjuvant chemoradiotherapy with 5-fluorouracil-cisplatin combined with cetuximab in patients with resectable locally advanced esophageal carcinoma: a prospective phase I/II trial (FFCD-PRODIGE 3) – preliminary phase II results. Paper presented at: 2012 American Society of Clinical Oncology annual meeting; 1–5 Jun 2012; Chicago.

    Google Scholar 

  106. Crosby T, Hurt C, Falk S, et al. SCOPE 1: a phase II/III trial of chemoradiotherapy in esophageal cancer plus or minus cetuximab. Paper presented at: American Society of Clinical Oncology 2013 gastrointestinal cancers symposium; 24–26 Jan 2013; San Francisco.

    Google Scholar 

  107. Enzinger PC, Burtness B, Hollis D, et al. CALGB 80403/ECOG 1206: a randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. Paper presented at: 2010 ASCO annual meeting; 4–8 Jun 2010; Chicago. p. 74.

    Google Scholar 

  108. Gold PJ, Goldman B, Iqbal S, et al. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: A phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010;5:1472–6.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Tomblyn MB, Goldman BH, Thomas Jr CR, et al. Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-II study of the SWOG (S0414). J Thorac Oncol. 2012;7:906–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Reed CE, Decker PA, Schefter TE, et al. A phase II study of neoadjuvant therapy with cisplatin, docetaxel, panitumumab plus radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051). Paper presented at: 2012 American Society of Clinical Oncology annual meeting; 1–5 June 2012; Chicago.

    Google Scholar 

  111. Rüschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer: guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299–307.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Tafe LJ, Janjigian YY, Zaidinski M, et al. Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization. Arch Pathol Lab Med. 2010;135:1460–5.

    Article  CAS  Google Scholar 

  113. LoRusso PM, Weiss D, Guardino E, et al. Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer. Clin Cancer Res. 2011;17:6437–47.

    Article  CAS  PubMed  Google Scholar 

  114. Lynce F, Swain SM. Pertuzumab for the treatment of breast cancer. Cancer Invest. 2014;32:430–8.

    Article  CAS  PubMed  Google Scholar 

  115. Hecht JR, Bang YJ, Qin S, et al. Lapatinib in combination with capecitabine plus Oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC): the TRIO-013/LOGiC trial. J Clin Oncol. 2013;31(suppl 15s):243s. abstr LBA4001.

    Google Scholar 

  116. Satoh T, Xu RH, Chung HC, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN—a randomized, phase III study. J Clin Oncol. 2014;32:2039–49.

    Article  CAS  PubMed  Google Scholar 

  117. Shibuya M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J Biochem Mol Biol. 2006;39:469–78.

    Article  CAS  PubMed  Google Scholar 

  118. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-esophageal junction adenocarcinoma (REGARD): an international, randomized, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.

    Article  CAS  PubMed  Google Scholar 

  119. Wilke H, Muro K, Van Custem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-esophageal junction adenocarcinoma (RAINBOW): a double-blind randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.

    Article  CAS  PubMed  Google Scholar 

  120. Yoon HH, Bendell JC, Braiteh FS, et al. Ramucirumab (RAM) plus FOLFOX as front-line therapy (Rx) for advanced gastric or esophageal adenocarcinoma (GE-AC): randomized, double-blind, multicenter phase 2 trial. J Clin Oncol. 2014;32(suppl 15s):256s. abstr 4004.

    Google Scholar 

  121. Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.

    Article  CAS  PubMed  Google Scholar 

  122. Kang YK, Ohtsu A, Van Cutsem E, et al. AVAGAST: a randomized, double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC). J Clin Oncol. 2010;28(suppl):302s. abstr LBA4007.

    Google Scholar 

  123. Qin S. Phase III study of apatinib in advanced gastric cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2014;32(suppl 15s):255s. abstr 4003.

    Google Scholar 

  124. Knox JJ, Wong R, Darling GE, et al. Adjuvant sunitinib for locally advanced esophageal cancer: results of a phase II trial. Paper presented at: 2011 American Society of Clinical Oncology annual meeting; 3–7 June 2011; Chicago.

    Google Scholar 

  125. Ku GY, Janjigian YY, Shah MA, et al. Phase II trial of sorafenib in esophageal and gastroesophageal junction cancer: response and prolonged stable disease observed in adenocarcinoma. Paper presented at: American Society of Clinical Oncology 2013 gastrointestinal cancers symposium; 24–26 Jan 2013; San Francisco.

    Google Scholar 

  126. Ohigashi Y, Sho M, Yamada Y, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 2005;11:2947–53.

    Article  CAS  PubMed  Google Scholar 

  127. Lu B, Chen L, Liu L, et al. T-cell-mediated tumor immune surveillance and expression of B7 co-inhibitory molecules in cancers of the upper gastrointestinal tract. Immunol Res. 2011;50:269–75.

    Article  CAS  PubMed  Google Scholar 

  128. Kono K, Kawaida H, Takahashi A, et al. CD4(+)CD25 high regulatory T cells increase with tumor stage in patients with gastric and oesophageal cancers. Cancer Immunol Immunother. 2006;55:1064–71.

    Article  CAS  PubMed  Google Scholar 

  129. Fife BT, Pauken KE. The role of PD-1 pathway in autoimmunity and peripheral tolerance. Ann NY Acad Sci. 2011;1217:45–59.

    Article  CAS  PubMed  Google Scholar 

  130. Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.

    Article  CAS  PubMed  Google Scholar 

  131. Muro K, Bang Y, Shankaran V, et al. A phase 1b study of pembrolizumab (Pembro; MK-3475) in patients with advanced gastric cancer. Ann Oncol. 2014;25(abstr LBA15).

    Google Scholar 

  132. Graziano F, Galluccio N, Lorenzini P, et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol. 2011;29:4789–95.

    Article  CAS  PubMed  Google Scholar 

  133. Bachleitner-Hofmann T, Sun MY, Chen CT, et al. HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells. Mol Cancer Ther. 2008;7:3499–508.

    Article  CAS  PubMed  Google Scholar 

  134. Kato H, Arao T, Matsumoto K, et al. Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma. Int J Oncol. 2013;42:1151–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Yap TA, Harris D, Barriuso J, et al. Phase I trial to determine the dose range for the c-Met inhibitor ARQ 197 that inhibits c-Met and FAK phosphorylation, when administered by an oral twice-a-day schedule. Paper presented at: 2008 American Society of Clinical Oncology annual meeting; 30 May–3 Jun 2008; Chicago.

    Google Scholar 

  136. Matsumoto K, Arao T, Hamaguchi T, et al. FGFR2 gene amplification and clinicopathological features in gastric cancer. Br J Cancer. 2012;106:727–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Yashiro M, Shinto O, Nakamura K, et al. Synergistic antitumor effects of FGFR2 inhibitor with 5-fluorouracil on scirrhous gastric carcinoma. Int J Cancer. 2010;126:1004–16.

    CAS  PubMed  Google Scholar 

  138. Satoh T, Yamada Y, Muro K, et al. Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer. Cancer Chemother Pharmacol. 2012;69:439–46.

    Article  CAS  PubMed  Google Scholar 

  139. Enzinger PC, Ilson DH, Kelsen DP. Chemotherapy in esophageal cancer. Semin Oncol. 1999;26:12–20.

    CAS  PubMed  Google Scholar 

  140. Stahl M. Chemotherapy of esophageal carcinoma. Onkologie. 1999;22:98–104.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, American Hospital, Guzelbahce Sokak, No. 20, Tesvikiye, Istanbul, Turkey

    Sevil Bavbek MD

Authors
  1. Sevil Bavbek MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sevil Bavbek MD .

Editor information

Editors and Affiliations

  1. Department of Radiation Oncology, Hacettepe University, Faculty of Med., Ankara, Turkey

    Gokhan Ozyigit

  2. Department of Radiation Oncology, Koc University, Faculty of Medicine, Istanbul, Turkey

    Ugur Selek

  3. Department of Radiation Oncology, Baskent University School of Medicine, Adana, Turkey

    Erkan Topkan

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bavbek, S. (2016). Systemic Treatment of Esophageal Cancer. In: Ozyigit, G., Selek, U., Topkan, E. (eds) Principles and Practice of Radiotherapy Techniques in Thoracic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-28761-4_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-28761-4_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-28759-1

  • Online ISBN: 978-3-319-28761-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation