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New developments in the treatment of esophageal cancer

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Abstract

Esophageal cancer is a rare but highly virulent malignancy in the United States and Western Europe, and adenocarcinoma of the esophagus has had the most rapid rate of increase of any solid tumor malignancy. Combined chemoradiotherapy is the standard of care in the nonsurgical management of esophageal cancer. Trials of preoperative chemotherapy followed by surgery have not shown a consistent benefit. Preoperative chemoradiotherapy followed by surgery continues to be actively studied in the surgical management of locally advanced esophageal cancer. Pathologic complete responses are seen in 20% to 40% of patients, with 5-year survival achieved in 30% to 35%. Newer agents, such as the taxanes and irinotecan, have been evaluated in combined chemoradiotherapy trials. These trials have shown promising antitumor activity and therapy tolerance, depending on the dose and schedule of therapy administered. Increasing the dose of radiotherapy, or adding a brachytherapy boost to chemoradiotherapy, has not improved the outcome of treatment in clinical trials. The advent of newer targeted therapies, including agents directed against growth factor receptor pathways, tumor angiogenesis, and tumor invasion and metastasis, is leading to a new generation of clinical trials combining these agents with conventional cytotoxic chemotherapy and radiation.

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References

  1. Jemal A, Thomas A, Murray T, Thun M:: Cancer statistics, 2002. CA J Clin 2002, 52:23–47.

    Google Scholar 

  2. Devesa SS, Blot WJ, Fraumeni JF Jr: Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998, 83:2049–2053.

    Article  PubMed  CAS  Google Scholar 

  3. Lagergren J, Bergstrom R, Lindgren A, et al.: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999, 340:825–831.

    Article  PubMed  CAS  Google Scholar 

  4. Earlam R, Cunha-Melo JR: Oesophogeal squamous cell carcinoma: II. A critical view of radiotherapy. Br J Surg 1980, 67:457–461.

    Article  PubMed  CAS  Google Scholar 

  5. Muller JM, Erasmi H, Stelzner M, et al.: Surgical therapy of oesophageal carcinoma. Br J Surg 1990, 77:845–857.

    Article  PubMed  CAS  Google Scholar 

  6. Kelsen DP, Ginsberg R, Pajak TF, et al.: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 1998, 339:1979–1984.

    Article  PubMed  CAS  Google Scholar 

  7. Clark P: Surgical resection with or without pre-operative chemotherapy in oesophageal cancer: an updated analysis of a randomized controlled trial conducted by the UK Medical Research Council Upper GI Tract Cancer Group [abstract]. Proc ASCO 2001, 20:502. Two cycles of preoperative chemotherapy with 5-FU and cisplatin followed by surgery improved patient survival, compared with surgery alone. The results of this trial differed from those from the American Intergroup trial, which failed to show a benefit for the addition of five cycles of pre- and postoperative 5-FU and cisplatin, compared with surgery alone.

    Google Scholar 

  8. Herskovic A, Martz LK, Al-Sarraf M, et al.: Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992, 326:1593–1598.

    Article  PubMed  CAS  Google Scholar 

  9. Leichman L, Herskovic A, Leichman CG, et al.: Preooperative therapy for squamous-cell cancer of the esophagus. J Clin Oncol 1987, 5:365–370.

    PubMed  CAS  Google Scholar 

  10. Forastiere AA, Orringer MB, Perez-Tamayo C, et al.: Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: final report. J Clin Oncol 1993, 11:1118–1123.

    PubMed  CAS  Google Scholar 

  11. Walsh TN, Noonan N, Hollywood D, et al.: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996, 335:462–467.

    Article  PubMed  CAS  Google Scholar 

  12. Bosset JF, Gignoux M, Triboulet JP, et al.: Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 1997, 337:161–167.

    Article  PubMed  CAS  Google Scholar 

  13. Urba SG, Orringer MB, Turrisi A: Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001, 19:305–313.

    PubMed  CAS  Google Scholar 

  14. Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001, 345:725–730. Postoperative treatment with 5-FU, leucovorin, and radiotherapy after resection of gastric or gastroesophageal cancer improved survival compared with surgery alone. This trial established the new standard of care in gastric cancer management, postoperative chemotherapy and radiotherapy.

    Article  PubMed  CAS  Google Scholar 

  15. Coia LR, Minsky BD, Berkey BA, et al.: Outcome of patients receiving radiation for cancer of the esophagus: results of the 1992–1994 Patterns Care Study. J Clin Oncol 2001, 8:455–462. In evaluation of community-based treatment of locally advanced esophageal cancer, the superiority of combined chemoradiotherapy was confirmed compared with radiotherapy alone in clinical practice. A trend toward improved survival was observed in patients undergoing esophagectomy after chemoradiotherapy, compared with chemoradiotherapy alone.

    Google Scholar 

  16. Cooper JS, Guo MD, Herskovic A, et al.: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA 1999, 281:1623–1627.

    Article  PubMed  CAS  Google Scholar 

  17. Minsky BD, Neuberg D, Kelsen DP, et al.: Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 1999, 43:517–523.

    Article  PubMed  CAS  Google Scholar 

  18. Minsky BD, Berkey B, Kelsen DK, et al.: Preliminary results of intergroup INT 0123 randomized trial of combined modality therapy (CMT) for esophageal cancer: standard vs. high dose radiation therapy [abstract]. Proc ASCO 2000, 19:239. Intergroup trial 0123 compared 6400 cGy of radiotherapy with a conventional dose, 5040 cGy, combined with concurrent 5-FU and cisplatin in locally advanced esophageal cancer, treated nonsurgically. There was no benefit with the higher dose of radiotherapy.

    Google Scholar 

  19. Gaspar LE, Winter K, Kocha WI, et al.: A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group study 9207): final report. Cancer 2000, 88:988–995. RTOG trial 9207 evaluated the addition of a brachytherapy boost to combined cisplatin, 5-FU, and radiotherapy in locally advanced esophageal cancer. No improvement in local tumor control was observed, and the added morbidity was substantial.

    Article  PubMed  CAS  Google Scholar 

  20. Ilson D, Arquette M, Costa F, et al.: Preoperative paclitaxel/ cisplatin in esophageal carcinoma: a phase II multicenter trial [abstract]. Proc ASCO 1997, 16:926.

    Google Scholar 

  21. Bains M, Stojadinovic A, Minsky B, et al.: A phase II trial of preoperative combined modality therapy for localized esophageal carcinoma: initial results. J Thorac Cardiovasc Surg 2002, in press.

  22. Heath EI, Burtness BA, Heitmiller R, et al.: Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus. J Clin Oncol 2000, 18:868–876.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  24. Bleiberg H, Conroy T, Paillot B, et al.: Randomized phase II study of cisplatin and 5-FU versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer 1997, 33:1216–1220.

    Article  PubMed  CAS  Google Scholar 

  25. Webb A, Cunningham D, Scarffe JH, et al.: A randomised trial comparing ECF with FAMTX in advanced oesophago-gastric cancer. J Clin Oncol 1997, 15:261–267.

    PubMed  CAS  Google Scholar 

  26. Vanhoefer U, Rougier P, Wilke H, et al.: Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol 2000, 18:2648–2657. In a trial in gastric and gastroesophageal junction cancer, a comparative evaluation of cisplatin and 5-FU with the ELF or FAMTX regimen showed marginal activity and no superiority for any of the regimens. All regimens had substantial toxicity and led to median survival duration of less than 8 months. The trial results raised questions about the adoption of 5-FU and cisplatin as the standard of care in gastric and gastroesophageal cancer.

    PubMed  CAS  Google Scholar 

  27. Ajani J, Ilson D, Daugherty K, et al.: Activity of Taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst 1994, 86:1086–1091.

    Article  PubMed  CAS  Google Scholar 

  28. Kelsen DP, Ilson D, Wadleigh R, et al.: A phase II multi-center trial of paclitaxel as a weekly one-hour infusion in advanced esophageal cancer [abstract]. Proc ASCO 2000, 19:1266.

    Google Scholar 

  29. Einzig AI, Neuberg D, Remick SC, et al.: Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293. Med Oncol 1996, 13:87–93.

    Article  PubMed  CAS  Google Scholar 

  30. Ilson DH, Ajani J, Bhalla K, et al.: Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. J Clin Oncol 1998, 16:1826–1834.

    PubMed  CAS  Google Scholar 

  31. Garcia-Alfonso P, Guevara S, Lopez P, et al.: Taxol and cisplatin + 5-fluorouracil sequential in advanced esophageal cancer [abstract]. Proc ASCO 1998, 17:998.

    Google Scholar 

  32. Ilson DH, Forastiere A, Arquette M, et al.: A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus. Cancer J 2000, 6:316–323.

    PubMed  CAS  Google Scholar 

  33. Petrasch S, Welt A, Reinacher A, et al.: Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. Br J Cancer 1998, 78:511–514.

    PubMed  CAS  Google Scholar 

  34. van der Gaast A, Kok TC, Kerkhofs L, et al.: Phase I study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced oesophageal cancer. Br J Cancer 1999, 80:1052–1057.

    Article  PubMed  Google Scholar 

  35. Philip PS, Gadgeel M, Hussain M, et al.: Phase II study of paclitaxel and carboplatin in patients with advanced gastric and esophageal cancers [abstract]. Proc ASCO 1998, 17:1001.

    Google Scholar 

  36. Adelstein DJ, Rice TW, Rybicki LA, et al.: Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer? A nonrandomized comparison with fluorouracil-based therapy. J Clin Oncol 2000, 18:2032–2039.

    PubMed  CAS  Google Scholar 

  37. Blanke CD, Choy H, Teng M, et al.: Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer. Semin Radiat Oncol 1999, 9:43–52.

    PubMed  CAS  Google Scholar 

  38. Urba S, Orringer M, Iannettoni M, et al.: A phase II trial of preoperative cisplatin, paclitaxel, and radiation therapy (XRT) before trans-hiatal esophagectomy (THE) in patients (PTS) with loco-regional esophageal cancer (CA) [abstract]. Proc ASCO 2000, 19:960.

    Google Scholar 

  39. Wright CD, Wain JC, Lynch TJ, et al.: Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study. J Thorac Cardiovasc Surg 1997, 114:811–815.

    Article  PubMed  CAS  Google Scholar 

  40. Meluch AA, Hainsworth JD, Gray JR, et al.: Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial. Cancer J Sci Am 1999, 5:84–91.

    PubMed  CAS  Google Scholar 

  41. Kelsen D, Ilson D, Lipton L, et al.: A phase I trial of radiation therapy plus concurrent fixed dose cisplatin with escalating doses of paclitaxel as a 96 hour continuous infusion in patients with localized esophageal cancer [abstract]. Proc ASCO 1999, 18:1039.

    Google Scholar 

  42. Safran H, Gaissert H, Akerman P, et al.: Paclitaxel, cisplatin, and concurrent radiation for esophageal cancer. Cancer Invest 2001, 19:1–7.

    Article  PubMed  CAS  Google Scholar 

  43. Ajani JA, Komaki R, Walsh GL, et al.: CPT-11 plus cisplatin as induction chemotherapy followed by chemoradiotherapy in resectable carcinoma of the esophagus and GE junction [abstract]. Proc ASCO 2001, 20:521.

    Google Scholar 

  44. Mauer AM, Haraf DC, Ferguson MK, et al.: Docetaxel-based combined modality therapy for locally advanced carcinoma of the esophagus and gastric cardia [abstract]. Proc ASCO 2000, 19:954.

    Google Scholar 

  45. Enzinger PC, Kulke MH, Clark JW, et al.: Phase II trial of CPT-11 in previously untreated patients with advanced adenocarcinoma of the esophagus and stomach [abstract]. Proc ASCO 2000, 19:1243.

    Google Scholar 

  46. Li-Shin Lin L, Hecht JR: A phase II trial of irinotecan in patients with advanced adenocarcinoma of the gastroesophageal (GE) junction [abstract]. Proc ASCO 2000, 19:1130.

    Google Scholar 

  47. Blanke CD, Haller DG, Benson Blanke AB, et al.: Multicenter phase II study of CPT-11, 5-fluorouracil, and leucovorin in patients with previously untreated adenocarcinoma of the stomach or GE junction [abstract]. Proc ASCO 2000, 19:1141.

    Google Scholar 

  48. Findlay MPN, Ackland S, Gebski V, et al.: Phase II study of irinotecan, leucovorin and 5FU (ILF) in advanced gastric cancer [abstract]. Proc ASCO 2001, 20:1655.

    Google Scholar 

  49. Ilson D, Saltz L, Enzinger P, et al.: A phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 1999, 17:3270–3275.

    PubMed  CAS  Google Scholar 

  50. Ajani JA, Fairweather J, Pisters PW, et al.: Phase II study of CPT-11 plus cisplatin in patients with advanced gastric and GE junction carcinomas [abstract]. Proc ASCO 1999, 18:927.

    Google Scholar 

  51. Gold PJ, Carter G, Livingston R: Phase II trial of irinotecan and mitomycin C in the treatment of metastatic esophageal and gastric cancers [abstract]. Proc ASCO 2001, 20:644.

    Google Scholar 

  52. Pozzo C, Bugat R, Peschel C: Irinotecan in combination with CDDP or 5-FU and folinic acid is active in patients with advanced gastric or gastrooesophageal junction adenocarcinoma: final results of a randomised phase II study [abstract]. Proc ASCO 2001, 20:531.

    Google Scholar 

  53. Anderson S, Ilson D, Bains M, et al.: Phase I trial of cisplatin and escalating dose irinotecan given weekly with concurrent radiation in locally advanced esophageal cancer [abstract]. Proc ASCO 2001, 20:629.

    Google Scholar 

  54. Metzger R, Leichman CG, Danenberg KD, et al.: ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 1998, 16:309–316.

    PubMed  CAS  Google Scholar 

  55. Raben D, Helfrich B, Chan D, et al.: Anti-EGFR antibody potentiates radiation (RT) and chemotherapy (CT) cytotoxicity in human non-small cell lung cancer (NSCLC) cells in vitro and in vivo [abstract]. Proc ASCO 2001, 20:1026.

    Google Scholar 

  56. Saltz L, Rubin M, Hochster H, et al.: Cetuximab plus irinotecan is active in CPT-11-refractory colorectal cancer that expresses epidermal growth factor receptor [abstract]. Proc ASCO 2001, 20:7.

    Google Scholar 

  57. Perez-Soler R, Chachoua A, Huberman M, et al.: A phase II trial of the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774, following platinum-based chemotherapy, in patients with advanced, EGFR-expressing, non-small cell lung cancer [abstract]. Proc ASCO 2001, 20:1235.

    Google Scholar 

  58. Senzer NN, Soulieres D, Siu L, et al.: Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced squamous cell carcinoma of the head and neck [abstract]. Proc ASCO 2001, 20:6.

    Google Scholar 

  59. Mandel DB, Schreck RE, West DC, et al.: The angiogenesis inhibitor SU5416 has long-lasting effects on vascular endothelial growth factor receptor phosphorylation and function. Clin Cancer Res 2000, 6:4848–4858.

    Google Scholar 

  60. Downey RJ, Ilson D, Koong H, et al.: 8FDG PET measures the pathologic response of esophageal cancer to induction therapy [abstract]. Proc ASCO 2001, 20:503.

    Google Scholar 

  61. Flamen P, Van Cutsem E, Lerut L, et al.: The utility of positron emission tomography with 18F-fluorodeoxyglucose to predict the pathologic response and survival of esophageal cancer after preoperative chemoradiation therapy [abstract]. Proc ASCO 2001, 20:504.

    Google Scholar 

  62. Weber WA, Ott K, Becker K, et al.: Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 2001, 19:3058–3066.

    PubMed  CAS  Google Scholar 

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Ilson, D.H. New developments in the treatment of esophageal cancer. Curr Oncol Rep 4, 213–221 (2002). https://doi.org/10.1007/s11912-002-0018-y

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