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A phase II trial of gefitinib for recurrent or metastatic cancer of the esophagus or gastroesophageal junction

  • PHASE II STUDIES
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Summary

Background Conventional chemotherapeutic agents are of limited benefit in patients with recurrent or metastatic cancer of the esophagus or gastroesophageal junction (GEJ). We report results from a phase II trial in this population using gefitinib, an oral epidermal growth factor receptor inhibitor. Patients and methods Eligibility required a diagnosis of esophageal or GEJ adenocarcinoma or squamous cell carcinoma, which was either metastatic or recurrent and incurable after initial therapy. No more than one prior chemotherapy regimen was permitted. Treatment consisted of gefitinib 250 mg daily for a minimum of 8 weeks. Results Between April 2003 and January 2010, 58 patients, including 18 who were chemotherapy-naïve, were entered into this trial. Toxicity was modest, although most experienced grade 1–2 diarrhea and/or skin rash. There were 4 partial responders (7%) and 10 patients with stable disease (17%). The clinical benefit (partial response and stable disease) lasted for a median 6.1 months. Median survival for all patients was 5.5 months with survival projections at 1-year of 24.6% and at 2-years of 12.5%. Conclusion Gefitinib was well tolerated but of limited efficacy in patients with recurrent or metastatic esophageal or GEJ cancer. Further study of this or similar agents will require better patient selection.

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References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  2. Enzinger PC, Mayer RJ (2003) Esophageal cancer. N Engl J Med 349:2241–2252

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  4. El-Rayes BF, Shields A, Zalupski M et al (2004) A phase II study of carboplatin and paclitaxel in esophagus cancer. Ann Oncol 15:960–965

    Article  CAS  PubMed  Google Scholar 

  5. Ajani JA, Moiseyenko VM, Tjulandin S et al (2007) Clinical benefit with doxetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal adenocarcinoma: the V-325 study group. J Clin Oncol 25:3205–3209

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Shah MA, Jhawer M, Ilson DH et al (2010) Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol 29:868–874

    Article  PubMed  Google Scholar 

  8. Wagner AD, Grothe W, Haerting J et al (2006) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24:2903–2909

    Article  CAS  PubMed  Google Scholar 

  9. Itakura Y, Sasano H, Shiga C et al (1994) Epidermal growth factor receptor overexpression in esophageal carcinoma. Cancer 74:795–804

    Article  CAS  PubMed  Google Scholar 

  10. Gibault L, Metges JP, Conan-Charlet V et al (2005) Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer. Br J Cancer 93:107–115

    Article  CAS  PubMed  Google Scholar 

  11. Wang KL, Wu TT, Choi IS et al (2007) Expression of epidermal growth factor receptor in esophagus and esophagogastric junction adenocarcinomas. Associations with poor outcome. Cancer 109:658–667

    Article  CAS  PubMed  Google Scholar 

  12. Ekman S, Bergqvist M, Heldin CH, Lennartsson J (2007) Activation of growth factor receptors in esophageal cancer—implications for therapy. Oncologist 12:1165–1177

    Article  CAS  PubMed  Google Scholar 

  13. Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  CAS  PubMed  Google Scholar 

  14. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  CAS  PubMed  Google Scholar 

  15. Kwak EL, Jankowski J, Thayer SP et al (2006) Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 12:4283–4287

    Article  CAS  PubMed  Google Scholar 

  16. Fukuoka M, Yano S, Giaccone G et al (2003) Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 21:2237–2246

    Article  CAS  PubMed  Google Scholar 

  17. Kris MG, Natale RB, Herbst RS et al (2003) Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer. JAMA 290:2149–2158

    Article  CAS  PubMed  Google Scholar 

  18. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  19. El-Maraghi RH, Eisenhauer EA (2008) Review of phase II trial designs used in studies of molecular targeted agents: outcomes and predictors of success in phase III. J Clin Oncol 26:1346–1354

    Article  PubMed  Google Scholar 

  20. Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160–1174

    Article  CAS  PubMed  Google Scholar 

  21. Kurata T, Matsuo K, Takada M et al (2006) Is the importance of achieving stable disease different between epidermal growth factor receptor tyrosine kinase inhibitors and cytotoxic agents in the second-line setting for advanced non-small cell lung cancer? J Thorac Oncol 1:684–691

    Article  PubMed  Google Scholar 

  22. Dragovich T, McCoy S, Fenoglio-Preiser CM et al (2006) Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol 24:4922–4927

    Article  CAS  PubMed  Google Scholar 

  23. Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA et al (2006) Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol 24:1612–1619

    Article  CAS  PubMed  Google Scholar 

  24. Ferry DR, Anderson M, Beddard K et al (2007) A phase II study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. Clin Cancer Res 13:5869–5875

    Article  CAS  PubMed  Google Scholar 

  25. Ilson DH, Kelsen D, Shah M et al (2011) A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. Cancer 117:1409–1414

    Article  CAS  PubMed  Google Scholar 

  26. Tew WP, Kelsen DP, Ilson DH (2005) Targeted therapies for esophageal cancer. Oncologist 10:590–601

    Article  CAS  PubMed  Google Scholar 

  27. Pinto C, Di Fabio F, Siena S et al (2007) Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 18:510–517

    Article  CAS  PubMed  Google Scholar 

  28. Javle M, Pande A, Iyer R et al (2008) Pilot study of gefitinib, oxaliplatin, and radiotherapy for esophageal adenocarcinoma. Tissue effect predicts clinical response. Am J Clin Oncol 31:329–334

    Article  CAS  PubMed  Google Scholar 

  29. Rodriguez CP, Adelstein DJ, Rice TW et al (2010) 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 5:229–235

    Article  PubMed  Google Scholar 

  30. Ruhstaller T, Pless M, Dietrich D et al (2011) Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II trial (SAKK 75/06). J Clin Oncol 29:626–631

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez CP, Adelstein DJ, Saxton JP et al (2009) Multiagent concurrent chemoradiotherapy (MACCRT) and gefitinib in locoregionally advanced head and neck squamous cell cancer (HNSCC). J Clin Oncol 27:310s (suppl; abstr 6037)

    Google Scholar 

  32. Kelly K, Chansky K, Gaspar LE et al (2008) Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol 26:2450–2456

    Article  CAS  PubMed  Google Scholar 

  33. Hofmann M, Stoss O, Shi D et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805

    Article  CAS  PubMed  Google Scholar 

  34. Bang YJ, Van Custem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet 376:687–697

    Article  CAS  PubMed  Google Scholar 

  35. Phillips BE, Tubbs RR, Rice TW et al (2011) Clinicopathologic features and treatment outcomes of patients (pts) with HER2-positive (pos) adenocarcinomas (ACA) of the esophagus (E) and gastroesophageal junction (GEJ). J Clin Oncol 29:65 (suppl. 4; abstr 71)

    Google Scholar 

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Funding

This work was supported by Astra-Zeneca Pharmaceuticals

Author information

Authors and Affiliations

  1. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    David J. Adelstein, Cristina P. Rodriguez & Denise I. Ives

  2. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    Lisa A. Rybicki

  3. Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA

    Thomas W. Rice

  4. Department of Solid Tumor Oncology, Taussig Cancer Institute, Desk R35, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    David J. Adelstein

Authors
  1. David J. Adelstein
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  2. Cristina P. Rodriguez
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  3. Lisa A. Rybicki
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  4. Denise I. Ives
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  5. Thomas W. Rice
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Corresponding author

Correspondence to David J. Adelstein.

Additional information

This trial was supported by Astra-Zeneca Pharmaceuticals

Clinicaltrials.gov ID: NCT00268346

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Adelstein, D.J., Rodriguez, C.P., Rybicki, L.A. et al. A phase II trial of gefitinib for recurrent or metastatic cancer of the esophagus or gastroesophageal junction. Invest New Drugs 30, 1684–1689 (2012). https://doi.org/10.1007/s10637-011-9736-z

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  • DOI: https://doi.org/10.1007/s10637-011-9736-z

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