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A Nationwide Retrospective Study of Perioperative Chemotherapy for Gastroesophageal Adenocarcinoma: Tolerability, Outcome, and Prognostic Factors

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Recent clinical trials have demonstrated the benefit and feasibility of perioperative chemotherapy for treatment of gastroesophageal adenocarcinoma (GEA). Despite convincing results, patients entering such trials usually represent only a fraction of those who are candidates for treatment. Confirmation of trial-reported effects and tolerability in unselected cohorts is therefore required. The aims of this study were to confirm the safety and efficacy of perioperative chemotherapy for resectable GEA and to delineate risks of treatment failure.

Methods

We conducted a national retrospective cohort analysis of patients admitted for perioperative chemotherapy for resectable GEA. Regimens were epirubicin and capecitabine combined with oxaliplatin or cisplatin.

Results

The intention-to-treat analysis included 271 patients. Eighty-seven percent of patients completed preoperative chemotherapy, and 63 % received radical resection. Age >70 years (odds ratio 2.58) and hypoalbuminemia (odds ratio 4.10) were independent predictors of not undergoing scheduled surgery (P = 0.033). Grade 3 or higher febrile neutropenia, fatigue, and diarrhea were common in the oxaliplatin group (n = 128), but hypomagnesaemia and tinnitus/hearing loss were more common in the cisplatin group (n = 135). The median overall survival was 26.4 months, and the 1- and 2-year survival rates were 76 and 53 %, respectively. Performance status >0 (hazard ratio 1.64) and elevated serum lactate dehydrogenase (hazard ratio 3.03) were independent predictors of poor prognosis (P ≤ 0.05).

Conclusions

Perioperative chemotherapy is feasible and well tolerated in patients with good performance status and low incidence of comorbidities.

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References

  1. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer. 1999;79:1522–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Portale G, Hagen JA, Peters JH, et al. Modern 5-year survival of resectable esophageal adenocarcinoma: single institution experience with 263 patients. J Am Coll Surg. 2006;202:588–96.

    Article  PubMed  Google Scholar 

  3. van ME, van der Gaast A, Tilanus HW, Poley JW, Muller K, van DH. Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: the Rotterdam experience. J Surg Oncol. 2009;100:32–7.

  4. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.

    Article  CAS  PubMed  Google Scholar 

  5. Briasoulis E, Liakakos T, Dova L, et al. Selecting a specific pre- or postoperative adjuvant therapy for individual patients with operable gastric cancer. Expert Rev Anticancer Ther. 2006;6:931–9.

    Article  PubMed  Google Scholar 

  6. Allum WH, Blazeby JM, Griffin SM, Cunningham D, Jankowski JA, Wong R. Guidelines for the management of oesophageal and gastric cancer. Gut. 2011;60:1449–72.

    Article  CAS  PubMed  Google Scholar 

  7. Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.

    Article  CAS  PubMed  Google Scholar 

  8. Haidich AB, Ioannidis JP. Patterns of patient enrollment in randomized controlled trials. J Clin Epidemiol. 2001;54:877–83.

    Article  CAS  PubMed  Google Scholar 

  9. Ford JG, Howerton MW, Lai GY, et al. Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review. Cancer. 2008;112:228–42.

    Article  PubMed  Google Scholar 

  10. Sobin LH, Compton CC. TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss; 2002.

    Google Scholar 

  11. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.

    Article  PubMed  Google Scholar 

  12. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

    Article  CAS  PubMed  Google Scholar 

  13. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.

    Article  CAS  PubMed  Google Scholar 

  14. Reece-Smith AM, Saha S, Cunnell ML, et al. MAGIC in practice: experience of peri-operative ECF/X chemotherapy in gastro-esophageal adenocarcinomas. J Surg Oncol. 2012;106:748–52.

    Article  CAS  PubMed  Google Scholar 

  15. Molina R, Lamarca A, Martinez-Amores B, et al. Perioperative chemotherapy for resectable gastroesophageal cancer: a single-center experience. Eur J Surg Oncol. 2013;39:814–22.

    Article  CAS  PubMed  Google Scholar 

  16. Starling N, Rao S, Cunningham D, et al. Thromboembolism in patients with advanced gastroesophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group. J Clin Oncol. 2009;27:3786–93.

    Article  CAS  PubMed  Google Scholar 

  17. Holmebakk T, Frykholm G, Viste A. Introducing national guidelines on perioperative chemotherapy for gastric cancer in Norway: a retrospective audit. Eur J Surg Oncol. 2010;36:610–6.

    Article  CAS  PubMed  Google Scholar 

  18. D’Ugo D, Rausei S, Biondi A, Persiani R. Preoperative treatment and surgery in gastric cancer: friends or foes? Lancet Oncol. 2009;10:191–5.

    Article  PubMed  Google Scholar 

  19. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.

    Article  PubMed  Google Scholar 

  20. Jensen LS, Nielsen H, Mortensen PB, Pilegaard HK, Johnsen SP. Enforcing centralization for gastric cancer in Denmark. Eur J Surg Oncol. 2010;36(Suppl 1):S50–4.

    Article  PubMed  Google Scholar 

  21. Dikken JL, Cats A, Verheij M, van de Velde CJ. Randomized trials and quality assurance in gastric cancer surgery. J Surg Oncol. 2013;107:298–305.

    Article  PubMed  Google Scholar 

  22. Ferri LE, Ades S, Alcindor T, et al. Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. Ann Oncol. 2012;23:1512–7.

    Article  CAS  PubMed  Google Scholar 

  23. Brell JM, Krishnamurthi SS, Javle M, et al. A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma. Cancer Chemother Pharmacol. 2009;63:851–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240:1052–61.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Caudle AS, Gonzalez-Angulo AM, Hunt KK, et al. Impact of progression during neoadjuvant chemotherapy on surgical management of breast cancer. Ann Surg Oncol. 2011;18:932–8.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Lordick F, Ott K, Krause BJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.

    Article  PubMed  Google Scholar 

  27. Messager M, Lefevre JH, Pichot-Delahaye V, Souadka A, Piessen G, Mariette C. The impact of perioperative chemotherapy on survival in patients with gastric signet ring cell adenocarcinoma: a multicenter comparative study. Ann Surg. 2011;254:684–93.

    Article  PubMed  Google Scholar 

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Acknowledgment

The authors wish to thank all the patients who participated in the study. We also thank Anne Østergaard Madsen and Anni Bahsen for logistical assistance. The authors thank the private foundation Blegdalens Erhvervs og Uddannelses Fond for a Grant covering data collection. The foundation had no influence on study design, data interpretation, or the writing of the article.

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The authors declare no conflict of interest.

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Correspondence to Anders Christian Larsen MD.

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Larsen, A.C., Holländer, C., Duval, L. et al. A Nationwide Retrospective Study of Perioperative Chemotherapy for Gastroesophageal Adenocarcinoma: Tolerability, Outcome, and Prognostic Factors. Ann Surg Oncol 22, 1540–1547 (2015). https://doi.org/10.1245/s10434-014-4127-2

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  • DOI: https://doi.org/10.1245/s10434-014-4127-2

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