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Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Gastrointestinal Oncology

Influence of Different Neoadjuvant Chemotherapy Regimens on Response, Prognosis, and Complication Rate in Patients with Esophagogastric Adenocarcinoma

Authors: Christoph Springfeld, MD, PhD, Christiane Wiecha, Romy Kunzmann, Ulrike Heger, MD, Wilko Weichert, MD, Rupert Langer, MD, Annika Stange, MD, Susanne Blank, MD, Leila Sisic, MD, Thomas Schmidt, MD, PhD, Florian Lordick, MD, Dirk Jäger, MD, Lars Grenacher, MD, Tom Bruckner, PhD, Markus W. Büchler, MD, Katja Ott, MD

Published in: Annals of Surgical Oncology | Special Issue 3/2015

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Abstract

Background

Perioperative chemotherapy improves survival in patients with advanced esophagogastric cancer, but the optimal treatment regimen remains unclear. More intensive chemotherapy may improve outcome, but also increase toxicity and complications.

Methods

A total of 843 patients were included in this retrospective study and stratified in 4 groups: doublet therapy with cisplatin or oxaliplatin and 5-fluorouracil (groups A/B) or triplet therapy with additional epirubicin or taxane (groups C/D). The influence of the different neoadjuvant chemotherapy regimens on response, prognosis, and complications was assessed.

Results

Clinical and pathological response were associated with longer overall survival (OS; p < 0.001). No significant differences regarding response or OS were found, but there was a trend toward better outcome in group D (taxane-containing triplet). In the subgroup of 669 patients with adenocarcinomas of the esophagogastric junction (AEG), patients who had received taxane-containing regimens had a significantly longer OS (p = 0.037), but taxane use was not an independent factor in multivariate analysis. Triple therapy with taxanes did not result in a higher complication rate or postoperative mortality.

Conclusions

Although no superior neoadjuvant chemotherapy regimen was identified for patients with esophagogastric adenocarcinoma, taxane-containing regimens should be further investigated in randomized trials, especially in patients with AEG tumors.

Literature
  1. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet. 2009;374:477–90.PubMedPubMed CentralView Article
  2. Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381:400–12.PubMedView Article
  3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.PubMedView Article
  4. Wilke H, Lordick F, Meyer HJ, Stahl M. (Neo)-adjuvant chemo(-radio) therapy for adenocarcinomas of the gastroesophageal junction and the stomach in the West. Dig Surg. 2013;30:112–8.PubMedView Article
  5. Sehdev A, Catenacci DV. Perioperative therapy for locally advanced gastroesophageal cancer: current controversies and consensus of care. J Hematol Oncol. 2013;6:66.PubMedPubMed CentralView Article
  6. Okines A, Verheij M, Allum W, Cunningham D, Cervantes A. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v50–v54.PubMedView Article
  7. Lutz MP, Zalcberg JR, Ducreux M, et al. Highlights of the EORTC St. Gallen International Expert Consensus on the primary therapy of gastric, gastroesophageal and oesophageal cancer—differential treatment strategies for subtypes of early gastroesophageal cancer. Eur J Cancer. 2012;48:2941–53.PubMedView Article
  8. Ajani JA, Bentrem DJ, Besh S, et al. Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw. 2013;11:531–46.
  9. 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.PubMedView Article
  10. 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.PubMedView Article
  11. 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.PubMedView Article
  12. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.PubMedView Article
  13. Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, Haerting J, Fleig WE. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;3:CD004064.PubMed
  14. 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.PubMedView Article
  15. Al-Batran SE, Hartmann JT, Hofheinz R, et al. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008;19:1882–7.PubMedView Article
  16. 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.PubMedView Article
  17. Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640–7.PubMedView Article
  18. Heger U, Bader F, Lordick F, et al. Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis. Gastric Cancer. 2014;17:478–88.PubMedView Article
  19. Ott K, Sendler A, Becker K, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6:159–67.PubMedView Article
  20. 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.PubMedView Article
  21. 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.PubMedView Article
  22. Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.PubMedView Article
  23. Bader FG, Lordick F, Fink U, et al. Paclitaxel in the neoadjuvant treatment for adeno carcinoma of the distal esophagus (AEG I). A comparison of two phase II trials with long-term follow-up. Onkologie. 2008;3:366–72.View Article
  24. Becker K, Mueller JD, Schuhmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98:1521–30.PubMedView Article
  25. Fields RC, Strong VE, Gonen M, et al. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer. 2011;104:1840–7.PubMedPubMed CentralView Article
  26. Ott K, Blank S, Becker K, et al. Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor. Langenbecks Arch Surg. 2013;398:239–49.PubMedView Article
  27. Vallböhmer H, Hölscher AH, DeMeester S, et al. A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer. Ann Surg. 2010;252:744–9.PubMedView Article
  28. Schuhmacher C, Reim D, Novotny A. Neoadjuvant treatment for gastric cancer. J Gastric Cancer. 2013;13:73–8.PubMedPubMed CentralView Article
  29. Fink U, Schuhmacher C, Stein HJ, et al. Preoperative chemotherapy for stage III–IV gastric carcinoma: feasibility, response and outcome after complete resection. Br J Surg. 1995; 82:1248–52.PubMedView Article
  30. Schuhmacher CP, Fink U, Becker K, Busch R, Dittler HJ, Mueller J, Siewert JR. Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer. 2001;91:918–27.PubMedView Article
  31. Lorenzen S, Blank S, Lordick F, Siewert JR, Ott K. Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. Ann Surg Oncol. 2012;19:2119–27.PubMedView Article
  32. Reim D, Gertler R, Novotny A, et al. Adenocarcinomas of the esophagogastric junction are more likely to respond to preoperative chemotherapy than distal gastric cancer. Ann Surg Oncol. 2012;19:2108–18.PubMedView Article
  33. Ronellenfitsch U, Schwarzbach M, Hofheinz R, et al. Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer. 2013;49:3149–58.PubMedView Article
  34. Becker K, Langer R, Reim D, et al. Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases. Ann Surg. 2011;253:934–9.PubMedView Article
  35. Lowy AM, Mansfield PF, Leach SD, Pazdur R, Dumas P, Ajani JA. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999;229:303–8.PubMedPubMed CentralView Article
  36. Lorenzen S, Thuss-Patience P, Al-Batran SE, et al. Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol. 2013;24:2068–73.PubMedView Article
  37. Langer R, Ott K, Feith M, Lordick F, Siewert JR, Becker K. Prognostic significance of histopathological tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. Mod Pathol. 2009;22:1555–63.PubMedView Article
  38. Homann N, Pauligk C, Luley K, et al. Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel. Int J Cancer. 2012;130:1706–13.PubMedView Article
  39. Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210–8.PubMedPubMed CentralView Article
Metadata
Title
Influence of Different Neoadjuvant Chemotherapy Regimens on Response, Prognosis, and Complication Rate in Patients with Esophagogastric Adenocarcinoma
Authors
Christoph Springfeld, MD, PhD
Christiane Wiecha
Romy Kunzmann
Ulrike Heger, MD
Wilko Weichert, MD
Rupert Langer, MD
Annika Stange, MD
Susanne Blank, MD
Leila Sisic, MD
Thomas Schmidt, MD, PhD
Florian Lordick, MD
Dirk Jäger, MD
Lars Grenacher, MD
Tom Bruckner, PhD
Markus W. Büchler, MD
Katja Ott, MD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4617-x

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