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Multimodale Therapie des lokalisierten Magenkarzinoms

Multimodal therapy of localized gastric cancer

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Die lokalisierten Adenokarzinome des gastroösophagealen Übergangs und des Magens weisen nach alleiniger Operation mit einem Fünfjahresüberleben von ca. 25 % eine schlechte Prognose auf.

Ziel

Der Stellenwert der multimodalen Therapie und aktuelle Entwicklungen sollen vorgestellt werden.

Material und Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed und auf Präsentationen internationaler Kongresse (ASCO, ESMO) zur multimodalen Therapie.

Ergebnisse

Die multimodale Therapie der lokalisierten Adenokarzinome des Magens und des gastroösophagealen Übergangs ist von entscheidender Bedeutung für die Prognose des Patienten. Neben der standardisierten Chirurgie ist insbesondere das interdisziplinäre perioperative Therapiemanagement bei Patienten mit Tumoren ab klinischem Stadium T2 oder Lymphknotenbefall von hoher Relevanz. Die perioperative Chemotherapie sollte aktuell über insgesamt 8–9 Wochen prä- und ggf. weiteren 8–9 Wochen postoperativ durchgeführt werden. Diese sollte ein Fluoropyrimidin und ein Platinderivat (z. B. Cisplatin und 5‑FU − CF-Schema), gegebenenfalls auch als dritte Substanz Docetaxel (mit 5‑FU und Oxaliplatin − FLOT-Schema) beinhalten. Bei Tumoren des gastroösophagealen Übergangs kann alternativ zur perioperativen Chemotherapie auch eine neoadjuvante Radiochemotherapie, präferenziell mit einer Strahlentherapie bis 41,4 Gy in Kombination mit Carboplatin und Paclitaxel (CROSS-Schema) angewendet werden.

Schlussfolgerung

Die Integration von weiteren Medikamenten und die beste Kombination und Sequenz der verschiedenen Modalitäten (Chemotherapie und Strahlentherapie) ist Gegenstand aktueller Studien.

Abstract

Background

The prognosis of localized adenocarcinoma of the stomach and the gastroesophageal junction after surgery alone remains poor with a 5‑year overall survival rate of approximately 25 %.

Aim

The role of multimodal management and current developments are presented.

Material and methods

This study was based on a selective literature search in the PubMed database and presentations made at selected international meetings, e.g. the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) on multimodal treatment.

Results

The multimodal treatment of localized adenocarcinoma of the stomach and the gastroesophageal junction is of utmost importance for patient prognosis. Besides standardized surgery, perioperative management is particularly important in patients with a clinical T2 stage or higher or lymph node involvement. Perioperative chemotherapy, consisting of a neoadjuvant and a postoperative phase is the evidence-based standard approach in Europe, increasing the 5‑year overall survival rate by 13–14 %. Perioperative chemotherapy should be administered for 8–9 weeks preoperatively and if necessary for a further 8–9 weeks postoperatively. The chemotherapy regimen selected should include a fluoropyrimidine and a platinum derivative, e. g. the cisplatin and 5‑fluorouracil (5FU–CF) regimen. The addition of docetaxel (with 5FU and oxaliplatin–FLOT regimen) should be considered. For tumors of the gastroesophageal junction neoadjuvant radiochemotherapy can be applied instead of perioperative chemotherapy, preferably with radiotherapy up to 41.4 Gy in combination with carboplatin and paclitaxel (CROSS regimen).

Conclusion

The integration of modern therapeutic agents and the combination and sequence of the different modalities (e.g. chemotherapy and radiation) are currently being investigated in clinical trials.

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Literatur

  1. Cancer C, Fitzmaurice C, Dicker D et al (2015) Global burden of disease: the global burden of cancer 2013. JAMA Oncol 1:505–527

    Article  Google Scholar 

  2. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578

    Article  PubMed  Google Scholar 

  3. Holmes RS, Vaughan TL (2007) Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol 17:2–9

    Article  PubMed  Google Scholar 

  4. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ (2010) Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 11:439–449

    Article  PubMed  Google Scholar 

  5. Waddell T, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D (2013) Gastric cancer: ESMO–ESSO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24:vi57–63

    Article  PubMed  Google Scholar 

  6. Moehler M, Al-Batran SE, Andus T et al (2011) German S3-Guideline „Diagnosis and Treatment of Esophagogastric Cancer“. Z Gastroenterol 49:461–531

    Article  CAS  PubMed  Google Scholar 

  7. Porschen R, Buck A, Fischbach W et al (2015) S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus (Langversion 1,0 – September 2015, AWMF-Registernummer: 021/023OL). Z Gastroenterol 53:1288–1347

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Ychou M, Boige V, Pignon JP et al (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29:1715–1721

    Article  CAS  PubMed  Google Scholar 

  10. Schuhmacher C, Gretschel S, Lordick F et al (2010) Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: european Organisation for research and treatment of cancer randomized trial 40954. J Clin Oncol 28:5210–5218

    Article  PubMed  PubMed Central  Google Scholar 

  11. Alderson D, Langley RE, Nankivell MG (2015) Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072). J Clin Oncol 33:abstr 4002

    Google Scholar 

  12. Homann N, Pauligk C, Luley K et al (2012) Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5‑fluorouracil, oxaliplatin and docetaxel. Int J Cancer 130:1706–1713

    Article  CAS  PubMed  Google Scholar 

  13. Al-Batran SE, Hartmann JT, Hofheinz R et al (2008) 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 19:1882–1887

    Article  PubMed  Google Scholar 

  14. Pauligk C, Tannapfel A, Meiler J (2015) Pathological response to neoadjuvant 5‑FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5‑FU (ECF) in patients with locally advanced, resectable gastric/esophagogastric junction (EGJ) cancer: Data from the phase II part of the FLOT4 phase III study of the AIO. J Clin Oncol 33:abstr 4016

    Google Scholar 

  15. Messager M, Lefevre JH, Pichot-Delahaye V, Souadka A, Piessen G, Mariette C (2011) The impact of perioperative chemotherapy on survival in patients with gastric signet ring cell adenocarcinoma: a multicenter comparative study. Ann Surg 254:684–693

    Article  PubMed  Google Scholar 

  16. Heger U, Blank S, Wiecha C et al (2014) Is preoperative chemotherapy followed by surgery the appropriate treatment for signet ring cell containing adenocarcinomas of the esophagogastric junction and stomach? Ann Surg Oncol 21:1739–1748

    Article  PubMed  Google Scholar 

  17. Lorenzen S, Thuss-Patience P, Al-Batran SE et al (2013) Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol 24:2068–2073

    Article  CAS  PubMed  Google Scholar 

  18. Hofheinz R, Hegewisch-Becker S, HER-FLOT T‑PP (2014) Trastuzumab in combination with FLOT as perioperative treatment for patients with HER2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the AIO Gastric Cancer Study Group. J Clin Oncol 32(suppl):abstr 4073

    Google Scholar 

  19. Sjoquist KM, Burmeister BH, Smithers BM et al (2011) Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 12:681–692

    Article  PubMed  Google Scholar 

  20. Ronellenfitsch U, Schwarzbach M, Hofheinz R et al (2013) Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: Systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer 49(15):3149–3158

    Article  PubMed  Google Scholar 

  21. Shapiro J, van Lanschot JJ, Hulshof MC et al (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098

    Article  PubMed  Google Scholar 

  22. Stahl M, Walz MK, Stuschke M et al (2009) Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol 27:851–856

    Article  CAS  PubMed  Google Scholar 

  23. Burmeister BH, Thomas JM, Burmeister EA et al (2011) Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer 47:354–360

    Article  PubMed  Google Scholar 

  24. Paoletti X, Oba K, Burzykowski T et al (2010) Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA 303:1729–1737

    Article  CAS  PubMed  Google Scholar 

  25. Sasako M, Sakuramoto S, Katai H et al (2011) Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S‑1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol 29:4387–4393

    Article  CAS  PubMed  Google Scholar 

  26. Noh SH, Park SR, Yang HK et al (2014) Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5‑year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol 15:1389–1396

    Article  CAS  PubMed  Google Scholar 

  27. Bajetta E, Floriani I, Di Bartolomeo M et al (2014) Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5‑fluorouracil and folinic acid for radically resected gastric cancer. Ann Oncol 25:1373–1378

    Article  PubMed  Google Scholar 

  28. Smalley SR, Benedetti JK, Haller DG et al (2012) Updated analysis of SWOG-directed intergroup study 0116: A phase III trial of Adjuvant Radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol 30:2327–2333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fuchs CS, Tepper JE (2011) Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5‑FU (ECF) before and after CI 5‑FU and radiotherapy (CRT) compared with bolus 5‑FU/LV before and after CRT: Intergroup trial CALGB 80101. J Clin Oncol 29:abstr 4003

    Google Scholar 

  30. Norero E, Bustos M, Herrera ME et al (2016) Postoperative adjuvant treatment for gastric cancer improves long-term survival after curative resection and D2 lymphadenectomy. Results from a Latin American Center. Eur J Surg Oncol 42:94–102

    Article  CAS  PubMed  Google Scholar 

  31. Kim S, Lim DH, Lee J et al (2005) An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys 63:1279–1285

    Article  PubMed  Google Scholar 

  32. Park SH, Sohn TS, Lee J et al (2015) Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol 33:3130–3136

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum, Universitäres Cancer Center Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland

    A. Stein

  2. CUF Hospitals Cancer Centre, Lissabon, Portugal

    D. Arnold

  3. Krankenhaus Nordwest, Frankfurt a.M., Deutschland

    S. E. Al-Batran

Authors
  1. A. Stein
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  3. S. E. Al-Batran
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Correspondence to A. Stein.

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Interessenkonflikt

A. Stein: Forschungsunterstützung: Roche; Vortragshonorare: Roche, Lilly; Beratertätigkeit: Roche. D. Arnold: Forschungsunterstützung: Roche, Vortragshonorare und Beratertätigkeit: Roche, Lilly. S.E. Al-Batran: Forschungsunterstützung: Roche, Lilly, Vortragshonorare und Beratertätigkeit: Roche, Lilly, Nordic Pharma.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Stein, A., Arnold, D. & Al-Batran, S.E. Multimodale Therapie des lokalisierten Magenkarzinoms. Onkologe 22, 392–399 (2016). https://doi.org/10.1007/s00761-016-0031-7

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  • DOI: https://doi.org/10.1007/s00761-016-0031-7

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