Systemtherapie des Ösophaguskarzinoms

Neben der histologischen Unterscheidung zwischen Plattenepithel- und Adenokarzinom sind Lokalisation und Lagebeziehung des Tumors wesentlicher Bestandteil für die Planung von Diagnostik und Therapie des Ösophaguskarzinoms. Durch multimodale Therapiekonzepte konnte die Prognose für beide Tumorentitäten verbessert werden. Dieser Beitrag konzentriert sich auf die aktuellen Empfehlungen und Entwicklungen in der kurativen und palliativen Systemtherapie.

^* Diese Autoren haben gleichermaßen zu dieser Arbeit beigetragen.

Publikationsverlauf

Artikel online veröffentlicht:
02. November 2020

• Literatur

• 1 Robert-Koch-Institut, Zentrum für Krebsregisterdaten (ZfKD) 2019. Krebs in Deutschland 2015/2016. https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/krebs_in_deutschland_node.html
• 2 Coupland VH, Lagergren J, Luchtenborg M. et al. Hospital volume, proportion resected and mortality from oesophageal and gastric cancer: a population-based study in England, 2004–2008. Gut 2013; 62: 961-966
• 3 Thuss-Patience P, Vecchione L, Keilholz U. Should cT2 esophageal cancer get neoadjuvant treatment before surgery?. J Thorac Dis 2017; 9: 2819-2823
• 4 Al-Batran SE, Homann N, Pauligk C. et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019; 393: 1948-1957
• 5 Mariette C, Dahan L, Mornex F. et al. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol 2014; 32: 2416-2422
• 6 Shapiro J, van Lanschot JJB, Hulshof M. et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16: 1090-1098
• 7 van Hagen P, Hulshof MC, van Lanschot JJ. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084
• 8 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
• 9 Hoeppner J, Lordick F, Brunner T. et al. ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus. BMC Cancer 2016; 16: 503
• 10 Leong T, Smithers BM, Haustermans K. et al. TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol 2017; 24: 2252-2258
• 11 Bedenne L, Michel P, Bouche O. et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007; 25: 1160-1168
• 12 Minsky BD, Pajak TF, Ginsberg RJ. et al. Radiation Therapy Oncology Group phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 2002; 20: 1167-1174
• 13 Hulshof MCCM, Geijsen D, Rozema T. et al. A randomized controlled phase III multicenter study on dose escalation in definitive chemoradiation for patients with locally advanced esophageal cancer: ARTDECO study. J Clin Oncol 2020; 38 (Suppl. 04) 281-281
• 14 BMS 2020. Press release, CheckMate-577. https://news.bms.com/press-release/corporatefinancial-news/checkmate-577-phase-3-trial-evaluating-opdivo-nivolumab-adjuva
• 15 Kelly RJ, Lockhart AC, Jonker DJ. et al. CheckMate 577: A randomized, double-blind, phase 3 study of nivolumab (Nivo) or placebo in patients (Pts) with resected lower esophageal (E) or gastroesophageal junction (GEJ) cancer. J Clin Oncol 2017; 35 (Suppl. 04) TPS212-TPS212
• 16 Moehler M, Al-Batran SE, Andus T. et al. S3-Leitlinie Magenkarzinom – Diagnostik und Therapie der Adenokarzinome des Magens und des ösophagogastralen Übergangs – Langversion 2.0. AWMF-Registernummer: 032/009OL. Z Gastroenterol 2019; 57: 1517-1632
• 17 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: 4991-4997
• 18 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: 1435-1442
• 19 Dank M, Zaluski J, Barone C. et al. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 2008; 19: 1450-1457
• 20 Guimbaud R, Louvet C, Ries P. et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Federation Francophone de Cancerologie Digestive, Federation Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol 2014; 32: 3520-3526
• 21 Bang YJ, Van Cutsem E, Feyereislova A. et al. 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, randomised controlled trial. Lancet 2010; 376: 687-697
• 22 Al-Batran SE, Moorahrend E, Maintz C. et al. Clinical Practice Observation of Trastuzumab in Patients with Human Epidermal Growth Receptor 2-Positive Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. Oncologist 2020; 25: e1181-e1187
• 23 Thuss-Patience PC, Kretzschmar A, Bichev D. et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer – a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011; 47: 2306-2314
• 24 Fuchs CS, Tomasek J, Yong CJ. et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014; 383: 31-39
• 25 Wilke H, Muro K, van Cutsem E. et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014; 15: 1224-1235
• 26 Shitara K, Doi T, Dvorkin M. et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018; 19: 1437-1448
• 27 Tabernero J, van Cutsem E, Bang YJ. et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. J Clin Oncol 2019; 37 (Suppl. 18) LBA4007-LBA4007
• 28 BMS 2020. Press release, CheckMate-649. https://news.bms.com/press-release/corporatefinancial-news/checkmate-649-phase-3-trial-evaluating-opdivo-nivolumab-plus-c
• 29 Shitara K, Ozguroglu M, Bang YJ. et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 2018; 392: 123-133
• 30 Kang YK, Boku N, Satoh T. et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390: 2461-2471
• 31 Fuchs CS, Doi T, Jang RW. et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol 2018; 4: e180013
• 32 Rodriquenz MG, Roviello G, D’Angelo A. et al. MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link With Novel Immunotherapy. J Clin Med 2020; 9: 1427
• 33 Bleiberg H, Conroy T, Paillot B. et al. Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer 1997; 33 (08) 1216-1220
• 34 Moehler M, Maderer A, Thuss-Patience PC. et al. Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Ann Oncol 2020; 31: 228-235
• 35 Albertsson M, Johansson B, Friesland S. et al. Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer. Med Oncol 2007; 24: 407-412
• 36 Ilson DH, Wadleigh RG, Leichman LP. et al. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol 2007; 18: 898-902
• 37 Metges J, François E, Shah M. et al. The phase 3 KEYNOTE-181 study: pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer. Ann Oncol 2019; 30: iv130
• 38 Kato K, Cho BC, Takahashi M. et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2019; 20: 1506-1517
• 39 MSD 2020. Press release KEYNOTE-590. https://www.merck.com/news/mercks-keytruda-pembrolizumab-in-combination-with-chemotherapy-significantly-improved-overall-survival-and-progression-free-survival-compared-with-chemotherapy-in-locally-advanced-or/