Download PDF
Der Klinikarzt 2008; 37(7/08): 366-371
DOI: 10.1055/s-0028-1083742
In diesem Monat

© Georg Thieme Verlag Stuttgart · New York

Nichtchirurgische Therapie des Magenkarzinoms – Neue Strategien und neue Medikamente

Non chirurgic therapy of gastric cancer – New treatment strategies and new drugsKerstin Schütte1 , Peter Malfertheiner1
  • 1Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto–von–Guericke–Universität Marburg(Direktor: Prof. Dr. Dr. h.c. P. Malfertheiner)
Further Information

Publication History

Publication Date:
31 July 2008 (online)

Also available at
    Permissions and Reprints

Während ein lokal begrenzter Tumor durch eine chirurgische Therapie oder – in ausgewählten Fällen – durch eine endoskopische Mukosaresektion optimal behandelt werden kann, liegt bei den meisten Patienten entweder wegen eines lokal fortgeschrittenen Tumors oder wegen Fernmetastasen ein Erkrankungsstadium vor, in dem eine kurative Resektion nicht möglich ist. Dann ist neben palliativen chirurgischen oder endoskopischen Maßnahmen eine systemische palliative Chemotherapie häufig die einzige Behandlungsoption. Basierend auf den Ergebnissen zweier großer europäischer Studien gilt die perioperative Chemotherapie mit dem Ziel der besseren lokalen Tumorkontrolle und der Therapie noch okkulter Fernmetastasen in Europa heute als Standard. Während in der palliativen Situation bisher die Kombinationstherapie mit Cisplatin und 5–Fluorouracil als Referenztherapie etabliert war, ist das Spektrum der möglichen Therapieoptionen heute deutlich größer. Oxaliplatin und Capecitabin sowie taxan– und irinotecanhaltige Schemata haben sich bei der Therapie des fortgeschrittenen Magenkarzinoms als wirksam erwiesen. Die zusätzliche Behandlung mit Inhibitoren der EGFR– und VEGF–Signalwege zeigt bislang in einarmigen Phase–II–Studien vielversprechende Ergebnisse, sollte aber außerhalb von Studien nicht zum Einsatz kommen. Nicht zuletzt bleibt aber eine optimale supportive Therapie von entscheidender Bedeutung.

In contrast to limited tumors that can be treated by surgical resection or – in well selected cases – by endoscopic mucosectomy, most of the patients with gastric cancer present either locally advanced stage or metastatic disease making curative resection impossible. In these cases, a systemic palliative chemotherapy is often the only available option for treatment besides palliative surgical or endoscopic techniques. Based on results of two large–scale European studies, a perioperative chemotherapy is considered as standard in Europe with respect to the aim of improved local tumor–control and therapy of occult distant metastases. So far the use of combined therapy with cisplatin and 5–FU was established as reference therapy, but the scale of palliative therapeutic options has been widened recently. Oxaliplatin and capecitabine as well as taxanes and irinotecan have been shown to be effective in the treatment of advanced gastric cancer. An additional therapy with inhibitors of the EGFR– and VEGF–pathways has shown promising results in early, single–armed studies, but should not be applied in a routine clinical setting. An optimal supportive care remains the basis of treatment of patients with advanced gastric cancer.

Key words

gastric cancer - locally advanced stage - metastatic disease - palliative chemotherapy

Literatur

  • 1 Ajani JA, Moiseyenko VM, Tjulandin S. et al. . Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: The V–325 study group.  J Clin Oncol. 2007;  25 3205-3209
    CrossrefPubMedGoogle Scholar
  • 2 Ajani JA, Moiseyenko VM, Tjulandin S. et al. . Quality of life with docetaxel plus cisplatin and fluorouracil compared with cisplatin and fluorouracil from a phase III trial for advanced gastric or gastroesophageal adenocarcinoma: the V–325 study group.  J Clin Oncol. 2007;  25 3210-3216
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Al–Batran S, Hartmann JT, Hofheinz R. et al. .Modified FOLFOX in combination with docetaxel for patients with metastatic adenocarcinoma of the stomach or gastroesophageal junction: A multicenter phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). ASCO Meeting Abstracts 2007
    Google Scholar
  • 5 Allum WH, Hallissey MT, Ward LC, Hockey MS.. A controlled, prospective, randomised trial of adjuvant chemotherapy or radiotherapy in resectable gastric cancer: interim report. British Stomach Cancer Group.  Br J Cancer. 1989;  60 739-744
    CrossrefPubMedGoogle Scholar
  • 6 Boige V, Pignon J, Saint–Aubert B. et al. .Final results of a randomized trial comparing preoperative 5–fluorouracil(F)/cisplatin(P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD–7–FFCD 9703 trial. ASCO Meeting Abstracts 2007
    Google Scholar
  • 7 Boku N, Yamamoto S, Shirao K. et al. .Randomized phase III study of 5–fluorouracil (5–FU) alone versus combination of irinotecan and cisplatin (CP) versus S–1 alone in advanced gastric cancer (JCOG9912). ASCO Meeting Abstracts 2007
    Google Scholar
  • 8 Bouche O, Raoul JL, Bonnetain F. et al. . Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: A Federation Francophone de Cancerologie Digestive Group Study–FCD 9803.  J Clin Oncol. 2004;  22 4319-44328
    CrossrefPubMedGoogle Scholar
  • 9 Cunningham D, Allum WH, Stenning SP. et al. . Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.  New Engl J Med. 2006;  355 11-20
    CrossrefPubMedGoogle Scholar
  • 10 Cunningham D, Starling N, Rao S. et al. . Capecitabine and oxaliplatin for advanced esophagogastric cancer.  New Engl J Med 2008. 358;  258 336-346
    PubMedGoogle Scholar
  • 11 Di Costanzo F, Gasperoni S, Manzione L. et al. . Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC.  J Natl Cancer Inst. 2008;  100 388-398
    PubMedGoogle Scholar
  • 12 Earle CC, Maroun J.. Adjuvant chemotherapy after curative resection for gastric cancer in non–Asian patients: revisiting a meta–analysis of randomised trials.  Br J Cancer. 1999;  35 1059-1064
    PubMedGoogle Scholar
  • 13 Enzinger PC, Kulke MH, Clark JW. et al. . A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma.  Dig Dis Sci. 2005;  50 2218-2223
    CrossrefPubMedGoogle Scholar
  • 14 Fondevila C, Metges JP, Fuster J. et al. . p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer.  Br J Cancer. 2004;  90 206-215
    CrossrefPubMedGoogle Scholar
  • 15 Glimelius B, Ekström K, Hoffman K. et al. . Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.  Ann Oncol. 1997;  8 163-168
    CrossrefPubMedGoogle Scholar
  • 16 Gotoda T, Yanagisawa A, Sasako M. et al. . Incidence of lymph node metastasis from early gastric cancer: Estimation with a large number of cases at two large centers.  Gastric Cancer. 2000;  3 219-225
    CrossrefPubMedGoogle Scholar
  • 17 Janunger KG, Hafström L, Limelius B.. Chemotherapy in gastric cancer: a review and updated meta–analysis.  Eur J Surg. 2002;  168 597-608
    CrossrefPubMedGoogle Scholar
  • 18 Kang Y, Kang WK, Shin DB. et al. .Randomized phase III trial of capecitabine/cisplatin (XP) vs. continuous infusion of 5–FU/cisplatin (FP) as first–line therapy in patients (pts) with advanced gastric cancer (AGC): Efficacy and safety results. ASCO Annual Meeting 2006
    Google Scholar
  • 19 Köhne CH, Catane R, Klein B. et al. . Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial.  Br J Cancer. 2003;  89 997-1001
    CrossrefPubMedGoogle Scholar
  • 20 Koizumi W, Narahara H, Hara T. et al. . S–1 plus cisplatin versus S–1 alone for first–line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial.  Lancet Oncol. 2008;  9 215-221
    CrossrefPubMedGoogle Scholar
  • 21 Kopp R, Ruge M, Rothbauer E. et al. . Impact of epidermal growth factor (EGF) radioreceptor analysis on long–term survival of gastric cancer patients.  Anticancer Res. 2002;  22 1161-1167
    PubMedGoogle Scholar
  • 22 Krämling HJ, Wilkowski R, Dühmke E. et al. . Adjuvant intraoperative radiotherapy of stomach carcinoma.  Langenbeck Arch Chir Suppl Kongressbd. 1996;  113 211-213
    PubMedGoogle Scholar
  • 23 Lenz HJ, Lee FC, Haller DG. et al. . Extended safety and efficacy data on S–1 plus cisplatin in patients with untreated, advanced gastric carcinoma in a multicenter phase II study.  Cancer. 2007;  109 33-40
    CrossrefPubMedGoogle Scholar
  • 24 Lordick F, Lorenzen S, Hegewisch–Becker S. et al. . Cetuximab plus weekly oxaliplatin/5FU/FA (FUFOX) in 1st line metastatic gastric cancer. Final results from a multicenter phase II study of the AIO upper GI study group.  ASCO (Meeting Abstracts). 2007;  25 4526
    PubMedGoogle Scholar
  • 25 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 1673-1679
    CrossrefPubMedGoogle Scholar
  • 26 Macdonald JS, Smalley SR, Benedetti J. et al. . Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.  New Engl J Med. 2001;  345 725-730
    CrossrefPubMedGoogle Scholar
  • 27 Mari E, Floriani I, Tinazzi A. et al. . Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta–analysis of published randomised trials. A study of the GISCAD.  Ann Oncol. 2000;  11 837-843
    CrossrefPubMedGoogle Scholar
  • 28 Ohtsu A, Boku N, Tamura F. et al. . An early phase II study of a 3–hour infusion of paclitaxel for advanced gastric cancer.  Am J Clin Oncol. 1998;  21 416-419
    CrossrefPubMedGoogle Scholar
  • 29 Panzini I, Gianni L, Fattori PP. et al. . Adjuvant chemotherapy in gastric cancer: a meta–analysis of randomized trials and a comparison with previous meta–analyses.  Tumori. 2002;  88 21-27
    PubMedGoogle Scholar
  • 30 Pinto C, Di F Fabio, Siena S. et al. . Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study).  Ann Oncol. 2007;  18 510-517
    PubMedGoogle Scholar
  • 31 Sakuramoto S, Sasako M, Yamaguchi T. et al. . Adjuvant chemotherapy for gastric cancer with S–1, an oral fluoropyrimidine.  New Engl J Med. 2007;  357 1810-1820
    CrossrefPubMedGoogle Scholar
  • 32 Shah MA, Ramanathan RK, Ilson DH. et al. . Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.  J Clin Oncol. 2006;  24 5201-5206
    CrossrefPubMedGoogle Scholar
  • 33 Sulkes A, Smyth J, Sessa C. et al. . Docetaxel (Taxotere) in advanced gastric cancer: results of a phase II clinical trial. EORTC Early Clinical Trials Group.  Br J Cancer. 1994;  70 380-383
    PubMedGoogle Scholar
  • 34 Van Cutsem E, Dicato M, Arber N. et al. . The neo–adjuvant, surgical and adjuvant treatment of gastric adenocarcinoma. Current expert opinion derived from the Seventh World Congress on Gastrointestinal Cancer, Barcelona, 2005.  Ann Oncol. 2006;  17 13-8
    CrossrefPubMedGoogle Scholar
  • 35 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
    CrossrefPubMedGoogle Scholar
  • 36 Vanhoefer U, Rougier P, Wilke H. et al. . Final results of a randomized phase III trial of sequential high–dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the european organization for research and treatment of cancer gastrointestinal tract cancer cooperative group.  J Clin Oncol. 2000;  18 2648-2657
    PubMedGoogle Scholar
  • 37 Wagner AD, Grothe W, Haerting J. et al. . Chemotherapy in advanced gastric cancer: A systematic review and meta–analysis based on aggregate data.  J Clin Oncol. 2006;  24 2903-2909
    CrossrefPubMedGoogle Scholar
  • 38 Yao JC, Wang L, Wei D. et al. . Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer.  Clin Cancer Res. 2004;  10 4109-4117
    CrossrefPubMedGoogle Scholar

1 Union Internationale Contre le Cancer

2 Randomized ECF for Advanced and Locally advanced esophagogastric cancer 2

3 S–1 Plus cisplatin vs. S–1 In RCT In the Treatment of Stomach cancer

Korrespondenz

Dr. Kerstin Schütte

Klinik für Gastroenterologie, Hepatologie und Infektiologie Otto–von–Guericke–Universität

Leipziger Straße 44

39120 Magdeburg

Email: kerstin.schuette@med.ovgu.de