Diagnostik, Staging und Therapie des Magenkarzinoms

Zusammenfassung

Während die Inzidenz des Magenkarzinoms im Westen kontinuierlich sinkt, stellt es weltweit nach wie vor eine der häufigsten tumorbedingten Todesursachen dar. Für die große Mehrheit der sporadischen Tumoren ist die molekulare Pathogenese weiterhin im Detail ungeklärt, für einzelne familiäre Karzinomformen konnten ursächliche Keimbahnmutationen detektiert werden. Nur die onkologisch radikale Resektion bietet Aussicht auf Heilung, dabei wird die Prognose vom Tumorstadium bestimmt - leider befinden sich im Westen noch immer etwa zwei Drittel der Patienten in einem fortgeschrittenen Stadium bei Diagnose.

Die Ergebnisse der chirurgischen Therapie sind auf einem Plateau angelangt, im Stadium IIIB und IV (UICC) gelingt nur in etwa 40 % eine prognostisch entscheidende R0-Resektion, und auch bei erfolgter kurativer Resektion ist die Rezidivrate - stadienabhängig - sehr hoch. Der Nutzen einer neoadjuvanten Chemotherapie bei lokal irresektablen Tumoren konnte in Phase-II-Studien hinreichend belegt werden. Weniger klar ist das Vorgehen in der adjuvanten Situation: Hier gilt es, den Nutzen einer Radiochemotherapie auch unter erfolgter systematischer Lymphadenektomie zu beweisen. In der palliativen Situation gelten derzeit platinbasierte 5-FU-Hochdosisprotokolle als Standard, dem sich moderne Substanzen wie Taxane oder Irinotecan bislang nicht als überlegen erwiesen haben.

Abstract

In spite of a continuously decreasing incidence in Western countries, gastric cancer remains a major health problem world-wide and a leading cause of cancer-related deaths. The molecular pathogenesis of the vast majority of sporadic tumours has not yet been clarified in detail, while for some familial cancer types causal germline mutations have been identified. Only radical resection offers a chance of cure and the prognosis is determined by the stage of disease at diagnosis. Unfortunately, about two-thirds of patients are still diagnosed in a late stage. The results of surgery have reached a plateau of effectiveness, in stages III and IV (UICC) an R0 resection will be possible in only about 40 % of cases and even, after successful curative resection, the prognosis is limited due to a high recurrence rate. The benefit of neoadjuvant chemotherapy in locally advanced cancers has been verified in phase II studies. Less clear is the adjuvant situation - the benefit of adjuvant radiochemotherapy after systematic lymphadenectomy awaits to be proven. In the palliative situation platinum-based high-dose 5-FU infusion protocols are currently the standard therapy.

Magenkarzinom - Diagnostik - Staging - Therapie - adjuvant - neoadjuvant - palliativ - Übersicht

Gastric cancer - diagnosis - staging - therapy - adjuvant - neoadjuvant - palliative - review

Literatur

• 1 Boring C C, Squires T S, Tong T. et al . Cancer statistics, 1994.  CA Cancer J Clin. 1994;  44 7-26
• 2 Guiraldes E, Pena A, Duarte I. et al . Nature and extent of gastric lesions in symptomatic Chilean children with Helicobacter pylori-associated gastritis.  Acta Paediatr. 2002;  91 39-44
• 3 Richards F M, McKee S A, Rajpar M H. et al . Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.  Hum Mol Genet. 1999;  8 607-610
• 4 Becker K F, Keller G, Hoefler H. The use of molecular biology in diagnosis and prognosis of gastric cancer.  Surg Oncol. 2000;  9 5-11
• 5 Stadtlander C T, Waterbor J W. Molecular epidemiology, pathogenesis and prevention of gastric cancer.  Carcinogenesis. 1999;  20 2195-2208
• 6 Graham D Y, Schwartz J T, Cain G D. et al . Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma.  Gastroenterology. 1982;  82 228-231
• 7 Kelly S, Harris K M, Berry E. et al . A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma.  Gut. 2001;  49 534-539
• 8 Lehnert T, Rudek B, Kienle P. et al . Impact of diagnostic laparoscopy on the management of gastric cancer: prospective study of 120 consecutive patients with primary gastric adenocarcinoma.  Br J Surg. 2002;  89 471-475
• 9 Bryan R T, Cruickshank N R, Needham S J. et al . Laparoscopic peritoneal lavage in staging gastric and oesophageal cancer.  Eur J Surg Oncol. 2001;  27 291-297
• 10 Roder J D, Bottcher K, Siewert J R. et al . Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992.  Cancer. 1993;  72 2089-2097
• 11 Wilke H, Stahl M. Magenkarzinom. Schmoll HH, Höffken K, Possinger K Kompendium internistische Onkologie. Springer, 1999: 895-920
• 12 Bonenkamp J J, Songun I, Hermans J. et al . Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients.  Lancet. 1995;  345 745-748
• 13 Cuschieri A, Weeden S, Fielding J. 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 1522-1530
• 14 Wilke H, Preusser P, Fink U. et al . Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin.  J Clin Oncol. 1989;  7 1318-1326
• 15 Plukker J T, Mulder N H, Sleijfer D T. et al . Chemotherapy and surgery for locally advanced cancer of the cardia and fundus: phase II study with methotrexate and 5-fluorouracil.  Br J Surg. 1991;  78 955-958
• 16 Lerner A, Gonin R, Steele G DJ. et al . Etoposide, doxorubicin, and cisplatin chemotherapy for advanced gastric adenocarcinoma: results of a phase II trial.  J Clin Oncol. 1992;  10 536-540
• 17 Cascinu S, Labianca R, Graziano F. et al . Intensive weekly chemotherapy for locally advanced gastric cancer using 5-fluorouracil, cisplatin, epidoxorubicin, 6S-leucovorin, glutathione and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).  Br J Cancer. 1998;  78 390-393
• 18 Gallardo-Rincon D, Onate-Ocana L F, Calderillo-Ruiz G. Neoadjuvant chemotherapy with P-ELF (cisplatin, etoposide, leucovorin, 5-fluorouracil) followed by radical resection in patients with initially unresectable gastric adenocarcinoma: a phase II study.  Ann Surg Oncol. 2000;  7 45-50
• 19 Menges M, Schmidt C, Lindemann W. et al . Low toxic neoadjuvant cisplatin, 5-fluorouracil and folinic acid in locally advanced gastric cancer yields high R-0 resection rate.  J Cancer Res Clin Oncol. 2003;  129 423-429
• 20 Allum W, Cunningham D, Weeden S. Perioperative chemotherapy in operable gastric and lower oesophageal cancer: A randomised, controlled trial (the MAGIC trial).  Proc Am Soc Clin Oncol. 2003;  22: 249; abstr. 998
• 21 Hermans J, Bonenkamp J J, Boon M C. et al . Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials.  J Clin Oncol. 1993;  11 1441-1447
• 22 Earle C C, Maroun J A. Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: revisiting a meta-analysis of randomised trials.  Eur J Cancer. 1999;  35 1059-1064
• 23 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 (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente).  Ann Oncol. 2000;  11 837-843
• 24 Macdonald J S, Smalley S R, Benedetti J. et al . Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophagel junction.  N Engl J Med. 2001;  345 725-730
• 25 Pyrhonen S, Kuitunen T, Nyandoto P. et al . Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer.  Br J Cancer. 1995;  71 587-591
• 26 Glimelius B, Ekstrom 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
• 27 Wils J A, Klein H O, Wagener D J. et al . Sequential high-dose methotrexate and fluorouracil combined with doxorubicin - a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group.  J Clin Oncol. 1991;  9 827-831
• 28 Webb A, Cunningham D, Scarffe J H. et al . Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.  J Clin Oncol. 1997;  15 261-267
• 29 Ajani J, van Cutsem E, Moiseyenko V. et al . Docetaxel, cisplatin, 5-fluorouracil compared to cisplatin and 5-fluorouracil for chemonaive patients with metastasic or locally recurrent, unresectable gastric carcinoma (MGC): Interim results of a randomized phase III trial.  Proc Am Soc Clin Oncol. 2003;  22: 249; abstract 999
• 30 Pozzo C, Bugat R Peschel C. et al . Irinotecan in combination with CDDP or 5-FU and folinic acid is active in patients with advanced gastric of gastro-oesophageal junction adenocarcinoma: final results of a randomized phase II study.  Proc Am Soc Clin Oncol. 2001;  20 abstract 531
• 31 Bouche O, Raoul J L, Giovanini M. et al . Randomized phase II trial of LV5FU2, LV5FU2-cisplatinum or LV5FU2-irinotecan in patients (pts) with metastatic gastric or cardial adenocarcinoma (MGA): Final results of study FFCD 9803.  Proc Am Soc Clin Oncol. 2003;  22 abstract 1033
• 32 Louvet C, Andre T, Tigaud J M. et al . Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients.  J Clin Oncol. 2002;  20 4543-4548
• 33 Sumpter K A, Harper-Wynne C, Cunningham D. et al . Randomised, multicenter phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer: Confirmation of dose escalation.  Proc Am Soc Clin Oncol. 2003;  22 abstract 1031
• 34 Wilke H, Korn M, Vanhofer U. et al . Weekly infusional 5-fluorouracil plus/minus other drugs for the treatment of advanced gastric cancer.  J Infus Chemother. 1996;  6 123-126
• 35 Graziano F, Santini D, Testa E. et al . A phase II study of weekly cisplatin, 6S-stereoisomer leucovorin and fluorouracil as first-line chemotherapy for elderly patients with advanced gastric cancer.  Br J Cancer. 2003;  89 1428-1432
• 36 Kono K, Takahashi A, Amemiya H. et al . Frequencies of HER-2/neu overexpression relating to HLA haplotype in patients with gastric cancer.  Int J Cancer. 2002;  98 216-220
• 37 Takehana T, Kunitomo K, Kono K. et al . Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay.  Int J Cancer. 2002;  98 833-837
• 38 Allgayer H, Babic R, Gruetzner K U. et al . c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems.  J Clin Oncol. 2000;  18 2201-2209
• 39 Hecht J R, Ajani J A, Michaeli D. A multicenter phase II study of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination with G17DT immunogen in patients with locally recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction previously untreated for advanced disease.  Proc Am Soc Clin Oncol. 2003;  22: 258; abstract 1035