Neoadjuvante und adjuvante Therapie des Magenkarzinoms

Zusammenfassung

Neoadjuvante und adjuvante Therapiemodalitäten sind häufig bei lokal-fortgeschrittenen Magenkarzinomen eingesetzt worden. Die adjuvante Chemotherapie wird bis dato nicht als sehr gewinnbringend eingestuft und ist nach wie vor eine experimentelle Therapie. Seit der Veröffentlichung des Intergroup Trials 0116 im September 2001 wird die adjuvante Radiochemotherapie als Standardtherapie beim nodal-positiven Magenkarzinom in den USA empfohlen. Diese Studie ist aber in Europa und Japan heftig kritisiert worden, insbesondere aufgrund der inadäquaten Resektion. So erhielten 54 % der Patienten weniger als eine D1-Lymphadenektomie. Die neoadjuvante Chemotherapie erscheint sinnvoll, allerdings gibt es bis dato nur eine große randomisierte Studie aus Grossbritannien (die so genannte MAGIC Studie). Auch diese Studie hat inhärente Probleme, wie z. B. das minimalistische Staging, Defizite in der chirurgischen und histopathologischen Qualitätskontrolle (z. B. keine Angaben zur Häufigkeit der R1-Resektionen) und durch den Einschluss von Adenokarzinomen des distalen Ösophagus. Momentan kann keine der genannten multimodalen Therapieprinzipien als Standard bei der Behandlung des Magenkarzinoms empfohlen werden. Patienten, die diese Therapieformen erhalten, sollten bevorzugt innerhalb von kontrollierten Studien behandelt werden.

Abstract

Neoadjuvant and adjuvant treatment modalities have been tested widely in locally advanced gastric cancers. Adjuvant chemotherapy is not considered to be of significant benefit and such therapy for patients with resected gastric cancer is investigational. In the USA, the use of postoperative radiochemotherapy is considered a standard of care after the publication of the Intergroup Study 0116 in September 2001. The study has been heavily criticized in Europe and Japan mainly due to inadequate surgery as 54 % of the patients received less than a D1-lymphadenectomy. Neoadjuvant chemotherapy appears to be attractive however, only one larger randomized trial has currently been reported from the United Kingdom (the so-called MAGIC Trial). This trial again has some inherent problems with minimal pretherapeutic staging, deficits in surgical and pathological quality control (i. e. frequency of R1-resections is unknown) and inclusion of esophageal adenocarcinomas. Currently none of these treatment modalities can be recommended as standard of care and patients receiving this type of treatment should therefore exclusively been treated within controlled trials.

multimodale Therapie - Chemotherapie - adjuvante Therapie - Radiochemotherapie - neoadjuvante Therapie - Magenkarzinom

multimodality treatment - chemotherapy - adjuvant therapy - chemoradiotherapy - neoadjuvant therapy - gastric cancer

Literatur

• 1 Ajani J A, Ota D M, Jessup J M. et al . Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy.  Cancer. 1991;  68 1501-1506
• 2 Alexander H R, Grem J L, Pass H I. et al . Neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma.  Oncology. 1993;  7 37-42
• 3 Allum W CD, Weeden S. for the UK NCRI Upper GI Clinical Studies Group . Perioperative chemotherapy in operable gastric and lower oesophageal cancer: a randomized, controlled trial (the MAGIC trial, ISRCTN 93793971).  Proc Am Soc Clin Oncol. 2003;  20 249a
• 4 Bajetta E, Buzzoni R, Mariani L. et al . Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group.  Ann Oncol. 2002;  13 299-307
• 5 Bleiberg H, Goffin J C, Dalesio O. et al . Adjuvant radiotherapy and chemotherapy in resectable gastric cancer. A randomized trial of the gastro-intestinal tract cancer cooperative group of the EORTC.  Eur J Surg Oncol. 1989;  15 535-543
• 6 Bollschweiler E, Schröder W, Hölscher A H, Siewert J R. Preoperative risk analysis in patients with adenocarcinoma or squamous cell carcinoma of the oesophagus.  Br J Surg. 2000;  87 1106-1110
• 7 Bollschweiler E, Wolfgarten E, Gutschow C, Holscher A H. Demographic variations in the rising incidence of esophageal adenocarcinoma in white males.  Cancer. 2001;  92 549-555
• 8 Chang H M, Jung K H, Kim T Y. et al . A phase III randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil and mitomycin C versus 5-fluorouracil alone in curatively resected gastric cancer.  Ann Oncol. 2002;  13 1779-1785
• 9 Crookes P, Leichman C G, Leichman L. et al . Systemic chemotherapy for gastric carcinoma followed by postoperative intraperitoneal therapy: a final report.  Cancer. 1997;  79 1767-75
• 10 De Potter T, Flamen P, Van Cutsem E. et al . Whole-body PET with FDG for the diagnosis of recurrent gastric cancer.  Eur J Nucl Med Mol Imaging. 2002;  29 525-529
• 11 Dent D M, Werner I D, Novis B. et al . Prospective randomized trial of combined oncological therapy for gastric carcinoma.  Cancer. 1979;  44 385-391
• 12 Dittler H J. [Surgical endoscopy for staging and the selection of procedure].  Chirurg. 2002;  73 2-8
• 13 Gez E, Sulkes A, Yablonsky-Peretz T, Weshler Z. Combined 5-fluorouracil (5-FU) and radiation therapy following resection of locally advanced gastric carcinoma.  J Surg Oncol. 1986;  31 139-142
• 14 Greenlee R T, Murray T, Bolden S, Wingo P A. Cancer statistics, 2000.  CA Cancer J Clin. 2000;  50 7-33
• 15 Group GTS . A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma. Gastrointestinal Tumor Study Group.  Cancer. 1982;  49 1771-1777
• 16 Gunderson L L, Hoskins R B, Cohen A C. et al . Combined modality treatment of gastric cancer.  Int J Radiat Oncol Biol Phys. 1983;  9 965-975
• 17 Hartgrink H H, Putter H, Klein Kranenbarg E. et al . Value of palliative resection in gastric cancer.  Br J Surg. 2002;  89 1438-1443
• 18 Hayes N, Wayman J, Wadehra V. et al . Peritoneal cytology in the surgical evaluation of gastric carcinoma.  Br J Cancer. 1999;  79 520-524
• 19 Henning G T, Schild S E, Stafford S L. et al . Results of irradiation or chemoirradiation following resection of gastric adenocarcinoma.  Int J Radiat Oncol Biol Phys. 2000;  46 589-598
• 20 Hundahl S A, Menck H R, Mansour E G, Winchester D P. The National Cancer Data Base report on gastric carcinoma.  Cancer. 1997;  80 2333-2341
• 21 Kelsen D, Karpeh M, Schwartz G. et al . Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil.  J Clin Oncol. 1996;  14 1818-1828
• 22 Landry J, Tepper J E, Wood W C. et al . Patterns of failure following curative resection of gastric carcinoma.  Int J Radiat Oncol Biol Phys. 1990;  19 1357-1362
• 23 Langley S M, Alexiou C, Bailey D H, Weeden D F. The influence of perioperative blood transfusion on survival after esophageal resection for carcinoma.  Ann Thorac Surg. 2002;  73 1704-1709
• 24 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
• 25 Macadam R, Sarela A, Wilson J. et al . Bone marrow micrometastases predict early post-operative recurrence following surgical resection of oesophageal and gastric carcinoma.  Eur J Surg Oncol. 2003;  29 450-454
• 26 Macdonald J S, Fleming T R, Peterson R F. et al . Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study.  Ann Surg Oncol. 1995;  2 488-494
• 27 Macdonald J S, Smalley S R, Benedetti J. et al . Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.  N Engl J Med. 2001;  345 725-730
• 28 McCulloch P, Nita M E, Kazi H, Gama-Rodrigues J. Extended versus limited lymph nodes dissection technique for adenocarcinoma of the stomach. Cochrane Database Syst Rec CD 001964 2004
• 29 Moertel C G, Childs D S, O'Fallon J R. et al . Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma.  J Clin Oncol. 1984;  2 1249-1254
• 30 Neri B, Cini G, Andreoli F. et al . Randomized trial of adjuvant chemotherapy versus control after curative resection for gastric cancer: 5-year follow-up.  Br J Cancer. 2001;  84 878-880
• 31 Parker S L, Tong T, Bolden S, Wingo P A. Cancer statistics, 1997.  CA Cancer J Clin. 1997;  47 5-27
• 32 Regine W F, Mohiuddin M. Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach.  Int J Radiat Oncol Biol Phys. 1992;  24 921-927
• 33 Schuhmacher C P, Fink U, Becker K. et al . Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up.  Cancer. 2001;  91 918-927
• 34 Siewert J R, Holscher A H, Becker K, Gossner W. [Cardia cancer: attempt at a therapeutically relevant classification].  Chirurg. 1987;  58 25-32
• 35 Siewert J R, Fink U, Sendler A. et al . Gastric Cancer.  Curr Probl Surg. 1997;  34 835-939
• 36 Siewert J R, Bottcher K, Stein H J, Roder J D. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study.  Ann Surg. 1998;  228 449-461
• 37 Siewert J R, Feith M, Werner M, Stein H J. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1 002 consecutive patients.  Ann Surg. 2000;  232 353-361
• 38 van de Velde C J, Peeters K C. The gastric cancer treatment controversy.  J Clin Oncol. 2003;  21 2234-2236
• 39 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
• 40 Yu W, Seo B Y, Chung H Y. Postoperative body-weight loss and survival after curative resection for gastric cancer.  Br J Surg. 2002;  89 467-470