Dtsch Med Wochenschr 2007; 132(15): 803-807
DOI: 10.1055/s-2007-973624
Aktuelle Diagnostik & Therapie | Review article
Onkologie
© Georg Thieme Verlag KG Stuttgart · New York

Adjuvante Therapie des Pankreaskarzinoms

Adjuvant treatment of pancreatic cancerC. W. Michalski1 , J. Kleeff 1 , D. Jäger 2 , H. Friess 1 , M. W. Büchler1
  • 1Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie, Chirurgische Klinik, Universität Heidelberg
  • 2Medizinische Onkologie, Nationales Centrum für Tumorerkrankungen, Universität Heidelberg
Further Information

Publication History

eingereicht: 29.11.2006

akzeptiert: 27.2.2007

Publication Date:
11 April 2007 (online)

Zusammenfassung

Die komplette (R0) Resektion gefolgt von einer adjuvanten Chemotherapie verbessert signifikant die Prognose von Patienten mit einem Adenokarzinom des Pankreas. Zu diesem Ergebnis kommt eine randomisiert-kontrollierte klinische Studie (RCT) zur adjuvanten Therapie des Pankreaskarzinoms, die ESPAC-1 (European Study Group for Pancreatic Cancer) Studie, eine Meta-Analyse von 5 RCTs zur adjuvanten Therapie, sowie eine erst kürzlich veröffentlichte Studie (RCT) zur adjuvanten Chemotherapie des Pankreaskarzinoms. Sowohl 5-FU als auch Gemcitabin scheinen als adjuvante Therapie effektiv zu sein, und die bald abgeschlossene ESPAC-3 Studie wird zeigen, ob es einen Vorteil für eines der beiden Chemotherapeutika gibt. Eine adjuvante/additive Radiochemotherapie scheint -wenn überhaupt- nur einen möglichen Vorteil bei mikroskopisch nicht kompletter (R1) Resektion zu haben; dies muss sich jedoch erst in RCTs bestätigen, d. h. eine adjuvante Radiochemotherapie sowie adjuvante Kombinations-Chemotherapien sollten nur im Rahmen von klinischen Studien angewendet werden.

Summary

Curative (R0) resection and subsequent adjuvant chemotherapy increases significantly the prognosis of patients suffering from adenocarcinoma of the pancreas. This statement is substantiated by the ESPAC-1 (European Study Group for Pancreatic Cancer) trial, a meta-analysis of 5 RCTs for adjuvant therapy as well as a recent RCT for adjuvant chemotherapy in pancreatic cancer. 5-FU and Gemcitabin seem to be effective in the adjuvant setting, and the ESPAC-3 trial will determine which (if any) chemotherapy is superior. Adjuvant/additive chemoradiation might have its role in a subgroup of patients with positive resection margins (R1), however, this has to be proven in RCTs. Thus, adjuvant chemoradiation and/or adjuvant combination therapies should only be used within clinical trials.

Literatur

  • 1 Ammori J B. et al . Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas.  J Gastrointest Surg. 2003;  7 766-772
  • 2 Bakkevold K E. et al . Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater - results of a controlled, prospective, randomised multicentre study.  Eur J Cancer. 1993;  29A 698-703
  • 3 Bassi C. et al . Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial.  Dig Surg. 2005;  22 353-363
  • 4 Beger H G. et al . Treatment of pancreatic cancer: challenge of the facts.  World J Surg. 2003;  27 1075-1084
  • 5 Bray F. et al . Estimates of cancer incidence and mortality in Europe in 1995.  Eur J Cancer. 2002;  38 99-166
  • 6 Breslin T M. et al . Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration.  Ann Surg Oncol. 2001;  8 123-132
  • 7 Cameron J L. et al . One thousand consecutive pancreaticoduodenectomies.  Ann Surg. 2006;  244 10-15
  • 8 Carpelan-Holmstrom M. et al . Does anyone survive pancreatic ductal adenocarcinoma ? A nationwide study re-evaluating the data of the Finnish Cancer Registry.  Gut. 2005;  54 385-387
  • 9 Cooperman A M. Pancreatic cancer: the bigger picture.  Surg Clin North Am. 2001;  81 557-574
  • 10 Crane C H. et al . The argument for pre-operative chemoradiation for localized, radiographically resectable pancreatic cancer.  Best Pract Res Clin Gastroenterol. 2006;  20 365-382
  • 11 Cress R D. et al . Survival among patients with adenocarcinoma of the pancreas: a population-based study (United States).  Cancer Causes Control. 2006;  17 403-409
  • 12 Evans D B. Preoperative chemoradiation for pancreatic cancer.  Semin Oncol. 2005;  (Suppl 9) 32 S25-29
  • 13 Garofalo M C, Regine W F, Tan M T. On statistical reanalysis, the EORTC trial is a positive trial for adjuvant chemoradiation in pancreatic cancer.  Ann Surg. 2006;  24 332-333 , ; author reply 333.
  • 14 Ghaneh P. et al . The case for adjuvant chemotherapy in pancreatic cancer.  Best Pract Res Clin Gastroenterol. 2006;  20 383-401
  • 15 Gudjonsson B. Cancer of the pancreas. 50 years of surgery.  Cancer. 1987;  60 2284-2303
  • 16 Imamura M. et al . A randomized multicenter trial comparing resection and radiochemotherapy for resectable locally invasive pancreatic cancer.  Surgery. 2004;  136 1003-1011
  • 17 Jemal A. et al . Cancer statistics, 2006.  CA Cancer J Clin. 2006;  56 106-130
  • 18 Kalser M H, Ellenberg S S. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection.  Arch Surg. 1985;  120 899-903
  • 19 Khanna A. et al . Is adjuvant 5-FU-based chemoradiotherapy for resectable pancreatic adenocarcinoma beneficial? A meta-analysis of an unanswered question.  J Gastrointest Surg. 2006;  10 689-697
  • 20 Kleeff J. et al . Pancreatic cancer: from bench to 5-year survival.  Pancreas. 2006;  33 111-118
  • 21 Kleeff J, Friess H, Buchler M W. Neoadjuvant therapy of pancreatic cancer: why the evidence is still so limited.  Br J Surg. 2007;  94 261-262
  • 22 Klinkenbijl J H. et al . Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.  Ann Surg. 1999;  230 776-782 , ; discussion 782 - 4.
  • 23 Knaebel H P. et al . Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma - CapRI: study protocol [ISRCTN62866759].  BMC Cancer. 2005;  5 37
  • 24 Krempien R. et al . Randomized phase II-study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer-PARC: study protocol [ISRCTN56652283].  BMC Cancer. 2005;  5 131
  • 25 Mehta V K. et al . Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas.  J Gastrointest Surg. 2001;  5 27-35
  • 26 Neoptolemos J P. et al . A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.  N Engl J Med. 2004;  350 1200-1210
  • 27 Neoptolemos J P. et al . Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.  Lancet. 2001;  358 1576-1585
  • 28 Oettle H. et al . Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.  J Am Med Assoc. 2007;  297 267-277
  • 29 Picozzi V J, Traverso L W. The Virginia Mason approach to localized pancreatic cancer.  Surg Oncol Clin N Am. 2004;  13 663-674
  • 30 Picozzi V J, Kozarek R A, Traverso L W. Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma.  Am J Surg. 2003;  185 476-480
  • 31 Pisters P W. et al . Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome.  J Clin Oncol. 2002;  20 2537-2544
  • 32 Richter A. et al . Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience.  World J Surg. 2003;  27 324-329
  • 33 Sener S F. et al . Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985 - 1995, using the National Cancer Database.  J Am Coll Surg. 1999;  189 1-7
  • 34 Shrikhande S V. et al . Pancreatic resection for M1 pancreatic ductal adenocarcinoma.  Ann Surg Oncol. 2006;  14 118-127
  • 35 Spanknebel K, Conlon K C. Advances in the surgical management of pancreatic cancer.  Cancer J. 2001;  7 312-323
  • 36 Stocken D D. et al . Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer.  Br J Cancer. 2005;  92 1372-1381
  • 37 Takada T. et al . Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma.  Cancer. 2002;  95 1685-1695
  • 38 Verbeke C S. et al . Redefining the R1 resection in pancreatic cancer.  Br J Surg. 2006;  93 1232-1237
  • 39 Wagner M. et al . Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma.  Br J Surg. 2004;  91 586-594
  • 40 Wayne J D. et al . Localized adenocarcinoma of the pancreas: the rationale for preoperative chemoradiation.  Oncologist. 2002;  7 34-45
  • 41 Zhu A X, Clark J W, Willett C G. Adjuvant therapy for pancreatic cancer: an evolving paradigm.  Surg Oncol Clin N Am. 2004;  13 605-620, viii

Prof. Dr. Markus W. Büchler

Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie, Chirurgische Klinik Universität Heidelberg

Im Neuenheimer Feld 110

69120 Heidelberg

Phone: 06221/566201

Fax: 06221/566903

Email: markus_buechler@med.uni-heidelberg.de

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