Skip to main content
SpringerLink
Log in

Systemische Chemotherapie neuroendokriner Tumoren

Systemic chemotherapy in neuroendocrine tumours

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Systemische Chemotherapien sind bei Karzinoiden und gut differenzierten pankreatischen neuroendokrinen Tumoren (NET) in der Regel erst nach Auschöpfen von Chirurgie, spezifischer symptomatischer Therapien, SSA, IFN-α, lokoregionärer Verfahren und von Radionuklidtherapie indiziert. Wirksame Substanzen sind Doxorubicin, Fluoropyrimidine, Streptozotocin und Alkylanzien. Deren Kombinationen bilden die Standardtherapie. Die Wirksamkeit neuerer Substanzen wie Capecitabin und Gemcitabin als Mono- oder Kombinationstherapie mit Oxaliplatin und Irinotecan sollte in klinischen Studien geprüft werden. Die Expression molekularer Marker wie VEGF/VEGFR und die hohe Ansprechrate auf Therapieverfahren mit antiangiogenetischer Wirkkomponente (intraarterielle Chemoembolisation, IFN-α) lassen auf einen hohen Stellenwert antiangiogenetischer Therapiestrategien hoffen. Die Prognose gering differenzierter neuroendokriner Karzinome mit biologisch agressivem Verhalten ist trotz hoher objektiver Ansprechraten auf platinhaltige Kombinationschemotherapien schlecht. Wegen der biologischen Nähe und Konkordanz im Verhalten unter Chemotherapie sollten vermehrt die Studienergebnisse des kleinzelligen Bronchialkarzinoms (SCLC) für gering differenzierte NET geprüft werden. Dies gilt insbesondere für Irinotecan/Cisplatin, Topotecan, Gemcitabin, Vinorelbin und Oxaliplatin, jedoch auch für dosisintensivierte Therapien mit Stammzellsupport und molecular targets-orientierte Therapien, z. B. mit EGF- oder VEGF-Inhibitoren.

Abstract

Systemic Chemotherapy in carcinoids and well-differentiated pancreatic neuroendocrine tumours (NET) in most cases is indicated when tumours are refractory to symptomatic treatment options, somatostatin analogues, interferon alpha, locoregional intraarterial chemoembolisation and targeted radionuclide therapy. Doxorubicin, Fluoropyrimidines, Streptozotocin and alcylating drugs are active. The standard combination therapy is streptocotocin/doxorubicin. The efficacy of newer drugs like capecitabine and gemcitabine as single agent or in combinations with oxaliplatin and irinotecan has to be investigated in clinical trials. The expression of molecular markers like VEGF/VEGFR as well as the high response rate to therapies with antiangiogenetic components e. g. intraarterial chemoembolisation or interferon alpha indicate the probable importance of antiangogenic therapies. Despite high objective response rates with platinum based chemotherapy the prognosis of poorly-differentiated neuroendocrine tumours with a biologic aggressive behaviour remains poor. Because of the biological similarity and concordance in behaviour under chemotherapy clinical trial results of small cell lung cancer (SCLC) should also be investigated in poorly-differentiated NET, especially topotecan, gemcitabine, vinorelbine, oxaliplatin. The role of dose intensivated chemotherapy with stem cell support and of Molecular targeted therapy e. g. with EGF or VEGF inhibitors should be investigated as well.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Rougier P, Mitry E (2000) Chemotherapy in the treatment of Neuroendocrine Malignant Tumours. Digestion 62 (Suppl 1):73–78

    Article  CAS  Google Scholar 

  2. Solcia E, Klöppel G, Sobin LH in collaboration with 9 pathologists from 4 countries. Histological typing of endocrine tumours. In: International Histological Classification of tumours (2002) World Health Organization Pathology Panel. World Health Organization, 2nd en. Springer, Berlin Heidelberg New York

  3. Schmoll HJ, Schmoll E, Dralle H, Arnold R (1999) Karzinoide. In: Kompendium Internistische Onkologie, 3. Aufl, Bd 2; 41.47, S 1188–1213

  4. Ansell SM, Pitat HC, Burch PA, Kvols LK, Mahoney MR, Rubin J (2001) A phase II study of high-dose paclitaxel in patient with neuroendocrine tumors: Cancer 91:1543–1548

    Google Scholar 

  5. Catena L, Bajetta E, Procopio G, Ferrari L, Della Torre S, Verzoni E, Bichisao E, Buzzoni R, Iacobelli S, Falkone A (2003) Oxaliplatin plus Capecitabine in advanced neuroendocrine tumours (NETS): is the new WHO classification applicable to daily practice. ECCO; #117

  6. Moertel CG, Lefkopoulo M, Lipsitz M, Hahn RG, Klaassen D (1992) Streptozotocin-doxorubicin, Streptozotocin-fluorouracil, or chlorozotocin in the treatment of advanced islet cell carcinoma. N Engl J Med 326:519–523

    CAS  PubMed  Google Scholar 

  7. Andrejev HJN, Scott-Mackie P, Cunningham D et al (1995) Phase II study of continuos infusion fluorouracil and interferon alfa 2-b in the palliation of malignant neuroendocrine tumors. J Clin Oncol 13:1486–1492

    PubMed  Google Scholar 

  8. Saltz L, Kemeny N, Schwartz G, Kelsen D (1994) A phase II trial of alpha-interferon and 5-fluorouracil in patients with advanced carzinoid and islel cell tumors. Cancer 74:958–961

    CAS  PubMed  Google Scholar 

  9. Ahlgen ID, Leming PD, Gullo JJ, Heim WJ, Lokich JJ, Fryer D (1995) Protracted infusional 5-FU (PIF) + [alpha] 2b-interferon ([alpha]-IFN) in metastatic carcinoid: updated experience with Mid-Atlantic Oncology Program (MAOP) study 5190 [abstract # 552]. Proc Am Soc Clin Oncol 14:219

    Google Scholar 

  10. Moertel CG, Hanley JA., Johnson LA (1980) Streptozotocin alone compared with Streptozotocin plus fluorouracil in the treatment of advanced islet cell carcinoma. N Engl J Med 303:1189–94

    CAS  PubMed  Google Scholar 

  11. Strauss GM, Weitzmann SA, Aoki TT (1979) Dimethyltriazenoimidazolecarboxamide therapy of malignant glucagonoma. Ann Intern Med 90:57–58

    CAS  PubMed  Google Scholar 

  12. Stacpoole PW (1981) The glucagonoma syndrome: clinical features, diagnosis and treatment. Endocr Rev 2:347–361

    CAS  PubMed  Google Scholar 

  13. Mitry E, Rougier P (2001) The treatment of undifferentiated neuroendocrine tumors. Crit Rev Oncol Hematol 37 47–51

    Google Scholar 

  14. Seitz JF, Perrier H, Giovanni M, Menges C, Fourdan O, Barrière N, Viens P (1995) Cancers neuroendocrines anaplasiques avancés: Intérêt de l’association VP 16-CDDP. Bull Cancer 82:433–434

    Google Scholar 

  15. Hainsworth JD, Johnson MH, Greco FA (1988) Poorly differentiated neuroendocrine carcinoma of unknown primary site. Ann Intern Med 109:364–371

    CAS  PubMed  Google Scholar 

  16. Mitry E, Baudin E, Ducreux M, Sabourin JC, Rufié P, Aparicio T, Lasser P, Elias D, Duvillard P, Schlumberger M, Rougier P (1999) Treatment of poorly differentiated neuroendocrine tumors with etoposide and cisplatin. Br J Cancer 81:1351–1355

    Article  CAS  PubMed  Google Scholar 

  17. Greco FA, Burris HA 3rd, Erland JB, Gray JR, Kalkmann LA, Schreeder MT, Hainsworth JD (2000) Carcinoma of unknown primary site. Cancer 89:2655–2660

    Article  CAS  PubMed  Google Scholar 

  18. Hainsworth JD, Erland JB, Kalmann LA, Schreeder MT, Greco FA (1997) Carcinoma of unknown primary site: treatment with 1- hour paclitaxel, carboplatin and extended-schedule etoposide. J Clin Oncol 15:2385–2393

    CAS  PubMed  Google Scholar 

  19. Hou Z, Elasmar SA, Lozano R, Hoff P, Wolff RA, Abbruzzese JL, Ajani IA, Carr K, Rashid A, Yao JC (2003) A pilot study of irinotecan plus cisplatin in patients with metastatic high-grade neuroendocrine carcinoma. ASCO # 1508

  20. Ryungsa K, Tetsuya T (2004) Changes in Therapy for Solid Tumors: Potential for Overcoming Drug Resistance In Vivo with Molecular Targeting Agents. Surg Today 34:293–303

    Article  PubMed  Google Scholar 

  21. Johnson BE, Fisher B, Fisher T. Phase II Study of STI 571 for patients small cell lung cancer. Proc Am Soc Clin Oncol 2002

  22. Yao JC, Yeung S.J, Ryshid A, Szklaruk J, Baker J, Carr K, Vauthey N, Ellis L, Curley S, Ajani JA (2003) Early Results of a Phase II Trial of Imatinib in patients with advanced carcinoid tumor. ASCO: # 1491

  23. Hobday TJ, Rubin J, Goldberg R, Erlichman C, Lloyd R (2003) Molecular Markers in Metastatic Gastrointestinal Neuroendocrine tumors: ASCO: # 1078

  24. Kulka M, Bergsland E, Ryan DP, Clark JW, Enzinger PC, Michelini A, Kinsella A, Fogler W, Venook A, Fuchs C (2003) A Phase II, open-label, safety, pharmakokinetic and efficacy study of Recombinant Human Endostatin in Patients with Advanced Neuroendocrine tumors. ASCO: # 958

  25. Grand SC, Kris MG, Houghton AN, Chapman PB (1999) Long survival patients with small cell lung cancer after adjuvant treatment with the antiidiotypic antibody BEC 2 plus Bacillus Calmette Guerin. Clin Cancer Res 5:1319–1323

    CAS  PubMed  Google Scholar 

  26. Mulshine JL, Avis I, Treston AM, et al. (1988) Clinical use of a monoclonal antibody to bombesin-like peptide in patients with lung cancer. Ann New York Acad Sci 547:360–372

    CAS  Google Scholar 

  27. Nakanisi Y, Mulshine JL, Kasprzyk PG (1988) Insulin-like growth factor-1 can mediate autocrine proliferation of human small cell lung cancer cell lines in vitro. J Clin Invest 82:354–359

    PubMed  Google Scholar 

  28. Krystal GW, Hines SJ, Organ CP (1996) Autocrine growth of small cell lung cancer mediated by coexpression of c-kit and stem cell factor. Cancer Res 56:370–376

    CAS  PubMed  Google Scholar 

  29. Rudin C, Otterson GA, Mauer AN et al. (2002) Pilot trial of G3139, a bcl-2 antisense oligo nucleotide, and paclitaxel in patients with chemorefractory small cell lung cancer. Ann Oncol 13:39–45

    Article  PubMed  Google Scholar 

  30. Jett JR, Maksymiuk AW, Su JQ, Mailliard JA, Krook JE, Tschetter LK, Kardinal CG, Twito T, Levitt R, Gerstner JR (1994) Phase III trial of recombinant interferon gamma in complete responders with small cell lung cancer. J Clin Oncol 12:321–326

    Google Scholar 

  31. Kelly K, Crowley JJ, Bunn PA, Hazuka MB, Beasley K, Upchurch C, Weiss GR, Hicks WJ, Gandara DR, Rivkin S (1995) Role of recombinant interferon alpha-2 a maintenance in patients with limited stage small cell lung cancer responding to concurent chemoradiation: a South West Oncology Group Study. J Clin Oncol 13:2924–2930

    CAS  PubMed  Google Scholar 

  32. Shepherd FA, Giaccone L, Seymour L, Debruyne C, Bezjak A, Hirsh V, Smylie, M, Rubin S, Martins H, Lamont A, Krzakowski m, Sadura a, Zee B (2002) Prospective randomized, double-blind placebo controlled trial of marimastat after response to first-line chemotherapy in patients with small cell lung cancer: a trial of the National Cancer Institute of Canada Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol 20:4434–4439

    Article  CAS  PubMed  Google Scholar 

  33. Shepherd FA (2001) Alternatives to chemotherapy and radiotherapy in treatment of small cell lung cancer. Semin Oncol 28:30–37

    Article  CAS  Google Scholar 

  34. Simon M, Argiris A, Murren JR (2004) Progress in therapy of small cell lung cancer. Critical Reviews in Oncology/Hematology 49:119–133

    Google Scholar 

  35. Noda K, Nishiwaki Y, Kawaharo M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe, K Tamura T Yamamota S, Sajio N (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer, New Engl J Med 346:85–91

    Google Scholar 

  36. James LE, Rudd R, Gower NH et al. (2002) A phase III randomised comparison of gemcitabin/carboplatin (GC) with cisplatin/etoposide (PE) in patients with poor prognosis small cell lung cancer (SCLC). Prac Am Soc Clin Oncol

  37. Elias A (2001) Dose intensification of chemotherapy in SCLL: pro. controversies in lung cancer, a multidisciplinary approach by B. Movsas et al., Dekker, pp 91–106

    Google Scholar 

  38. Leyvraz S, Perey L, Rosti G, et. al. 81999) Multiple courses of high-dose ifosfamide, carboplatin and etoposide with peripheral-blood progenitor cells and filgrastim for small-cell lung cancer: a feasability study by the European Group for Blood and Bone Marrow Transplantation. J Clin Oncol 17:3531–3539

    Google Scholar 

  39. Jensen RT, Doherty GM (2001) Carcinoid Tumors and the Carcinoid Syndrome. In: Devita VT, Hellmann S, Rosenberg SA (eds) Principles and Practice of Oncology Ch 38.6, 6th en. Lipincott Williams & Wilkins

  40. Kvols L, Perry R, Vinik A, Wu LT, Chanian P, Baylin S, Thompson N (2000) Neoplasms of the neuroendocrine system and Neoplasms of the Gastroenteropancreatic endocrine system. In: Cancer Medicine, 5th en, Ch 85. Decker inc. Haemilton, London, pp 1121–1172

  41. Sridhar SS, Shepherd TA (2003) Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer. Lung cancer 42:81–91

    Article  Google Scholar 

Download references

Interessenkonflikt:

Keine Angaben

Author information

Authors and Affiliations

  1. Medizinische Universitätsklinik IV, Onkologie und Hämatologie, Martin-Luther-Universität Halle-Wittenberg

    T. Kegel & H.-J. Schmoll

  2. Medizinische Universitätsklinik IV, Onkologie und Hämatologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 , Halle (Saale)

    T. Kegel

Authors
  1. T. Kegel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H.-J. Schmoll
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Kegel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kegel, T., Schmoll, HJ. Systemische Chemotherapie neuroendokriner Tumoren. Onkologe 10, 621–633 (2004). https://doi.org/10.1007/s00761-004-0730-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-004-0730-3

Schlüsselwörter

Keywords

Search

Navigation