Skip to main content

Advertisement

SpringerLink
Log in

Pancreatic cancer — Palliative therapy: chemotherapy

  • Published:
The Chinese-German Journal of Clinical Oncology

Abstract

Single-agent Gemcitabine has been the standard treatment for advanced pancreatic adenocarcinoma in the past years. Due to the aggressive and often chemotherapy-refractory character of this malignancy, systemic treatment options still remain limited. Many combination therapies have been evaluated in clinical trials to improve survival over Gemcitabine alone, until recently without satisfying results. Based on the positive results of a recent randomized trial, the combination of Gemcitabine and Capecitabine might become a new standard as first-line treatment for advanced pancreatic cancer. The clinical advantage of Erlotinib as a novel targeted agent in combination with Gemcitabine seems to be only marginal. Due to the small number of studies, there is still no standard of care in second-line therapy, but Oxaliplatin seems to be an active treatment option in Gemcitabine refractory disease. This article will review the development of cytotoxic antitumoral treatment for advanced pancreatic adenocarcinoma (locally advanced, irresectable and/or metastatic disease) including monotherapies and newer approaches with combination therapies.

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

Similar content being viewed by others

References

  1. Fernandez E, La-Vecchia C, Porta M, et al. Trends in pancreatic cancer mortality in Europe 1955–1989. Int J Cancer, 1994, 57: 786–792.

    Article  CAS  PubMed  Google Scholar 

  2. Jemal A, Murray T. Cancer statistics, 2005. CA Cancer J Clin, 2005, 55: 10.

    Article  PubMed  Google Scholar 

  3. Bruns C, Diebold J, Heinemann V, et al. Karzinome des exokrinen pankreas und der periampullären region. In: Manual gastrointestinale tumoren, 7th ed. München: W. Zuckschwerdt Verlag, 2006. 77–79.

    Google Scholar 

  4. Li D, Xie K, Wolf R, et al. Pancreatic cancer. Lancet, 2004, 363: 1049–1057.

    Article  CAS  PubMed  Google Scholar 

  5. Sant M, Aareleid T, Berrino F, et al. EUROCARE-3: survival of cancer patients diagnosed 1990–94 — results and commantary. Ann Oncol, 2003, 14(Suppl 5): v61–v118.

    Article  PubMed  Google Scholar 

  6. Picozzi VJ, Kozarek RA, Traverso LW. Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg, 2003, 185: 476–480.

    Article  PubMed  Google Scholar 

  7. Bakkevold KE, Arnesjo B, Dahl O, 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.

    Article  CAS  PubMed  Google Scholar 

  8. Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg, 1993, 165: 68–72.

    Article  CAS  PubMed  Google Scholar 

  9. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med, 2004, 350: 1200–1210.

    Article  CAS  PubMed  Google Scholar 

  10. Neoptolemus JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet, 2001, 358: 1576–1585.

    Article  Google Scholar 

  11. Strumberg D, Oettle H, Heinemann V, et al. Pankreaskarzinom. In: Schmoll, Höffken, Possinger, eds. Kompendium internistische onkologie. 4th ed. Heidelberg: Springer Verlag, 2006. 3973–3974.

    Google Scholar 

  12. Kalser MH, Barkin J, Maclntyre JM. Pancreatic cancer. Assessment of prognosis by clinical presentation. Cancer, 1985, 56: 397–402.

    Article  CAS  PubMed  Google Scholar 

  13. Bakkevold KE, Arnesjo B, Kambestad B. Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs and diagnosis related to stage and tumor site. Scand J Gastroenterol, 1992, 27: 317–325.

    Article  CAS  PubMed  Google Scholar 

  14. Glimelius B, Hoffman K, Sjoden PO, et al. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol, 1996, 7: 593–600.

    Article  CAS  PubMed  Google Scholar 

  15. Palmer KR, Kerr M, Knowles G, et al. Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Surg, 1994, 81: 882–885.

    Article  CAS  PubMed  Google Scholar 

  16. Mallinson CN, Rake MO, Cocking JB, et al. Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomized, multicentre trial. Br Med J, 1980, 281: 1589–1591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fung MC, Takayama SW, Ishiguro H, et al. Chemotherapy for advanced or metastatic pancreatic cancer: analysis of 43 randomized trials in 3 decades (1974–2002). Gan To Kagaku Ryoho, 2003, 30: 1101–1111.

    PubMed  Google Scholar 

  18. Rothenberg ML, Moore MJ, Cripps MC, et al. A phase Il trial of Gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol, 1996, 7: 347–353.

    Article  CAS  PubMed  Google Scholar 

  19. Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with Gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol, 1997, 15: 2403–2413.

    CAS  PubMed  Google Scholar 

  20. Tempero M, Plunkett W, Ruiz van Haperen V, et al. Randomized phase II comparison of dose-intense Gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol, 2003, 21: 3402–3408.

    Article  CAS  PubMed  Google Scholar 

  21. Poplin E, Levy ED, Berlin J, et al. Phase III trial of Gemcitabine (30-minute-infusion) versus Gemcitabine (fixed-dose-rate infusion, FDR) versus Gemcitabine and Oxaliplatin in patients with advanced pancreatic cancer (E6201). J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I, 2006, 24(Suppl): LBA4004.

  22. Van Rijswijk REN, Jeziorski K, Wagener DJTH, et al. Weekly highdose 5-Fluorouracil and Folinic acid in metastatic pancreatic carcinoma: a phase II study of the EORTC Gastrointestinal Tract Cancer Coopperative Group. Eur J Cancer, 2004, 40: 2077–2081.

    Article  PubMed  Google Scholar 

  23. Cartwright TH, Cohen A, Varkey JA, et al. Phase II study of oral Capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncl, 2002, 20: 160–164.

    Article  CAS  Google Scholar 

  24. Rougiers P, Adenis A, Ducreux M, et al. A phase II study: Docetaxel as first-line chemotherapy for advanced pancreatic adenocarcinoma. Eur J Cancer, 2000, 36: 1016–1025.

    Article  Google Scholar 

  25. Okada S, Sakata Y, Matsuno S, et al. Phase II study of Docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Br J Cancer, 1999, 80: 438–443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lenzi R, Yalcin S, Evans DB, et al. Phase II study of Docetaxel in patients with pancreatic cancer previously untreated with cytotoxic chemotherapy. Cancer Invest, 2002, 20: 464–472.

    Article  CAS  PubMed  Google Scholar 

  27. Konstadoulakis MM, Antonakis PT, Tsibloulis BG, et al. A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol, 2001, 48: 417–420.

    Article  CAS  PubMed  Google Scholar 

  28. Wagener DJ, Verdonk HE, Dirix LY, et al. Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. Ann Oncol, 1995, 6: 102–104.

    Google Scholar 

  29. O’Reilly S, Donehower RC, Rowinsky EK, et al. A phase II trial of Topotecan in patients with previously untreated pancreatic cancer. Anticancer Drugs, 1996, 7: 410–414.

    Article  PubMed  Google Scholar 

  30. Berlin JD, Catalano P, Thomas JP, et al. Phase III study of Gemcitabine in combination with Fluorouracil versus Gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol, 2002, 20: 3270–3275.

    Article  CAS  PubMed  Google Scholar 

  31. Costanzo FD, Carlini P, Doni L, et al. Gemcitabine with or without continous infusion 5-FU in advanced pancreatic cancer: a randomized phase II trial of the Italian Oncology Group for Clinical Research (GOIRC). Br J Cancer, 2005, 93: 185–189.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Louvet C, Andre T, Lledo G, et al. Gemcitabine combined with Oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol, 2002, 11: 1309–1311.

    Google Scholar 

  33. Louvet C, Labianca R, Hammel P, et al. Gemcitabine in combination with Oxaliplatin compared with Gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol, 2005, 23: 3509–3516.

    Article  CAS  PubMed  Google Scholar 

  34. Heinemann V, Wilke H, Mergenthaler HG, et al. Gemcitabine and Cisplatin in the treatment of advanced or metastatic pancreatic cancer. Ann Oncol, 2000, 11: 1399–1403.

    Article  CAS  PubMed  Google Scholar 

  35. Philip PA, Zalupski MM, Vaitkevicius VK, et al. Phase II study of Gemcitabine and Cisplatin in the treatment of patients with advanced pancreatic carcinoma. Cancer, 2001, 92: 569–577.

    Article  CAS  PubMed  Google Scholar 

  36. Heinemann V, Quietzsch D, Gieseler F, et al. Phase III trial comparing Gemcitabine plus Cisplatin vs. Gemcitabine alone in advanced pancreatic carcinoma. Proc Am Soc Clin Oncol, 2003, 22: 250.

    Google Scholar 

  37. Colucci G, Giuliani F, Gebbia V, et al. Gemcitabine alone or with Cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell’ltalia Meridionale. Cancer, 2002, 94: 902–910.

    Article  CAS  PubMed  Google Scholar 

  38. Louvet C, Hincke A, Labianca R, et al. Increased survival using platinum analog combined with Gemcitabine as compared to Gemcitabine single agent in advanced pancreatic cancer (APC): pooled analysis of two randomized trials, the GERCOR/GISCAD Intergroup Study and a German Multicenter Study. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I, 2006, 24 (Suppl): 4003.

    Article  Google Scholar 

  39. Rocha Lima CM, Green MR, Rotche R, et al. Irinotecan plus Gemcitabine results in no survival advantage compared with Gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol, 2004, 22: 3776–3783.

    Article  CAS  PubMed  Google Scholar 

  40. Oettle H, Richards D, Ramanathan RK, et al. A phase III trial of Pemetrexed plus Gemcitabine versus Gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol, 2005, 16: 1639–1645.

    Article  CAS  PubMed  Google Scholar 

  41. Hedy L, Kindler HL, Dugan W, et al. Clinical outcome in patients with advanced pancreatic cancer treated with Pemetrexed/Gemcitabine. Proc Am Soc Clin Oncol, 2002, 21: 499.

    Google Scholar 

  42. Conroy T, Paillot B, Francois E, et al. Irinotecan plus Oxaliplatin and Leucovorin-modulated Fluorouracil in advanced pancreatic cancer — a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol, 2005, 23: 1228–1236.

    Article  CAS  PubMed  Google Scholar 

  43. Hess V, Salzberg M, Borner M, et al. Combining Capecitabine and Gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial. J Clin Oncol, 2003, 21: 66–68.

    Article  CAS  PubMed  Google Scholar 

  44. Scheithauer W, Schull B, Ulrich-Pur H, et al. Biweekly high-dose Gemcitabine alone or in combination with Capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized pase II trial. Ann Oncol, 2003, 14: 97–104.

    Article  CAS  PubMed  Google Scholar 

  45. Herrmann R, Bodoky G, Ruhstaller T, et al. Gemcitabine (G) plus Capecitabine (C) versus G alone in locally advanced or metastatic pancreatic cancer. A randomized phase III study of the Swiss Group for Clinical Cancer Research (SAKK) and the Central European Cooperative Oncology Group (CECOG). J Clin Oncol, 2005 ASCO Annual Meeting Proceedings Part I of II, 2005, 23 (Suppl): 4010.

    Google Scholar 

  46. Cunningham D, Chau I, Stocken D, et al. Phase III randomized comparison of Gemcitabine (GEM) versus Gemcitabine plus Capecitabine (GEM-CAP) in patients with advanced pancreatic cancer. Eur J Cancer, 2005, 4(Suppl): PSII.

  47. Oettle H, Pelzer U, Stieler J, et al. Oxaliplatin/Folinic acid/5-Fluorouracil (24 h) plus best supportive care versus best supportive care alone (BSC) in second-line therapy of Gemcitabine-refractory advanced pancreatic cancer (CONKO 003). J Clin Oncol, 2005 ASCO Annual Meetings Proceedings Part I of II, 2005, 23(Suppl): 4031.

    Google Scholar 

  48. Demols A, Peeters M, Polus M, et al. Gemcitabine and Oxaliplatin (GEMOX) in Gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer, 2006, 94: 481–485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cantore M, Rabbi C, Fiorentini G, et al. Combined Irinotecan and Oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology, 2004, 67: 93–97.

    Article  CAS  PubMed  Google Scholar 

  50. Reni M, Pasetto L, Aprile G, et al. Ralitrexed-Eloxatin salvage chemotherapy in Gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer, 2006, 94: 785–791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus Gemcitabine compared to Gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). J Clin Oncol, 2005 ASCO Annual Meetings Proceedings Part I of II, 2005, 23(Suppl): 1.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Onkologie, Nationales Centrum für Tumorerkrankungen, Universitätsklinik Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany

    Anne Katrin Berger & Drik Jäger

Authors
  1. Anne Katrin Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Drik Jäger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Katrin Berger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berger, A.K., Jäger, D. Pancreatic cancer — Palliative therapy: chemotherapy. Chinese German J Clin Oncol 6, 142–148 (2007). https://doi.org/10.1007/s10330-007-0042-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10330-007-0042-3

Key words

Search

Navigation