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Gastroenterology Research and Practice
Volume 2012 (2012), Article ID 898931, 6 pages
http://dx.doi.org/10.1155/2012/898931
Review Article

Metastatic Pancreatic Cancer: Are We Making Progress in Treatment?

1University Department of Medicine, Queen Mary Hospital, Hong Kong
2University Department of Surgery, Queen Mary Hospital, New Clinical Building, 102 Pokfulam Road, Room 211B, Hong Kong
3Centre for Cancer Research, The University of Hong Kong, Hong Kong

Received 7 July 2012; Accepted 2 November 2012

Academic Editor: Marcus Bahra

Copyright © 2012 Joanne Chiu and Thomas Yau. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. Glimelius, K. Hoffman, P. O. Sjödén et al., “Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer,” Annals of Oncology, vol. 7, no. 6, pp. 593–600, 1996. View at Scopus
  2. H. A. Burris III, M. J. Moore, J. Andersen et al., “Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial,” Journal of Clinical Oncology, vol. 15, no. 6, pp. 2403–2413, 1997. View at Scopus
  3. T. Conroy, F. Desseigne, M. Ychou et al., “FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer,” The New England Journal of Medicine, vol. 364, no. 19, pp. 1817–1825, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. V. Heinemann, D. Quietzsch, F. Gieseler et al., “Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer,” Journal of Clinical Oncology, vol. 24, no. 24, pp. 3946–3952, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. E. Poplin, Y. Feng, J. Berlin et al., “Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern cooperative oncology group,” Journal of Clinical Oncology, vol. 27, no. 23, pp. 3778–3785, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. V. Heinemann, R. Labianca, A. Hinke, and C. Louvet, “Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study,” Annals of Oncology, vol. 18, no. 10, pp. 1652–1659, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. J. D. Berlin, P. Catalano, J. P. Thomas, J. W. Kugler, D. G. Haller, and A. B. Benson, “Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern cooperative oncology group trial E2297,” Journal of Clinical Oncology, vol. 20, no. 15, pp. 3270–3275, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Sultana, C. T. Smith, D. Cunningham, N. Starling, J. P. Neoptolemos, and P. Ghaneh, “Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses,” British Journal of Cancer, vol. 99, no. 1, pp. 6–13, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. D. Cunningham, I. Chau, D. D. Stocken et al., “Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer,” Journal of Clinical Oncology, vol. 27, no. 33, pp. 5513–5518, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Bernhard, D. Dietrich, W. Scheithauer et al., “Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial—SAKK 44/00-CECOG/PAN.1.3.001,” Journal of Clinical Oncology, vol. 26, no. 22, pp. 3695–3701, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Herrmann, G. Bodoky, T. Ruhstaller et al., “Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss group for clinical cancer research and the central European cooperative oncology group,” Journal of Clinical Oncology, vol. 25, no. 16, pp. 2212–2217, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. V. Heinemann, S. Boeck, A. Hinke, R. Labianca, and C. Louvet, “Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer,” BMC Cancer, vol. 8, article 82, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Sultana, C. T. Smith, D. Cunningham, N. Starling, J. P. Neoptolemos, and P. Ghaneh, “Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer,” Journal of Clinical Oncology, vol. 25, no. 18, pp. 2607–2615, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. V. Vaccaro, I. Sperduti, and M. Milella, “FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer,” The New England Journal of Medicine, vol. 365, no. 8, pp. 768–769, 2011. View at Publisher · View at Google Scholar
  15. C. Almoguera, D. Shibata, K. Forrester, J. Martin, N. Arnheim, and M. Perucho, “Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes,” Cell, vol. 53, no. 4, pp. 549–554, 1988. View at Scopus
  16. A. F. Hezel, A. C. Kimmelman, B. Z. Stanger, N. Bardeesy, and R. A. DePinho, “Genetics and biology of pancreatic ductal adenocarcinoma,” Genes and Development, vol. 20, no. 10, pp. 1218–1249, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Jones, X. Zhang, D. W. Parsons et al., “Core signaling pathways in human pancreatic cancers revealed by global genomic analyses,” Science, vol. 321, no. 5897, pp. 1801–1806, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. S. J. Cohen, L. Ho, S. Ranganathan et al., “Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma,” Journal of Clinical Oncology, vol. 21, no. 7, pp. 1301–1306, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. J. S. Macdonald, S. McCoy, R. P. Whitehead et al., “A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study,” Investigational New Drugs, vol. 23, no. 5, pp. 485–487, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. E. van Cutsem, H. van de Velde, P. Karasek et al., “Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer,” Journal of Clinical Oncology, vol. 22, no. 8, pp. 1430–1438, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. C. Lersch, E. van Cutsem, R. Amado, et al., “Randomized phase II study of SCH, 66336 and gemcitabine in the treatment of metastatic adenocarcinoma of the pancreas,” Proceedings—American Society of Clinical Oncology, vol. 20, abstract no. 608, 2001.
  22. K. Tobita, H. Kijima, S. Dowaki, et al., “Epidermal growth factor receptor expression in human pancreatic cancer: significance for liver metastasis,” International Journal of Molecular Medicine, vol. 11, no. 3, pp. 305–309, 2003.
  23. M. J. Moore, D. Goldstein, J. Hamm et al., “Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of Canada clinical trials group,” Journal of Clinical Oncology, vol. 25, no. 15, pp. 1960–1966, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Q. Xiong, A. Rosenberg, A. LoBuglio et al., “Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II trial,” Journal of Clinical Oncology, vol. 22, no. 13, pp. 2610–2616, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. P. A. Philip, J. Benedetti, C. L. Corless et al., “Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest oncology group-directed intergroup trial S0205,” Journal of Clinical Oncology, vol. 28, no. 22, pp. 3605–3610, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. G. P. Kim, N. R. Foster, M. Salim et al., “Randomized phase II trial of panitumumab, erlotinib, and gemcitabine (PGE) versus erlotinib-gemcitabine (GE) in patients with untreated, metastatic pancreatic adenocarcinoma,” Journal of Clinical Oncology, vol. 29, supplement, abstract no. 4030, 2011.
  27. Y. Seo, H. Baba, T. Fukuda, M. Takashima, and K. Sugimachi, “High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma,” Cancer, vol. 88, no. 10, pp. 2239–2245, 2000.
  28. H. L. Kindler, D. Niedzwiecki, D. Hollis et al., “Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the cancer and leukemia group B (CALGB 80303),” Journal of Clinical Oncology, vol. 28, no. 22, pp. 3617–3622, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. E. van Cutsem, W. L. Vervenne, J. Bennouna et al., “Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer,” Journal of Clinical Oncology, vol. 27, no. 13, pp. 2231–2237, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. H. L. Kindler, T. Ioka, D. J. Richel et al., “Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study,” The Lancet Oncology, vol. 12, no. 3, pp. 256–262, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Riess, et al., “Double-blind, placebo-controlled randomized phase III trial of aflibercept (A) plus gemcitabine (G) versus placebo (P) plus gemcitabine (G) in patients with metastatic pancreatic cancer: final results,” in Proceedings of the European Society for Medical Oncology's 12th World Congress on Gastrointestinal Cancer, Barcelona, Spain, 2010.
  32. A. Goncalves, M. Gilabert, E. François, et al., “BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer,” Annals of Oncology, vol. 23, no. 11, pp. 2799–2805, 2012. View at Publisher · View at Google Scholar
  33. M. Erkan, C. Reiser-Erkan, C. W. Michalski, and J. Kleeff, “Tumor microenvironment and progression of pancreatic cancer,” Experimental Oncology, vol. 32, no. 3, pp. 128–131, 2010. View at Scopus
  34. D. D. Von Hoff, R. K. Ramanathan, M. J. Borad, et al., “Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial,” Journal of Clinical Oncology, vol. 29, no. 34, pp. 4548–4554, 2011.
  35. U. Bergmann, H. Funatomi, M. Yokoyama, H. G. Beger, and M. Korc, “Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles,” Cancer Research, vol. 55, no. 10, pp. 2007–2011, 1995. View at Scopus
  36. J. W. Freeman, C. A. Mattingly, and W. E. Strodel, “Increased tumorigenicity in the human pancreatic cell line MIA PaCa-2 is associated with an aberrant regulation of an IGF-1 autocrine loop and lack of expression of the TGF-β type RII receptor,” Journal of Cellular Physiology, vol. 165, no. 1, pp. 155–163, 1995. View at Publisher · View at Google Scholar · View at Scopus
  37. B. A. Hanks, A. Holtzhausen, P. Gimpel, et al., “Effect of the loss of the type III TGFβ receptor during tumor progression on tumor microenvironment: preclinical development of TGFβ inhibition and TGFβ-related biomarkers to enhance immunotherapy efficacy,” Journal of Clinical Oncology, vol. 30, supplement, abstract no. 10563, 2012.
  38. H. S. Wasan, G. M. Springett, C. Chodkiewicz et al., “CA 19-9 as a biomarker in advanced pancreatic cancer patients randomised to gemcitabine plus axitinib or gemcitabine alone,” British Journal of Cancer, vol. 101, no. 7, pp. 1162–1167, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. J. García-Manteiga, M. Molina-Arcas, F. J. Casado, A. Mazo, and M. Pastor-Anglada, “Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2′,2′-difluorodeoxycytidine-induced cytotoxicity,” Clinical Cancer Research, vol. 9, no. 13, pp. 5000–5008, 2003. View at Scopus
  40. E. Giovannetti, M. del Tacca, V. Mey et al., “Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine,” Cancer Research, vol. 66, no. 7, pp. 3928–3935, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Nakano, S. Tanno, K. Koizumi et al., “Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells,” British Journal of Cancer, vol. 96, no. 3, pp. 457–463, 2007. View at Publisher · View at Google Scholar · View at Scopus