Options for the Treatment of Gemcitabine-Resistant Advanced Pancreatic Cancer

  • Ioannis Gounaris Oncology Centre, Cambridge University Hospitals NHS Trust. Cambridge, United Kingdom
  • Kamarul Zaki Oncology Centre, Cambridge University Hospitals NHS Trust. Cambridge, United Kingdom
  • Pippa Corrie Oncology Centre, Cambridge University Hospitals NHS Trust. Cambridge, United Kingdom
Keywords: Drug Therapy, gemcitabine, Neoplasm Metastasis, Pancreatic Neoplasms


Context Pancreatic cancer is noteworthy in that the number of patients dying from the disease is roughly equal to the number diagnosed. For more than a decade, gemcitabine has constituted the standard of care for the palliative treatment of the majority of patients who present with metastatic or relapsed disease, although the survival gains are limited. Despite a median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit and these patients are candidates for second-line treatment. Methods The OVID MEDLINE database was searched from 1950 to present using the MeSH terms "pancreatic neoplasms", "drug treatment" and "gemcitabine". After excluding non-relevant results, 31 published studies were identified. These results were supplemented by searching the last three (2007-2009) American Society of Clinical Oncology (ASCO) Proceedings of Annual Meetings for studies published only in abstract form and reviewing reference lists of published articles. Results and discussion The evidence for second line treatments of metastatic pancreatic cancer consists mostly of single arm, small phase II studies. Oxaliplatin-fluoropyrimidine combinations appear promising and have shown increased survival compared to best supportive care. As the molecular pathways governing pancreatic cancer are unravelled, novel targeted therapies may offer the greatest promise for this disease either given alone, combined with one another, or with cytotoxic agents. The need for further, collaborative research is emphasised.

Image: The 80-metre high chimneys at Addenbrooke's Hospital. Cambridge, United Kingdom


Download data is not yet available.


National Cancer Institute. SEER Stat Fact Sheets. Surveillance Epidemiology and End Results (SEER). (FULL TEXT : http://seer.cancer.gov/statfacts/html/pancreas.html)

Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007; 18:581-92. [PMID 17287242] (FULL TEXT : http://annonc.oxfordjournals.org/cgi/content/full/18/3/581)

Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, 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; 15:2403-13. [PMID 9196156] (FULL TEXT : http://jco.ascopubs.org/cgi/reprint/15/6/2403.pdf)

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, 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. J Clin Oncol 2007; 25:1960-6. [PMID 17452677] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/25/15/1960)

Cunningham D, Chau I, Stocken D, et al. Phase III randomised comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEMCAP) in patients with advanced pancreatic cancer. Eur J Cancer 2005; 3(Suppl 4): Abstract PS11.

Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009; 27:5513-8. [PMID 19858379] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/27/33/5513)

Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 2009; 27:2231-7. [PMID 19307500] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/27/13/2231)

National Comprehensive Cancer Network. Pancreatic Adenocarcinoma V.1.2009. NCCN Clinical Practice Guidelines in Oncology. (FULL TEXT : http://www.nccn.org/professionals/physician_gls/PDF/pancreatic.pdf)

Pelzer U, Stieler J, Roll L, Hilbig A, Dörken B, Riess H, Oettle H. Second-line therapy in refractory pancreatic cancer. results of a phase II study. Onkologie 2009; 32:99-102. [PMID 19295247] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000197769)

Oettle H, Pelzer U, Stieler J, Hilbig a, Roll L, Schwaner I, et al. Oxaliplatin/folinic acid/5-fluorouracil [24h] (OFF) 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; 23:s4031. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/23/16_suppl/4031?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4031&searchid=1&FIRSTINDEX=0&volume=23&issue=16_suppl&resourcetype=HWCIT)

Pelzer U, Kubica K, Stieler J, Schwaner I, Heil G, Görner M, et al. A randomised trial in patients with gemcitabine-refractory pancreatic cancer. Final results of the CONKO 003 study. J Clin Oncol 2008; 26:s4508. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/4508?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4508&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Tsavaris N, Kosmas C, Skopelitis H, Gouveris P, Kopterides P, Loukeris D, et al. Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study. Invest New Drugs 2005; 23:369-75. [PMID 16012797] (FULL TEXT : http://www.springerlink.com/content/q9125u415347r742/fulltext.pdf)

Novarino A, Satolli MA, Chiappino I, Giacobino A, Bellone G, Rahimi F, et al. Oxaliplatin, 5-fluorouracil, and leucovorin as second-line treatment for advanced pancreatic cancer. Am J Clin Oncol 2009; 32:44-8. [PMID 19194124] (FULL TEXT : http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2009&issue=02000&article=00010&type=abstract)

Gebbia V, Maiello E, Giuliani F, Borsellino N, Caruso M, Di Maggio G, et al. Second-line chemotherapy in advanced pancreatic carcinoma: a multicenter survey of the Gruppo Oncologico Italia Meridionale on the activity and safety of the FOLFOX4 regimen in clinical practice. Ann Oncol 2007; 18(Suppl vi):124-7. [PMID 17591805] (FULL TEXT : http://annonc.oxfordjournals.org/cgi/reprint/18/suppl_6/vi124.pdf)

Hwang J, Yoo C, Kim T, Lee J, Park D, Seo D, et al. A randomised phase II trial of FOLFOX or FOLFIRI.3 as second-line therapy in patients with advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy. J Clin Oncol 2009; 27:s4618. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/4618?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4618&searchid=1&FIRSTINDEX=0&volume=27&issue=15S&resourcetype=HWCIT)

Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer 2008; 113:2046-52. [PMID 18756532] (FULL TEXT : http://www3.interscience.wiley.com/cgi-bin/fulltext/121391199/HTMLSTART)

Gasent-Blesa J, Alberola-Candel V, Giner-Marco V, Juan O, Provencio Pulla M, Llorca C, Gravalos C. Phase II trial of second-line chemotherapy in metastatic pancreas cancer with the combination of oxaliplatin (Ox) and capecitabine (Cp). J Clin Oncol 2009; 27:e15561. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/e15561)

Sancho A, Lopez-Vivanco G, Diaz de Corcuera I, Ferreiro J, Moreno A, Mielgo X, et al. Oxaliplatin and capecitabine after gemcitabine failure in patients with advanced pancreatic, biliary or gallbladder adenocarcinoma (APBC). J Clin Oncol 2008; 26:s15625. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/15625?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=15625&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Androulakis N, Syrigos K, Polyzos A, Aravantinos G, Stathopoulos GP, Ziras N, et al. Oxaliplatin for pretreated patients with advanced or metastatic pancreatic cancer: a multicenter phase II study. Cancer Invest 2005; 23:9-12. [PMID 15779862] (FULL TEXT : http://informahealthcare.com/doi/full/10.1081/CNV-46502)

Veltkamp S, Beijnen JH, Schellens J. Prolonged versus standard gemcitabine infusion: translation of molecular pharmacology to new treatment strategy. Oncologist 2008; 13;261-76. [PMID 18378536] (FULL TEXT : http://theoncologist.alphamedpress.org/cgi/content/full/13/3/261)

Demols A, Peeters M, Polus M, Marechal R, Gay F, Monsaert E, et al. Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer 2006; 94:481-5. [PMID 16434988] (FULL TEXT : http://www.nature.com/bjc/journal/v94/n4/full/6602966a.html)

Fortune BE, Li X, Kosuri KV, Weatherby LM, Thomas JP, Bekaii-Saab TS. Fixed-dose-rate gemcitabine in combination with oxaliplatin in patients with metastatic pancreatic cancer refractory to standard-dose-rate gemcitabine: a single-institute study. Oncology 2009; 76:333-7. [PMID 19307739] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000209962)

Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, 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. J Clin Oncol 2009; 27:3778-85. [PMID 19581537] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/27/23/3778)

Cantore M, Rabbi C, Fiorentini G, Oliani C, Zamagni D, Iacono C, et al. Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology 2004; 67:93-7. [PMID 15539911] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=OCL2004067002093)

Mazzer M, Zanon E, Foltran L, De Pauli F, Cardellino G, Iaiza E, et al. Second-line pemetrexed-oxaliplatin combination for advanced pancreatic adenocarcinoma. J Clin Oncol 2009; 27:e15597. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/e15597)

Reni M, Pasetto L, Aprile G, Cordio S, Bonetto E, Dell'Oro S, et al. Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer 2006; 94:785-91. [PMID 16508631] (FULL TEXT : http://www.nature.com/bjc/journal/v94/n6/full/6603026a.html)

Morizane C, Okusaka T, Furuse J, Ishii H, Ueno H, Ikeda M, et al. A phase II study of S-1 in gemcitabine-refractory metastatic pancreatic cancer. Cancer Chemother Pharmacol 2009; 63:313-9. [PMID 18398614] (FULL TEXT : http://www.springerlink.com/content/p14003h021w45138/fulltext.html)

Nakai Y, Isayama T, Sasaki T, Sasahira N, Hirano K, Tsujino T, et al. The role of S-1 in gemcitabine-refractory pancreatic cancer: a retrospective single-institution study. J Clin Oncol 2009; 27:e15648. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/e15648)

Boeck S, Wilkowski R, Bruns CJ, Issels RD, Schulz C, Moosmann N, et al. Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer. Oncology 2007; 73:221-7. [PMID 18424886] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000127413)

Togawa A, Yoshitomi H, Ito H, Kimura F, Shimizu H, Ohtsuka M, et al. Treatment with an oral fluoropyrimidine, S-1, plus cisplatin in patients who failed postoperative gemcitabine treatment for pancreatic cancer: a pilot study. Int J Clin Oncol 2007; 12:268-73. [PMID 17701005] (FULL TEXT : http://www.springerlink.com/content/v350v20072m8xh63/fulltext.pdf)

Reni M, Cereda S, Mazza E, Passoni P, Nicoletti R, Balzano G, et al. PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after gemcitabine-containing chemotherapy. Am J Clin Oncol 2008; 31:145-50. [PMID 18391598] (FULL TEXT : http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2008&issue=04000&article=00006&type=abstract)

Kozuch P, Grossbard ML, Barzdins A, Araneo M, Robin A, Frager D, et al. Irinotecan combined with gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (G-FLIP) is an effective and noncrossresistant treatment for chemotherapy refractory metastatic pancreatic cancer. Oncologist 2001; 6:488-95. [PMID 11743211] (FULL TEXT : http://theoncologist.alphamedpress.org/cgi/content/full/6/6/488)

Kim YJ, Bang S, Park JY, Park SW, Chung JB, Song SY. Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. Cancer Chemother Pharmacol 2009; 63:529-33. [PMID 18766341] (FULL TEXT : http://www.springerlink.com/content/l006x807j4125344/fulltext.html)

Lee S, Oh S, Kim B, Kwon H, Kim S, Rho M, et al. Second-line treatment with a combination of 5-fluorouracil, adriamycin, and mitomycin-C (FAM) in gemcitabine-pretreated pancreatic and biliary tract cancer. J Clin Oncol 2008; 26:s15606. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/15606?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=15606&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Blaya M, Lopes GL, Roman E, Ahn E, Macintyre J, Quesada J, et al. Phase II trial of capecitabine and docetaxel as second line therapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 2007; 25:s15029. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/25/18_suppl/15029?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=15029&searchid=1&FIRSTINDEX=0&volume=25&issue=18_suppl&resourcetype=HWCIT)

Bergmann F, Breinig M, Höpfner M, Rieker RJ, Fischer L, Köhler C, et al. Expression pattern and functional relevance of epidermal growth factor receptor and cyclooxygenase-2: novel chemotherapeutic targets in pancreatic endocrine tumors? Am J Gastroenterol 2009; 104:171-81. [PMID 19098866] (FULL TEXT : http://www.nature.com/ajg/journal/v104/n1/full/ajg200833a.html)

Milella M, Gelibter A, Di Cosimo S, Bria E, Ruggeri EM, Carlini P, et al. Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma. Cancer 2004; 101:133-8. [PMID 15221998] (FULL TEXT : http://www3.interscience.wiley.com/cgi-bin/fulltext/108566034/HTMLSTART)

Pino MS, Milella M, Gelibter A, Sperduti I, De Marco S, Nuzzo C, et al. Capecitabine and celecoxib as second-line treatment of advanced pancreatic and biliary tract cancers. Oncology 2009; 76:254-61. [PMID 19246950] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000205388)

Saif MW, Li J, Lamb L, Rosenberg A, Elligers K, Ruta S, et al. A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC). J Clin Oncol 2009; 27:e15508. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/e15508)

Yi SY, Park YS, Kim HS, Jun HJ, Kim KH, Chang MH, et al. Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer. Cancer Chemother Pharmacol 2009; 63:1141-5. [PMID 18839175] (FULL TEXT : http://www.springerlink.com/content/0q3p416g83003058/fulltext.html)

Ko AH, Dito E, Schillinger B, Venook AP, Bergsland EK, Tempero MA. Excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer: results of a phase II study. Cancer Invest 2008; 26:47-52. [PMID 18181045] (FULL TEXT : http://informahealthcare.com/doi/pdf/10.1080/07357900701681483)

Reni M, Panucci MG, Passoni P, Bonetto E, Nicoletti R, Ronzoni M, et al. Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: a phase I and II trial. Cancer Invest 2004; 22:688-96. [PMID 15581049] (FULL TEXT : http://informahealthcare.com/doi/full/10.1081/CNV-200032929)

Ulrich-Pur H, Raderer M, Verena Kornek G, Schüll B, Schmid K, Haider K, et al. Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 2003; 88:1180-4. [PMID 12698181] (FULL TEXT : http://www.nature.com/bjc/journal/v88/n8/full/6600883a.html)

Burris HA 3rd, Rivkin S, Reynolds R, Harris J, Wax A, Gerstein H, et al. Phase II trial of oral rubitecan in previously treated pancreatic cancer patients. Oncologist 2005; 10:183-90. [PMID 15793221] (FULL TEXT : http://theoncologist.alphamedpress.org/cgi/content/full/10/3/183)

Jacobs AD, Burris HA, Rivkin S, Ritch PS, Eisenberg PD, Mettinger KL. A randomized phase III study of rubitecan (ORA) vs. best choice (BC) in 409 patients with refractory pancreatic cancer report from a North-American multi-center study. J Clin Oncol 2004; 22:s4013. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/22/14_suppl/4013?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=A+randomized+phase+III+study+of+rubitecan&searchid=1&FIRSTINDEX=0&volume=22&issue=14_suppl&resourcetype=HWCIT)

Cereda S, Reni M. Weekly docetaxel as salvage therapy in patients with gemcitabine-refractory metastatic pancreatic cancer. J Chemother 2008; 20:509-12. [PMID 18676234] (FULL TEXT : http://www.jchemother.it/cgi-bin/digisuite.exe/product?ID=1806&IDCategory=141)

Carvajal RD, Shah MA, Tse A, Lefkowitz R, Kelsen DP, Schwartz GK, O'Reilly EM. A phase II study of docetaxel (D) followed by flavopiridol (F) in advanced, gemcitabine-refractory pancreatic cancer (PC). J Clin Oncol 2008; 26:s15558. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/15558?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=15558&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Oettle H, Arnold D, Esser M, Huhn D, Riess H. Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma. Anticancer Drugs 2000; 11:635-8. [PMID 11081455] (FULL TEXT : http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2000&issue=09000&article=00006&type=abstract)

Boeck S, Weigang-Köhler K, Fuchs M, Kettner E, Quietzsch D, Trojan J, et al. Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial. Ann Oncol 2007; 18:745-51. [PMID 17229775] (FULL TEXT : http://annonc.oxfordjournals.org/cgi/content/full/18/4/745)

Moore MJ, Tang P, Renouf D, Major P, Hedley D, Paterson V, et al. A phase II study of halichondrin B analog eribulin mesylate (E7389) as second-line therapy for patients with advanced pancreatic cancer. J Clin Oncol 2009; 27:e15634. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/e15634)

Stathopoulos GP, Boulikas T, Vougiouka M, Rigatos SK, Stathopoulos JG. Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study. Oncol Rep 2006; 15:1201-4. [PMID 16596187] (FULL TEXT : http://www.spandidos-publications.com/serveFile/or_15_5_1201_PDF.pdf?type=article&article_id=or_15_5_1201&item=PDF)

Tschoep KE, Boeck S, Berger F, Maier V, Abdel-Rahman S, Kuhlencordt M, et al. Regional hyperthermia (RHT) combined with gemcitabine (GEM) + cisplatin (CIS) in patients with GEM-refractory advanced pancreatic cancer: Results of the ESHO phase II trial. J Clin Oncol 2008; 26:s4635. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/4635?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4635&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Burris H 3rd, Rocha-Lima C. New therapeutic directions for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways. Oncologist 2008; 13:289-98. [PMID 18378539] (FULL TEXT : http://theoncologist.alphamedpress.org/cgi/content/full/13/3/289)

Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988; 53:549-54. [PMID 2453289] (FULL TEXT : http://download.cell.com/pdf/PII0092867488905715.pdf)

Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004; 22:1430-8. [PMID 15084616] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/22/8/1430)

Morton JP, Lewis BC. Shh signaling and pancreatic cancer: implications for therapy? Cell Cycle 2007; 6:1553-7. [PMID 17611415] (FULL TEXT : http://www.landesbioscience.com/journals/cc/mortonCC6-13.pdf)

Mysliviec P, Boucher MJ. Targeting Notch signaling in pancreatic cancer patients--rationale for new therapy. Adv Med Sci 2009; 54:136-42. [PMID 19758972] (FULL TEXT : http://versita.metapress.com/content/308m6x3278103702/fulltext.pdf)

Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol 2007; 25:4787-92. [PMID 17947726] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/25/30/4787)

Javle MM, Xiong H, Reddy S, Bhosale P, Davis D, Varadhachary G, et al. Inhibition of mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: The results of two prospective phase II studies. J Clin Oncol 2009; 27:s4621. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/4621?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4621&searchid=1&FIRSTINDEX=0&volume=27&issue=15S&resourcetype=HWCIT)

Ko AH, Dito E, Schillinger B, Venook AP, Bergsland EK, Korn WM, Tempero MA. A phase II study of bevacizumab (BEV) plus erlotinib (ERL) in patients with gemcitabine (GEM)-refractory metastatic pancreatic cancer (MPC). J Clin Oncol 2008; 26:s4516. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/4516?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4516&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Li J, Kleeff J, Giese N, Büchler MW, Korc M, Friess H. Gefitinib ('Iressa', ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits pancreatic cancer cell growth, invasion, and colony formation. Int J Oncol 2004; 25:203-10. [PMID 15202007]

Ignatiadis M, Polyzos A, Stathopoulos GP, Tselepatiotis E, Christophylakis C, Kalbakis K, et al. A multicenter phase II study of docetaxel in combination with gefitinib in gemcitabine-pretreated patients with advanced/metastatic pancreatic cancer. Oncology 2006; 71:159-63. [PMID 17646699] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000106064)

Brell JM, Matin K, Evans T, Volkin RL, Kiefer GJ, Schlesselman JJ, et al. Phase II study of docetaxel and gefitinib as second-line therapy in gemcitabine pretreated patients with advanced pancreatic cancer. Oncology 2009; 76:270-4. [PMID 19258727] (FULL TEXT : http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000206141)

Astsaturov IA, Meropol NJ, Alpaugh RK, Cheng JD, Lewis L, Beard M, et al. A randomized phase II and coagulation study of bevacizumab alone or with docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma. J Clin Oncol 2007; 25:s4556. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/25/18_suppl/4556?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4556&searchid=1&FIRSTINDEX=0&volume=25&issue=18_suppl&resourcetype=HWCIT)

Dragovich T, Laheru DA, Crowley JJ, Smith LS, Seng J, Burris HA III, et al. Phase II trial of vatalinib in patients with advanced or metastatic pancreatic adenocarcinoma who failed gemcitabine therapy. J Clin Oncol 2008; 26:s4615. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/4615?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4615&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

O' Reilly EM, Niedzwiecki D, Hollis DR, Bekaii-Saab TS, Pluard T, Duffy A, et al. A phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603. J Clin Oncol 2008; 26:s4515. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/26/15_suppl/4515?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4515&searchid=1&FIRSTINDEX=0&volume=26&issue=15_suppl&resourcetype=HWCIT)

Garrido-Laguna I, Rudek M, Tan A, Uson M, Iacobuzio-Donahue C, Angenendt M, et al. Preclinical identification of biomarkers of response to mTOR inhibitors and subsequent application in a phase II trial of sirolimus in pancreatic cancer patients refractory to gemcitabine. J Clin Oncol 2009; 27:s4612. (FULL TEXT : http://meeting.ascopubs.org/cgi/content/abstract/27/15S/4612?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=4612&searchid=1&FIRSTINDEX=0&volume=27&issue=15S&resourcetype=HWCIT)

Wolpin BM, Hezel AF, Abrams T, Blaszkowsky LS, Meyerhardt JA, Chan JA, et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009; 27:193-8. [PMID 19047305] (FULL TEXT : http://jco.ascopubs.org/cgi/content/full/27/2/193)

Nakachi K, Furuse J, Ishii H, Suzuki E, Yoshino M. Prognostic factors in patients with gemcitabine-refractory pancreatic cancer. Jpn J Clin Oncol 2007; 37:114-20. [PMID 17272317] (FULL TEXT : http://jjco.oxfordjournals.org/cgi/content/full/37/2/114

Image: The 80-metre high chimneys at Addenbrooke's Hospital
How to Cite
GounarisI., ZakiK., & CorrieP. (2010). Options for the Treatment of Gemcitabine-Resistant Advanced Pancreatic Cancer. JOP. Journal of the Pancreas, 11(2), 113-123. https://doi.org/10.6092/1590-8577/3842