Adjuvant Therapy for Pancreatic Cancer

  • Asma Sultana
  • Trevor Cox
  • Paula Ghaneh
  • John P. NeoptolemosEmail author
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 196)


Pancreatic cancer is a challenging malignancy to treat, as less than one-fifth of diagnosed cases are resectable, surgery is complex and postoperative recovery slow, treated patients tend to relapse and overall survival rates are low. It is one of the leading causes of cancer-related mortality. Adjuvant therapy has been employed in resectable disease, to target micrometastases and improve prognosis. Chemotherapy, chemoradiotherapy (chemoRT) and chemoradiotherapy (chemoRT) followed on by chemotherapy have been evaluated in randomised controlled trials. The European Study Group for Pancreatic Cancer (ESPAC)-1 and CONKO-001 trials clearly established the survival advantage of adjuvant chemotherapy with 5 fluorouracil (5FU) plus folinic acid and gemcitabine respectively over no chemotherapy. The ESPAC-3 (version 2) trial demonstrated equivalence between 5FU plus folinic acid and gemcitabine in terms of survival parameters, though gemcitabine had a better toxicity profile. The results of these key studies, together with smaller ones have been subjected to meta-analyses, with confirmation of improved survival with adjuvant systemic chemotherapy. The EORTC-40891 and ESPAC-1 trials found no survival advantage with adjuvant chemoRT compared to observation, and this has been reflected in a subsequent meta-analysis. The popularisation of chemoRT, with follow on chemotherapy (versus observation) was based on the small underpowered GITSG trial. The ESPAC-1 trial was unable to find a survival benefit for chemoRT, with follow on chemotherapy compared to observation. The RTOG-9704 trial assessed chemoRT with follow on chemotherapy in both arms and found no difference between survival in the gemcitabine and 5FU arms. There has never been a published head-to-head randomised comparison of adjuvant chemotherapy to chemoRT, with follow on chemotherapy. Ongoing randomised trials are looking into adjuvant combination chemotherapy, chemotherapy with follow on chemoRT, and neoadjuvant therapy. Novel agents continue to be assessed in early phase trials with a major emphasis on predictive and prognostic biomarkers. Based on the available evidence, adjuvant chemotherapy with gemcitabine or 5FU/folinic acid is the current recommended gold standard in the management of resected pancreatic cancer.


Pancreatic Cancer Lymph Node Ratio Resectable Disease Regional Chemotherapy Periampullary Tumour 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





Confidence interval




External beam radiotherapy


Folinic acid


Gemcitabine + capecitabine



h ENT 1

Human equilibrative nucleoside transporter


Hazard ratio


Intraoperative radiotherapy


Individual patient data


Lymph node ratio


Cisplatin, epirubicin, capecitabine and gemcitabine


Randomised controlled trial


Recurrence-free survival




  1. Abrams R, Lillemoe K, Piantadosi S (2001) Continuing controversy over adjuvant therapy of pancreatic cancer. Lancet 358:1565PubMedCrossRefGoogle Scholar
  2. Abrams RA, Winter KA, Regine WF, Safran H, Hoffman JP, Lustig R, Konski AA, Benson AB, Macdonald JS, Rich TA, Willett CG (2012) Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704-A phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 82(2):809–816. doi: 10.1016/j.ijrobp.2010.11.039 PubMedCrossRefGoogle Scholar
  3. Andriulli A, Festa V, Botteri E, Valvano MR, Koch M, Bassi C, Maisonneuve P, Sebastiano PD (2011) Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. doi: 10.1245/s10434-011-2110-8 PubMedGoogle Scholar
  4. Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ (2011) Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery 150(3):466–473. doi: 10.1016/j.surg.2011.07.006 PubMedCrossRefGoogle Scholar
  5. Bakkevold K, Arnesjo B, Dahl O, Kambestad B (1993) 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 Can 29A(5):698–703CrossRefGoogle Scholar
  6. Bao PQ, Ramanathan RK, Krasinkas A, Bahary N, Lembersky BC, Bartlett DL, Hughes SJ, Lee KK, Moser AJ, Zeh HJ 3rd (2011) Phase II study of gemcitabine and erlotinib as adjuvant therapy for patients with resected pancreatic cancer. Ann Surg Oncol 18(4):1122–1129. doi: 10.1245/s10434-010-1401-9 PubMedCrossRefGoogle Scholar
  7. Bassi C, Stocken DD, Olah A, et al. (2005) The influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial. Digestive Surgery in pressGoogle Scholar
  8. Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, Konski A, Benson AB 3rd, MacDonald J, Willett CG (2008) Postresection CA 19–9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 26(36):5918–5922. doi: 10.1200/JCO.2008.18.6288 PubMedCrossRefGoogle Scholar
  9. Berlin J, Catalano PJ, Feng Y, Lowy AM, Blackstock AW, Philip PA, McWilliams RR, Abbruzzese JL, Benson AB (2010) ECOG 2204: an intergroup randomized phase II study of cetuximab (Ce) or bevacizumab (B) in combination with gemcitabine (G) and in combination with capecitabine (Ca) and radiation (XRT) as adjuvant therapy (Adj Tx) for patients (pts) with completely resected pancreatic adenocarcinoma (PC). J Clin Oncol 28[15 (May supplement)]:abstract 4034Google Scholar
  10. Boeck S, Ankerst DP, Heinemann V (2007) The role of adjuvant chemotherapy for patients with resected pancreatic cancer: systematic review of randomized controlled trials and meta-analysis. Oncology 72(5–6):314–321. doi: 10.1159/000113054 PubMedCrossRefGoogle Scholar
  11. Brunner TB, Grabenbauer GG, Meyer T, Golcher H, Sauer R, Hohenberger W (2007) Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomised phase II-study of the interdisciplinary working group gastrointestinal tumours (AIO, ARO, and CAO). BMC Cancer 7:41. doi: 10.1186/1471-2407-7-41 PubMedCrossRefGoogle Scholar
  12. Butturini G, Stocken DD, Wente MN, Jeekel H, Klinkenbijl JH, Bakkevold KE, Takada T, Amano H, Dervenis C, Bassi C, Buchler MW, Neoptolemos JP, Pancreatic Cancer Meta-Analysis G (2008) Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg 143(1):75–83, discussion 83. doi  10.1001/archsurg.2007.17 Google Scholar
  13. Chua YJ, Cunningham D (2005) Adjuvant treatment for resectable pancreatic cancer. J Clin Oncol 23(20):4532–4537PubMedCrossRefGoogle Scholar
  14. Coquard R, Ayzac L, Gilly F et al (1997) Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results. Radiother Oncol 44:271–275PubMedCrossRefGoogle Scholar
  15. Costello E, Neoptolemos JP (2011) Pancreatic cancer in 2010: new insights for early intervention and detection. Nat Rev Gastroenterol Hepatol 8(2):71–73. doi: 10.1038/nrgastro.2010.214 PubMedCrossRefGoogle Scholar
  16. Cunningham D, Chau I, Stocken D et al (2009) Phase III randomised comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27(33):5513–5518PubMedCrossRefGoogle Scholar
  17. Diener MK, Fitzmaurice C, Schwarzer G, Seiler CM, Antes G, Knaebel H, Büchler MW (2011) Pylorus-preserving pancreaticoduodenectomy (ppWhipple) versus pancreaticoduodenectomy (classicWhipple) for surgical treatment of periampullary and pancreatic carcinoma. In: Cochrane database of systematic reviewsedGoogle Scholar
  18. Doughlass H (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59:2006–2010CrossRefGoogle Scholar
  19. Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, Vauthey JN, Wang H, Cleary KR, Staerkel GA, Charnsangavej C, Lano EA, Ho L, Lenzi R, Abbruzzese JL, Wolff RA (2008) Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26(21):3496–3502. doi: 10.1200/JCO.2007.15.8634 PubMedCrossRefGoogle Scholar
  20. Farrell JJ, Elsaleh H, Garcia M, Lai R, Ammar A, Regine WF, Abrams R, Benson AB, Macdonald J, Cass CE, Dicker AP, Mackey JR (2009) Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology 136(1):187–195. doi: 10.1053/j.gastro.2008.09.067 PubMedCrossRefGoogle Scholar
  21. Fossati V, Cattaneo G, Zerbi A et al (1995) The role of intraoperative therapy by electron beam and combination of adjuvant chemotherapy and external radiotherapy in carcinoma of the pancreas. Tumori 81(1):23–31PubMedGoogle Scholar
  22. Garofalo M, Flannery T, Regine W (2006) The case for adjuvant chemoradiation for pancreatic cancer. Best Pract Res Clin Gastroenterol 20(2):403–416PubMedCrossRefGoogle Scholar
  23. Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS medicine 7(4):e1000267. doi: 10.1371/journal.pmed.1000267 PubMedCrossRefGoogle Scholar
  24. Hardacre JM, Mulcahy MF, Small Jr. W, Talamonti M, Obel JC, Rocha Lima CS, Safran H, Lenz H, Chiorean EG, Link CJ (2011) Effect of the addition of algenpantucel-L immunotherapy to standard adjuvant therapy on survival in patients with resected pancreas cancer. J Clin Oncol 29(supplement 4):abstract 236Google Scholar
  25. Hayashibe A, Kameyama M, Shinbo M, Makimoto S (2007) Clinical results on intra-arterial adjuvant chemotherapy for prevention of liver metastasis following curative resection of pancreatic cancer. Ann Surg Oncol 14(1):190–194. doi: 10.1245/s10434-006-9110-0 PubMedCrossRefGoogle Scholar
  26. Heinrich S, Schafer M, Weber A, Hany TF, Bhure U, Pestalozzi BC, Clavien PA (2008a) Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective phase II trial. Ann Surg 248(6):1014–1022. doi: 10.1097/SLA.0b013e318190a6da PubMedCrossRefGoogle Scholar
  27. Heinrich S, Pestalozzi BC, Schafer M, Weber A, Bauerfeind P, Knuth A, Clavien PA (2008b) Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26(15):2526–2531. doi: 10.1200/JCO.2007.15.5556 PubMedCrossRefGoogle Scholar
  28. Hiraoka T, Uchino R, Kanemitsu K et al (1990) Combination of intraoperative radiation with resection of cancer of the pancreas. Int J Pancreatol 7(1–3):201–207PubMedGoogle Scholar
  29. Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S (2006) Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg 10(4):511–518. doi: 10.1016/j.gassur.2005.09.016 PubMedCrossRefGoogle Scholar
  30. Jamieson NB, Carter CR, McKay CJ, Oien KA (2011) Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. Clin Cancer Res 17(10):3316–3331. doi: 10.1158/1078-0432.CCR-10-3284 PubMedCrossRefGoogle Scholar
  31. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60(5):277–300. doi: 10.3322/caac.20073 PubMedCrossRefGoogle Scholar
  32. Kalser M, Ellenberg S (1985) Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120:899–903PubMedCrossRefGoogle Scholar
  33. Klinkenbijl J, Jeekel J, Sahmoud T et al (1999) 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 230(6):776–784PubMedCrossRefGoogle Scholar
  34. Knaebel HP, Marten A, Schmidt J, Hoffmann K, Seiler C, Lindel K, Schmitz-Winnenthal H, Fritz S, Herrmann T, Goldschmidt H, Mansmann U, Debus J, Diehl V, Buchler MW (2005) 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 5(1):37PubMedCrossRefGoogle Scholar
  35. Koshy M, Landry J, Cavanaugh S et al (2005) A challenge to the therapeutic nihilism of ESPAC-1. Int J Radiat Oncol Biol Phys 61(4):965–966PubMedCrossRefGoogle Scholar
  36. Kosuge T, Kiuchi T, Mukai K, Kakizoe T (2006) A multicenter randomised controlled trial to evaluate the effect of adjuvant cisplatin and 5-Fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol 36(3):159–165PubMedCrossRefGoogle Scholar
  37. Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, Xu N, Cooper H, Benson AB 3rd (2010) Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol 101(7):587–592. doi: 10.1002/jso.21527 PubMedCrossRefGoogle Scholar
  38. Le Scodan R, Mornex F, Girard N, Mercier C, Valette PJ, Ychou M, Bibeau F, Roy P, Scoazec JY, Partensky C (2009) Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann Oncol 20(8):1387–1396. doi: 10.1093/annonc/mdp015 PubMedCrossRefGoogle Scholar
  39. Li D, Moughan J, Crane CH, Hoffman JP, Regine W, Abrams RA, Safran H, Freedman GM, Guha C, Abbruzzese JL (2011) Association of RecQ1 A159C polymorphism with overall survival of patients with resected pancreatic cancer: a replication study in RTOG 9704. J Clin Oncol 29(supplement 4):abstract 156Google Scholar
  40. Linehan DC, Tan MC, Strasberg SM, Drebin JA, Hawkins WG, Picus J, Myerson RJ, Malyapa RS, Hull M, Trinkaus K, Tan BR Jr (2008) Adjuvant interferon-based chemoradiation followed by gemcitabine for resected pancreatic adenocarcinoma: a single-institution phase II study. Ann Surg 248(2):145–151. doi: 10.1097/SLA.0b013e318181e4e9 PubMedCrossRefGoogle Scholar
  41. Maeda A, Boku N, Fukutomi A, Kondo S, Kinoshita T, Nagino M, Uesaka K (2008) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 in patients with resected pancreatic cancer: Japan adjuvant study group of pancreatic cancer (JASPAC-01). Jpn J Clin Oncol 38(3):227–229. doi: 10.1093/jjco/hym178 PubMedCrossRefGoogle Scholar
  42. Marechal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Young J, Salmon I, Deviere J, Van Laethem JL (2009) Human equilibrative nucleoside transporter 1 and human concentrative nucleoside transporter 3 predict survival after adjuvant gemcitabine therapy in resected pancreatic adenocarcinoma. Clin Cancer Res 15(8):2913–2919. doi: 10.1158/1078-0432.CCR-08-2080 PubMedCrossRefGoogle Scholar
  43. Marten A, Schmidt J, Ose J, Harig S, Abel U, Munter MW, Jager D, Friess H, Mayerle J, Adler G, Seufferlein T, Gress T, Schmid R, Buchler MW (2009) A randomized multicentre phase II trial comparing adjuvant therapy in patients with interferon alpha-2b and 5-FU alone or in combination with either external radiation treatment and cisplatin (CapRI) or radiation alone regarding event-free survival—CapRI-2. BMC Cancer 9:160. doi: 10.1186/1471-2407-9-160 PubMedCrossRefGoogle Scholar
  44. Marten A, Schmidt J, Debus J, Harig S, Lindel K, Klein J, Bartsch D, Capussotti L, Zülke C, Buchler M (2010) CapRI: final results of the open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon- 2b (CRI) versus 5-FU alone for patients with resected pancreatic adenocarcinoma (PAC). J Clin Oncol 28[18 (June 20 Supplement)]:LBA4012Google Scholar
  45. Michalski CW, Kleeff J, Wente MN, Diener MK, Buchler MW, Friess H (2007) Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg 94(3):265–273. doi: 10.1002/bjs.5716 PubMedCrossRefGoogle Scholar
  46. Michiels S, Piedbois P, Burdett S et al (2005) Meta-analysis when only the median survival times are known: a comparison with individual patient data results. Int J Technol Assess Health Care 21(1):119–125PubMedCrossRefGoogle Scholar
  47. Morak MJ, van der Gaast A, Incrocci L, van Dekken H, Hermans JJ, Jeekel J, Hop WC, Kazemier G, van Eijck CH (2008) Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial. Ann Surg 248(6):1031–1041. doi: 10.1097/SLA.0b013e318190c53e PubMedCrossRefGoogle Scholar
  48. Morak MJ, Pek CJ, Kompanje EJ, Hop WC, Kazemier G, van Eijck CH (2010) Quality of life after adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled study. Cancer 116(4):830–836. doi: 10.1002/cncr.24809 PubMedCrossRefGoogle Scholar
  49. Neoptolemos J, Dunn J, Stocken D et al (2001) Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358(9293):1576–1585PubMedCrossRefGoogle Scholar
  50. Neoptolemos J, Stocken D, Freiss H et al (2004) A randomised trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210PubMedCrossRefGoogle Scholar
  51. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Olah A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Buchler MW (2010) European study group for Pancreatic C. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304 (10):1073–1081. doi  10.1001/jama.2010.1275 Google Scholar
  52. Neuhaus P, Riess H, Post S, Gellert K, Ridwelski K, Schramm H, Zuelke C, Fahlke J, Langrehr J, Oettle H (2008) CONKO-001: final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer. J Clin Oncol 26 (15S):LBA4504, (May 20 Supplement)Google Scholar
  53. Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine versus observation in patients undergoing curative-intent resection of pancreatic cancer. A randomised controlled trial. JAMA 297(3):267–277PubMedCrossRefGoogle Scholar
  54. Office for National Statistics (2010) Cancer statistics registration: registration of cancers diagnosed in 2008, EnglandGoogle Scholar
  55. Office for National Statistics (2010) Mortality statistics: deaths registered in England and wales 2008Google Scholar
  56. Palmer DH, Stocken DD, Hewitt H, Markham CE, Hassan AB, Johnson PJ, Buckels JA, Bramhall SR (2007) A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol 14(7):2088–2096. doi: 10.1245/s10434-007-9384-x PubMedCrossRefGoogle Scholar
  57. Pérez-Mancera PA, Guerra C, Barbacid M, Tuveson DA (2012) What the mouse has told us about human pancreatic cancer. Gastroenterology in pressGoogle Scholar
  58. Picozzi V, Kozarek R, Traverso L (2003) Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 185:476–480PubMedCrossRefGoogle Scholar
  59. Picozzi VJ, Abrams RA, Decker PA, Traverso W, O’Reilly EM, Greeno E, Martin RC, Wilfong LS, Rothenberg ML, Posner MC, Pisters PW (2011) American college of surgeons oncology gmulticenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG Trial Z05031. Ann Oncol 22(2):348–354. doi: 10.1093/annonc/mdq384 PubMedCrossRefGoogle Scholar
  60. Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299(9):1019–1026. doi: 10.1001/jama.299.9.1019 PubMedCrossRefGoogle Scholar
  61. Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG (2011) Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol 18(5):1319–1326. doi: 10.1245/s10434-011-1630-6 PubMedCrossRefGoogle Scholar
  62. Reni M (2010) Neoadjuvant treatment for resectable pancreatic cancer: time for phase III testing? World J Gastroenterol 16(39):4883–4887PubMedCrossRefGoogle Scholar
  63. Reni M, Panucci M, Ferreri A et al (2001) Effect of local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50(3):651–658PubMedCrossRefGoogle Scholar
  64. Rizzato C, Campa D, Giese N, Werner J, Rachakonda PS, Kumar R, Schanne M, Greenhalf W, Costello E, Khaw KT, Key TJ, Siddiq A, Lorenzo-Bermejo J, Burwinkel B, Neoptolemos JP, Buchler MW, Hoheisel JD, Bauer A, Canzian F (2011) Pancreatic cancer susceptibility loci and their role in survival. PLoS ONE 6(11):e27921. doi: 10.1371/journal.pone.0027921 PubMedCrossRefGoogle Scholar
  65. Shore S, Raraty M, Ghaneh P, Neoptolemos J (2003) Chemotherapy for pancreatic cancer. Aliment Pharmacol Ther 18(11–12):1049–1069PubMedCrossRefGoogle Scholar
  66. Showalter TN, Winter KA, Berger AC, Regine WF, Abrams RA, Safran H, Hoffman JP, Benson AB, MacDonald JS, Willett CG (2011) The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: a secondary analysis of RTOG 9704. Int J Radiat Oncol Biol Phys 81(5):1328–1335. doi: 10.1016j.ijrobp.2010.07.1993 PubMedCrossRefGoogle Scholar
  67. Sindelar W, Kinsella T (1986) Randomised trial of intraoperative radiotherapy in resected carcinoma of the pancreas. Int J Radiat Oncol Biol Phys 12(suppl. 1):148CrossRefGoogle Scholar
  68. Smeenk HG, van Eijck CH, Hop WC, Erdmann J, Tran KC, Debois M, van Cutsem E, van Dekken H, Klinkenbijl JH, Jeekel J (2007) Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg 246(5):734–740. doi: 10.1097/SLA.0b013e318156eef3 PubMedCrossRefGoogle Scholar
  69. Smith RA, Tang J, Tudur-Smith C, Neoptolemos JP, Ghaneh P (2011) Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer. Br J Cancer 104(9):1440–1451. doi: 10.1038/bjc.2011.110 PubMedCrossRefGoogle Scholar
  70. Sperti C, Pasquali C, Piccoli A et al (1997) Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg 21:195–200PubMedCrossRefGoogle Scholar
  71. Stathis A, Moore M (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7:163–172PubMedCrossRefGoogle Scholar
  72. Stocken D, Buchler M, Dervenis C, et al. (2005) Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer, pp 1–10Google Scholar
  73. Sultana A, Tudur Smith C, Cunningham D, Starling N, Neoptolemos J, Ghaneh P (2007) Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 25(18):2607–2615PubMedCrossRefGoogle Scholar
  74. Takada T, Amano H, Yasuda H et al (2002) Is postoperative adjuvant chemotherapy useful for gall bladder carcinoma? A phase III multicentre prospective randomised controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95(8):1685–1695PubMedCrossRefGoogle Scholar
  75. Tempero M, Plunkett W, Ruiz Van Haperen V et al (2003) Randomised phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed-dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21(18):3383–3384CrossRefGoogle Scholar
  76. Turrini O, Ychou M, Moureau-Zabotto L, Rouanet P, Giovannini M, Moutardier V, Azria D, Delpero JR, Viret F (2010) Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: new neoadjuvant regimen was safe and provided an interesting pathologic response. Eur J Surg Oncol 36(10):987–992. doi: 10.1016/j.ejso.2010.07.003 PubMedCrossRefGoogle Scholar
  77. Tuveson D, Hanahan D (2011) Translational medicine: cancer lessons from mice to humans. Nature 471(7338):316–317. doi: 10.1038/471316a PubMedCrossRefGoogle Scholar
  78. Tuveson DA, Neoptolemos JP (2012) Understanding metastasis in pancreatic cancer: a call for new clinical approaches. Cell 148:1–4. doi: 10.1016/j.cell.2011.12.021 CrossRefGoogle Scholar
  79. Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, Doi R, Monden M, Hatori T, Tanaka M, Shimada M, Kanemitsu K (2009) A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese study group of adjuvant therapy for pancreatic cancer. Br J Cancer 101(6):908–915. doi  10.1038/sj.bjc.6605256 Google Scholar
  80. Van Laethem JL, Hammel P, Mornex F, Azria D, Van Tienhoven G, Vergauwe P, Peeters M, Polus M, Praet M, Mauer M, Collette L, Budach V, Lutz M, Van Cutsem E, Haustermans K (2010) Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. J Clin Oncol 28(29):4450–4456. doi: 10.1200/JCO.2010.30.3446 PubMedCrossRefGoogle Scholar
  81. Van Laethem JL, Verslype C, Iovanna JL, Michl P, Conroy T, Louvet C, Hammel P, Mitry E, Ducreux M, Maraculla T, Uhl W, Van Tienhoven G, Bachet JB, Marechal R, Hendlisz A, Bali M, Demetter P, Ulrich F, Aust D, Luttges J, Peeters M, Mauer M, Roth A, Neoptolemos JP, Lutz M (2011) New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. Ann Oncol. doi: 10.1093/annonc/mdr351 Google Scholar
  82. Varadhachary GR, Wolff RA, Crane CH, Sun CC, Lee JE, Pisters PW, Vauthey JN, Abdalla E, Wang H, Staerkel GA, Lee JH, Ross WA, Tamm EP, Bhosale PR, Krishnan S, Das P, Ho L, Xiong H, Abbruzzese JL, Evans DB (2008) Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26(21):3487–3495. doi: 10.1200/JCO.2007.15.8642 PubMedCrossRefGoogle Scholar
  83. Yoshitomi H, Togawa A, Kimura F, Ito H, Shimizu H, Yoshidome H, Otsuka M, Kato A, Nozawa S, Furukawa K, Miyazaki M, Pancreatic Cancer Chemotherapy Program of the Chiba University Department of General Surgery Affiliated Hospital G (2008) A randomized phase II trial of adjuvant chemotherapy with uracil/tegafur and gemcitabine versus gemcitabine alone in patients with resected pancreatic cancer. Cancer 113(9):2448–2456. doi  10.1002/cncr.23863 Google Scholar
  84. Zerbi A, Fossati V, Parolini D (1994) Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer. Cancer 73:2930–2935PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Asma Sultana
    • 1
  • Trevor Cox
    • 1
  • Paula Ghaneh
    • 1
  • John P. Neoptolemos
    • 1
    Email author
  1. 1.The Liverpool Cancer Research UK Trials Unit, and the Department of Molecular and Clinical Cancer Medicine CentreUniversity of Liverpool, Liverpool Cancer Research Centre, Royal Liverpool University HospitalLiverpoolUK

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