Adjuvant Chemoradiation for Pancreatic Cancer: Past, Present and Future

  • Michael C. Garofalo
  • William F. Regine
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)

Adjuvant chemoradiation began to be investigated for pancreatic cancer over three decades ago. During the intervening years we have achieved a better understanding of the molecular and genetic basis of pancreatic cancer; however the survival of patients treated with the best modern therapies has changed very little. According to data from the American Cancer Society, the 5-year survival for pancreatic cancer patients remains a dismal 5%, up from a historical 3% three decades ago (1). In 2007, an estimated 37,170 newly diagnosed cases of pancreatic cancer in the United States will be nearly equaled by an estimated 33,170 pancreatic cancer deaths (1). This underscores the continued need to develop novel multimodality treatment approaches to this disease. Surgery remains the cornerstone to any hope for long-term survival, however only approximately 10–20% of newly diagnosed patients present with nonmetastatic and potentially resectable disease (2). Pancreatic cancer is considered uniformly fatal in patients unable to undergo a resection. With respect to the minority of patients with resectable disease, cooperative groups both in the United States (US) and Europe have conducted randomized clinical trials in recent decades that have sought to define the potential benefit of adjuvant chemotherapy or adjuvant chemoradiotherapy versus surgery alone for patients with resectable disease. The results of these trials have been conflicting and as a consequence, no current standard exists with respect to adjuvant therapy. Gemcitabine appears to be the most promising agent based on recent phase III trials and may provide a foundation on which to build future trial designs (3, 4). Refinements in delivery techniques for continuous-course modern radiation therapy (RT) as well as promising targeted therapies may also improve upon historical outcomes when added to a gemcitabine backbone. The ideal time sequence of combined adjuvant therapies is also an area of active deliberation. Though there is no current standard for adjuvant therapy in pancreatic cancer, continued investigations into combinations of chemotherapy, radiation therapy, and biologic therapy are warranted. This chapter reviews the historical trials that have defined the potential benefits for adjuvant chemoradiation and examine ongoing and future trial concepts for adjuvant chemoradiation.


Pancreatic Cancer Radiat Oncol Biol Phys Intensity Modulate Radiation Therapy Radiation Therapy Oncology Group Resected Pancreatic Cancer 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jemal A, Siegel R, Ward E, et al. 2007 Cancer statistics, CA Cancer J Clin 2007. 57, 43–66,2007.CrossRefPubMedGoogle Scholar
  2. 2.
    Warshaw AL, Fernandex del-Castillo C. 1992, Pancreatic adenocarcinoma. N Engl J Med 326(7):455–465.PubMedCrossRefGoogle Scholar
  3. 3.
    Oettle H, Post S, Neuhaus P, 2007, Adjuvant chemotherapy with gemcitabine versus observation in patients undergoing curative-intent resection of pancreatic cancer. JAMA 297: 267–277.CrossRefPubMedGoogle Scholar
  4. 4.
    Regine WF, Winter KA, Abrams RA, 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.CrossRefPubMedGoogle Scholar
  5. 5.
    Griffin JF, Smalley SR, Jewell W, 1990, Patterns of failure after curative resection of pancreatic carcinoma. Cancer 66:56–61.CrossRefPubMedGoogle Scholar
  6. 6.
    Foo ML, Gunderson LL, Nagorney DM, 1993, Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation ± 5 fluorouracil. Int J Radiat Oncol Biol Phys 26: 483–489.PubMedGoogle Scholar
  7. 7.
    Tepper J, Nardi G, Suit H. 1973, Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy. Cancer 37(3):1519–1524.Google Scholar
  8. 8.
    Whittington R, Bryer MP, Haller DG, 1991, Adjuvant therapy of resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 21 (5): 1137–1143.PubMedGoogle Scholar
  9. 9.
    Hishinuma S, Ogata Y, Tomikawa M, 2006, Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg 10(4):511–518.CrossRefPubMedGoogle Scholar
  10. 10.
    Sperti C, Pasquali C, Piccoli A, 1997, Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg 21(2):195–200.CrossRefPubMedGoogle Scholar
  11. 11.
    Kayahara M, Nagakawa T, Ueno K, 1993, An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging. Cancer 72(7):2118–2123.CrossRefPubMedGoogle Scholar
  12. 12.
    Griffin JF, Smalley SR, Jewell W, 1990, Patterns of failure after curative resection of pancre-atic carcinoma. Cancer 66(1):56–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Macdonald JS, Smalley SR, Benedetti J, 2001, Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–230.CrossRefPubMedGoogle Scholar
  14. 14.
    Krook JE, Moertel CG, Gunderson LL, 1991, Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324:709–715.PubMedGoogle Scholar
  15. 15.
    Kalser MH, Ellenberg SS. 1985, Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120:899–903.PubMedGoogle Scholar
  16. 16.
    Douglass HO, Strablein DM. 1990, Ten year follow-up of first generation surgical adjuvant studies of the Gastrointestinal Tumor Study Group. In: Salmon SE (ed.) Adjuvant therapy of cancer, vol 4. WB Saunders, Philadelphia, 405–415.Google Scholar
  17. 17.
    Gastrointestinal Tumor Study Group. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 1987, 59:2006–2010.CrossRefGoogle Scholar
  18. 18.
    Klinkenbijl JH, Jeekel J, Sahmoud T, 1999, Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: a phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230(6):776–782.CrossRefPubMedGoogle Scholar
  19. 19.
    Garofalo MC, Regine WR, Tan MT. 2006, On statistical reanalysis, the EORTC trial is a positive trial for adjuvant chemoradiation in pancreatic cancer. Ann Surg 244 (2): 332–333.CrossRefPubMedGoogle Scholar
  20. 20.
    Neoptolemos JP, Dunn JA, Stocken DD, 2001, Adjuvant chemoradiotherapy and chemotherapy in respectable pancreatic cancer: a randomized controlled trial. Lancet 358:1576–1585.CrossRefPubMedGoogle Scholar
  21. 21.
    Neoptolemos JP, Stocken DD, Friess F, 2004, A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200–1210.CrossRefPubMedGoogle Scholar
  22. 22.
    Moertel CG, Childs DS Jr Reitemeier RJ, 1969, Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2:865–867.CrossRefPubMedGoogle Scholar
  23. 23.
    Hasalam JB, Cavenaugh PJ, Stroup SL. 1973, Radiation therapy in the treatment of irresecta-ble adenocarcinoma of the pancreas. Cancer 32:1341–1345.CrossRefGoogle Scholar
  24. 24.
    Choti MA. 2004, Adjuvant therapy for pancreatic cancer—the debate continues. N Engl J Med 350(12):1249–1251.CrossRefPubMedGoogle Scholar
  25. 25.
    Morris SL, Beasley M, Leslie M. 2004, Chemotherapy for pancreatic cancer. N Engl J Med 350(26):2713 [letter to the editor].CrossRefPubMedGoogle Scholar
  26. 26.
    Crane CH, Ben-Josef E, Small W. 2004, Chemotherapy for pancreatic cancer. N Engl J Med 350(26):2713–2714 [letter to the editor].CrossRefPubMedGoogle Scholar
  27. 27.
    Bydder S, Spry N. 2004, Chemotherapy for pancreatic cancer. N Engl J Med 350(26):2714 [letter to the editor].Google Scholar
  28. 28. ESPAC-3(v2): Phase III adjuvant trial in pancreatic cancer comparing 5FU and D-L-folinic acid versus gemcitabine. (Accessed 11/15/07 at aspx?TopicID=&StudyID=669 ).
  29. 29.
    Burris HA 3rd Moore MJ, Andersen J, 1997, Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15(6):2403–2413.PubMedGoogle Scholar
  30. 30.
    Abrams RA, Winter KA, Regine WF, 2006, Radiotherapy quality assurance review and survival. Proceedings of ASTRO, Int J Radiat Oncol Biol Phys 66 (3): S22.Google Scholar
  31. 31.
    Berger AC, Winter K, Hoffman J, et al. Post-resection CA 19-9 predicts overall survival (OS) in patients treated with adjuvant chemoradiation: A secondary endpoint of RTOG 9704. J Clin Oncol 2007, 25(18S):Abstract 4522.Google Scholar
  32. 32.
    Regine WF, Garcia M, Berger AC, 2007, Post-resectional CA 19-9 values <90 are associated with significantly worse survival in patients with pancreatic carcinoma treated with adjuvant therapy on RTOG 9704—implications for current and future trials. Int J Radiat Oncol Biol Phys 69 (3): S78; Abstract 137.Google Scholar
  33. 33.
    Sindelar WF, Kinsella T, Tepper J, 1983, Experimental and clinical studies with intraoperative radiotherapy. Surg Gynecol Obstet 157:205–219.PubMedGoogle Scholar
  34. 34.
    Zerbi A, Fossati V, Parolini D, 1994, Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer. Cancer 73:2930–2935.CrossRefPubMedGoogle Scholar
  35. 35.
    Kokubo M, Nishimura Y, Shibamoto Y, 2000, Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer. Int J Radiat Oncol Biol Phys 48:1081–1087.CrossRefPubMedGoogle Scholar
  36. 36.
    Sunamura M, Kobari M, Lozonschi L, 1998, Intraoperative radiotherapy for pancreatic adenocarcinoma. J Hepatobiliary Pancreat Surg 5:151–156.CrossRefPubMedGoogle Scholar
  37. 37.
    Coquard R, Ayzac L, Gilly FN, 1997, Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results. Radiother Oncol 44(3):271–275.CrossRefPubMedGoogle Scholar
  38. 38.
    Farrell TJ, Barbot DJ, Rosato FE. 1997, Pancreatic resection combined with intraoperative radiation therapy for pancreatic cancer. Ann Surg 226(1):66–69.CrossRefPubMedGoogle Scholar
  39. 39.
    Reni M, Panucci MG, Ferreri AJ, 2001, Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50: 651–658.PubMedGoogle Scholar
  40. 40.
    Landry JC, Yang GY, Ting JY, 2002, Treatment of pancreatic cancer tumors with intensity-modulated radiation therapy (IMRT) using the volume at risk approach (VARA): employing dose-volume histogram (DVH) and normal tissue complication probability (NTCP) to evaluate small bowel toxicity. Med Dosim 27(2):121–129.CrossRefPubMedGoogle Scholar
  41. 41.
    Bai YR, Wu GH, Guo WJ, 2003, Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer: results of feasibility study. World J Gastroenterol 9 (11):2561–2564.PubMedGoogle Scholar
  42. 42.
    Milano MT, Chmura SJ, Garofalo MC, 2004, Intensity modulated radiation therapy (IMRT) in the treatment of pancreatic and bile duct malignancies: toxicity and outcome. Int J Radiat Oncol Biol Phys 59 (2): 445–453.PubMedGoogle Scholar
  43. 43. EORTC-40013 (NCT00064207). Phase II/III randomized study of gemcitabine followed by chemoradiotherapy with gemcitabine versus gemcitabine alone after prior curative resection in patients with pancreatic head adenocarcinoma. (Accessed 11/15/07 at http://www.cancer. gov/clinicaltrials/EORTC-40013).

Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Michael C. Garofalo
    • 1
  • William F. Regine
    • 1
  1. 1.Radiation Oncology DepartmentUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations