Novel Chemoradiation in Localized Pancreatic Cancer: Clinical Studies

  • Christopher H. Crane
  • Gauri Varadhachary
  • Peter W. T. Pisters
  • Douglas B. Evans
  • Robert A. Wolff
Part of the Medical Radiology book series (MEDRAD)

15.9 Conclusion

Improving the treatment of pancreatic cancer is a challenge. Whenever possible, patients should be enrolled in investigational studies that evaluate novel therapies. Outside of a clinical trial, postoperative chemoradiation is the current standard adjuvant treatment after pancreaticoduodenectomy in the United States, but results from all randomized trials indicate significant rates of local tumor recurrence. For locally advanced disease, improving local tumor control rates is an important goal as well. In both cases, patients probably benefit from gemcitabine-based chemotherapy as well as chemoradiation. A strategy that incorporates both probably takes advantage of the best-available established therapies. The incorporation of molecularly targeted therapy with well-tolerated chemoradiation and chemotherapy regimens is a promising approach that addresses the limitations of conventional therapy without introducing unacceptable toxicity. Fortunately, investigators have placed more emphasis on pancreatic cancer in recent years than in the past, and many more clinical trials evaluating novel radiosensitizers are available to patients. Enrollment of patients in these studies is critical to the improvement of outcome in this disease.


Pancreatic Cancer Clin Oncol Radiat Oncol Biol Phys Advanced Pancreatic Cancer Local Tumor Control 
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.


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  1. American Joint Committee on Cancer (2002) Exocrine pancreas. In: FL Greene, DL Page, ID Fleming et al. (eds) AJCC Cancer Staging Manual. Springer-Verlag, Berlin Heidelberg New York, pp 157–164Google Scholar
  2. Anonymous (1979) A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group. Ann Surg 189:205–208Google Scholar
  3. Anonymous (1985) Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer 56:2563–2568CrossRefGoogle Scholar
  4. Anonymous (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59:2006–2010CrossRefGoogle Scholar
  5. Anonymous (1988) Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Inst 80:751–755Google Scholar
  6. Bajetta E, Di Bartolomeo M et al. (1999) Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. Int J Radiat Oncol Biol Phys 45:285–289APubMedCrossRefGoogle Scholar
  7. Balter J M, Lam KL et al. (1998) Improvement of CT-based treatment-planning models of abdominal targets using static exhale imaging. Int J Radiat Oncol Biol Phys 41:939–943PubMedCrossRefGoogle Scholar
  8. Blackstock AW, Bernard SA et al. (1999) Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol 17:2208–2212PubMedGoogle Scholar
  9. Blackstock A, Tempero M et al. (2001) Cancer and Leukemia Group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with localoregional adenocarcinoma of the pancreas (Abstract). Int J Radiat Oncol Biol Phys 51[Suppl]:31CrossRefGoogle Scholar
  10. Bonner JA, Harari PM et al. (2004) Cetuximab prolongs survival in patients with locoregionally advanced aquamous cell carcinoma of head and neck: A phase III study of high dose radiation therapy with or without Cetuximab. J Clin Oncol 23[Suppl]:5507 (abstract)Google Scholar
  11. Breslin TM, Hess KR et al. (2001) Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 8:123–132PubMedGoogle Scholar
  12. Brunner T, Grabenbauer G et al. (2000) A phase I trial of simultaneous gemcitabine/cisplatin and radiotherapy for patients with locally advanced pancreatic cancer. Proc Am Soc Clin Oncol 19:1109 (abstract)Google Scholar
  13. Burris H A 3rd, Moore MJ et al. (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 15:2403–2413PubMedGoogle Scholar
  14. Bussels B, Goethals L et al. (2003) Respiration-induced movement of the upper abdominal organs: a pitfall for the threedimensional conformal radiation treatment of pancreatic cancer. Radiother Oncol 68:69–74PubMedCrossRefGoogle Scholar
  15. Cartwright TH, Cohn A et al. (2002) Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol 20:160–164PubMedCrossRefGoogle Scholar
  16. Cassidy J, Scheithauer W et al. (2004) Capecitabine (X) vs bolus 5-FU/leucovorin (LV) as adjuvant therapy for colon cancer (the X-ACT study): efficacy results of a phase III trial. J Clin Oncol 23[Suppl]:3509 (abstract)Google Scholar
  17. Crane CH, Antolak JA et al. (2001a) Phase I study of concomitant gemcitabine and IMRT for patients with unresectable adenocarcinoma of the pancreatic head. Int J Gastrointest Cancer 30:123–132PubMedCrossRefGoogle Scholar
  18. Crane CH, Janjan NA et al. (2001b) Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer. Int J Pancreatol 29:9–18PubMedGoogle Scholar
  19. Crane CH, Wolff RA et al. (2001c) Combining gemcitabine with radiation in pancreatic cancer: understanding important variables influencing the therapeutic index. Semin Oncol 28[3 Suppl 10]:25–33PubMedCrossRefGoogle Scholar
  20. Crane CH, Abbruzzese JL et al. (2002) Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer? Int J Radiat Oncol Biol Phys 52:1293–1302PubMedCrossRefGoogle Scholar
  21. Crane C, Ellis L et al. (2006) Phase I trial of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic adenocarcinoma. J Clin Oncol, in pressGoogle Scholar
  22. DiPetrillo T, Baker R et al. (2000) Paclitaxel and concurrent radiation for locally advanced pancreatic cancer (abstract). Proc Am Soc Clin Oncol 19:294aGoogle Scholar
  23. Dobelbower RR, Bronn DG (1990) Radiotherapy in the treatment of pancreatic cancer. Baillieres Clin Gastroenterol 4:969–983PubMedCrossRefGoogle Scholar
  24. Epelbaum R, Rosenblatt E et al. (2000) Phase II study of gemcitabine combined with radiation therapy in localized, unresectable pancreatic cancer. Proc Am Soc Clin Oncol 19:1029 (abstract)Google Scholar
  25. Evans DB, Rich TA et al. (1992) Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 127:1335–1339PubMedGoogle Scholar
  26. Gorski DH, Beckett MA et al. (1999) Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 59:3374–3378PubMedGoogle Scholar
  27. Iannitti DM, Dipetrillo TM et al. (2005) Erlotinib and chemoradiation followed by maintenance erlotinib for locally advanced pancreatic cancer: a phase I study. Am J Clin Oncol 28:570–575PubMedCrossRefGoogle Scholar
  28. Ishii H, Okada S et al. (1997) Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. Cancer 79:1516–1520PubMedCrossRefGoogle Scholar
  29. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62PubMedCrossRefGoogle Scholar
  30. Jeekel J, Treurniet-Donker AD (1991) Treatment perspectives in locally advanced unresectable pancreatic cancer. Br J Surg 78:1332–1334PubMedGoogle Scholar
  31. Jessup JM, Steele G Jr. et al. (1993) Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg 128:559–564PubMedGoogle Scholar
  32. Kamthan AG, Morris JC et al. (1997) Combined modality therapy for stage II and stage III pancreatic carcinoma. J Clin Oncol 15:2920–2927PubMedGoogle Scholar
  33. Kapiteijn E, Marijnen CA et al. (2001) Preoperative radiotherapy combined with total mesorectal excision for respectable rectal cancer. N Engl J Med 345:638–646PubMedCrossRefGoogle Scholar
  34. Klaassen DJ, MacIntyre JM et al. (1985) Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil — an Eastern Cooperative Oncology Group study. J Clin Oncol 3:373–378PubMedGoogle Scholar
  35. Klinkenbijl JH, Jeekel J 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 230:776–782PubMedCrossRefGoogle Scholar
  36. Koong AC, Le QT et al. (2004) Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 58:1017–1021PubMedCrossRefGoogle Scholar
  37. Kornek GV, Schratter-Sehn A et al. (2000) Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin. Br J Cancer 82:98–103PubMedCrossRefGoogle Scholar
  38. Krook JE, Moertel CG et al. (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324:709–715PubMedCrossRefGoogle Scholar
  39. Li CP, Chao Y et al. (2003) Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: Gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys 57:98–104PubMedCrossRefGoogle Scholar
  40. Macdonald JS, Smalley SR et al. (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730PubMedCrossRefGoogle Scholar
  41. McGinn CJ, Shureiqi I et al. (2000) Surgical resection following concurrent gemcitabine/radiation therapy in patients with previously unresectable pancreatic cancer (abstract). Radiother Oncol 56:S57Google Scholar
  42. McGinn CJ, Zalupski MM et al. (2001) Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 19:4202–4208PubMedGoogle Scholar
  43. McGinn C, Talamonti M et al. (2004) A phase II trial of fulldose gemcitabine with concurrent radiation therapy in patients with resectable or unresectable non-metastatic pancreatic cancer (abstract). Proc Am Soc Clin Oncol GI Symposium: 89Google Scholar
  44. Moertel CG, Frytak S et al. (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48:1705–1710PubMedCrossRefGoogle Scholar
  45. Neoptolemos JP, Stocken DD et al. (2001) Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg 234:758–768PubMedCrossRefGoogle Scholar
  46. Neoptolemos JP, Stocken DD et al. (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210PubMedCrossRefGoogle Scholar
  47. Pipas JM, Mitchell SE et al. (2001) Phase I study of twiceweekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 50:1317–1322PubMedCrossRefGoogle Scholar
  48. Pisters PWT, Abbruzzese JL et al. (1998) Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol 16:3843–3850PubMedGoogle Scholar
  49. Pisters PWT, Wolff RA et al. (2002) Preoperative paclitaxel and concurrent rapid-fractionation radiation for respectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol 20:2537–2544PubMedCrossRefGoogle Scholar
  50. Pisters PW, Wolff RA et al. (2005) Combined-modality treatment for operable pancreatic adenocarcinoma. Oncology 19:393–404PubMedGoogle Scholar
  51. Rich TA, Janjan NA et al. (1997) Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 15:3292–3293Google Scholar
  52. Rich T, Harris J et al. (2004) Phase II study of external irradiation and weekly paclitaxel for nonmetastatic, unresectable pancreatic cancer: RTOG-98-12. Am J Clin Oncol 27:51–56PubMedCrossRefGoogle Scholar
  53. Safran H, Akerman P et al. (1999) Paclitaxel and concurrent radiation therapy for locally advanced adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. Semin Radiat Oncol 9[2 Suppl 1]:53–57PubMedGoogle Scholar
  54. Saif MW, Eloubeidi MA et al. (2005a) Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome. J Clin Oncol 23:8679–8687PubMedCrossRefGoogle Scholar
  55. Saif M, Moody J et al. (2005b) Gastrointestinal bleeding associated with concurrent capecitabine and radiotherapy in patients with pancreatic cancer. J Pancreas 6:325–333Google Scholar
  56. Sohn TA, Yeo CJ et al. (2000) Resected adenocarcinoma of the pancreas — 616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 4:567–579PubMedCrossRefGoogle Scholar
  57. Tamm EP, Silverman PM et al. (2003) Diagnosis, staging, and surveillance of pancreatic cancer. Am J Roentgenol 180:1311–1323Google Scholar
  58. Todd KE, Gloor B et al. (1998) Resection of locally advanced pancreatic cancer after downstaging with continuous-infusion 5-fluorouracil, mitomycin-C, leucovorin, and dipyridamole. J Gastrointest Surg 2:159–166PubMedCrossRefGoogle Scholar
  59. Wey J, Fan F et al. (2005) Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines. Cancer 104:427–438PubMedCrossRefGoogle Scholar
  60. White R, Lee C et al. (1999) Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol 6:38–45PubMedCrossRefGoogle Scholar
  61. Whittington R, Neuberg D et al. (1995) Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group trial. J Clin Oncol 13:227–232PubMedGoogle Scholar
  62. Wilkowski R, Heinemann V et al. (2000) Radiochemotherapy including gemcitabine and 5-fluorouracil for treatment of locally advanced pancreatic cancer. Proc Am Soc Clin Oncol 19:1078 (abstract)Google Scholar
  63. Willett CG, Safran H et al. (2003) Clinical research in pancreatic cancer: the Radiation Therapy Oncology Group trials. Int J Radiat Oncol Biol Phys 56:31–37PubMedCrossRefGoogle Scholar
  64. Willett CG, Boucher Y et al. (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nature Med 10:145–147PubMedCrossRefGoogle Scholar
  65. Willett CG, Boucher Y et al. (2005) Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 23:8136–8139PubMedCrossRefGoogle Scholar
  66. Wolff RA, Evans DB et al. (2001) Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Res 7:2246–2253PubMedGoogle Scholar
  67. Wolff RA, Evans DB et al. (2002) Initial results of a preoperative gemcitabine (GEM)-based chemoradiation for respectable pancreatic adenocarcinoma (Abstract). Proc Am Soc Clin Oncol 21:130aGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Christopher H. Crane
    • 1
  • Gauri Varadhachary
    • 2
  • Peter W. T. Pisters
    • 3
  • Douglas B. Evans
    • 3
  • Robert A. Wolff
    • 2
  1. 1.Department of Radiation OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Gastrointestinal Medical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of Surgical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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