Seminars in Oncology
Volume 34, Issue 4 , Pages 335-346 , August 2007

Future Chemoradiation Strategies in Pancreatic Cancer

  • Christopher H. Crane

      Affiliations

    • Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
    • Corresponding Author InformationAddress correspondence to Christopher H. Crane, MD, Department of Radiation Oncology, Unit 97, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
  • ,
  • Gauri Varadhachary

      Affiliations

    • Department of Gastrointestinal Oncology and Digestive Diseases, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
  • ,
  • Peter W.T. Pisters

      Affiliations

    • Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
  • ,
  • Douglas B. Evans

      Affiliations

    • Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
  • ,
  • Robert A. Wolff

      Affiliations

    • Department of Gastrointestinal Oncology and Digestive Diseases, The University of Texas M.D. Anderson Cancer Center, Houston, TX.

References 

  1. In:  Greene FL,  Page DL,  Fleming ID, et al. editor. AJCC Cancer Staging Manual. (ed 6). New York, NY: Springer; 2002;p. 157–164
  2. Tseng JF, Raut CP, Lee JE, Pisters PW, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg. 2004;8:935–949
  3. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–730
  4. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991;324:709–715
  5. Gastrointestinal Tumor Study Group. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer. 1987;59:2006–2010
  6. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–646
  7. Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: Treatment variables and survival duration. Ann Surg Oncol. 2001;8:123–132
  8. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: Results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–579
  9. Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: A population-based, linked database analysis of 396 patients. Ann Surg. 2003;237:74–85
  10. Klinkenbijl JH, Jeekel J, Sahmoud T, et al. 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. 1999;230:776–782
  11. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–1210
  12. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–1740
  13. Raut CP, Evans DB, Crane CH, et al. Neoadjuvant therapy for resectable pancreatic cancer. Surg Oncol Clin North Am. 2004;4:639–661
  14. Pisters PWT, Wolff RA, Janjan NA, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: Toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002;20:2537–2544
  15. Pisters PW, Abbruzzese JL, Janjan NA, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16:3843–3850
  16. Lowy AM, Lee JE, Pisters PW, et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Ann Surg. 1997;226:632–641
  17. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas—616 patients: Results, outcomes, and prognostic indicators. J Gastrointestinal Surg. 2000;4:567–579
  18. Pisters PW, Wolff RA, Crane CH, et al. Combined-modality treatment for operable pancreatic adenocarcinoma. Oncology. 2005;19:393–404
  19. Pisters PWT, Abbruzzese JL, Janjan NA, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16:3843–3850
  20. Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–1339
  21. Wolff RA, Evans DB, Crane CH, et al. Initial results of a preoperative gemcitabine (GEM)-based chemoradiation for resectable pancreatic adenocarcinoma. Proc Am Soc Clin Oncol. 2002;21:130a;(abstr)
  22. Wolff RA, Evans DB, Gravel DM, et al. Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. Clin Cancer Res. 2001;7:2246–2253
  23. Rich TA, Janjan NA, Abbruzzese JL, et al. (Response) Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:3292–3293
  24. Pisters PWT, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann Surg. 2001;234:47–55
  25. Pisters PWT, Hudec WA, Lee JE, et al. Preoperative chemoradiation for patients with pancreatic cancer: Toxicity of endobiliary stents. J Clin Oncol. 2000;18:860–867
  26. Suits J, Frazee R, Erickson RA. Endoscopic ultrasound and fine needle aspiration for the evaluation of pancreatic masses. Arch Surg. 1999;134:639–643
  27. Faigel D, Ginsberg G, Bentz J, et al. Endoscopic ultrasound-guided real-time fine-needle aspiration biopsy of the pancreas in cancer patients with pancreatic lesions. J Clin Oncol. 1997;15:1439–1443
  28. Hoffman JP, Lipsitz S, Pisansky T, et al. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: An Eastern Cooperative Oncology Group study. J Clin Oncol. 1998;16:317–323
  29. Povoski SP, Karpeh MS, Conlon KC, et al. Association of preoperative biliary drainage with postoperative outcome following pancreaticoduodenectomy. Ann Surg. 1999;230:131–142
  30. The Gastrointestinal Tumor Study Group. A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. Ann Surg. 1979;189:205–208
  31. Moertel CG, Frytak S, Hahn RG, et al. 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. 1981;48:1705–1710
  32. Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst. 1988;80:751–755
  33. Gastrointestinal Tumor Study Group. Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Cancer. 1985;56:2563–2568
  34. Klaassen DJ, MacIntyre JM, Catton GE, et al. 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. 1985;3:373–378
  35. Whittington R, Neuberg D, Tester WJ, et al. 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. 1995;13:227–232
  36. Ishii H, Okada S, Tokuuye K, et al. Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. Cancer. 1997;79:1516–1520
  37. Pipas JM, Mitchell SE, Barth RJ, et al. Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys. 2001;50:1317–1322
  38. McGinn CJ, Zalupski MM, Shureiqi I, et al. Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2001;19:4202–4208
  39. Blackstock AW, Bernard SA, Richards F, et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol. 1999;17:2208–2212
  40. Crane CH, Wolff RA, Abbruzzese JL, et al. Combining gemcitabine with radiation in pancreatic cancer: Understanding important variables influencing the therapeutic index. Semin Oncol. 2001;28:25–33
  41. Li C-P, Chao Y, Chi K-H, et al. Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: Gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Physics. 2003;57:98–104
  42. Blackstock A, Tempero M, Niedwiecki D, et al. Cancer and Leukemia Group B (CALGB) 89805: Phase II chemoradiation trial using gemcitabine in patients with localoregional adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Physics. 2001;51:31;(abstr 49)
  43. McGinn CJ, Zalupski MM, Shureiqi I, et al. Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2001;19:4202–4208
  44. McGinn C, Talamonti M, Small W, et al: A phase II trial of full-dose gemcitabine with concurrent radiation therapy in patients with resectable or unresectable non-metastatic pancreatic cancer. Proceedings of the 2004 ASCO Gastrointestinal Symposium, San Francisco, CA, January 16-18, 2004, p 89 (abstr 96)
  45. Burris HA, Moore MJ, Andersen J, 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;15:2403–2413
  46. Crane CH, Abbruzzese JL, Evans DB, et al. 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 Physics. 2002;52:1293–1302
  47. Twelves C, Weng A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352:2696–2704
  48. Cartwright TH, Cohn A, Varkey JA, et al. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol. 2002;20:160–164
  49. Dunst J, Reese T, Sutter T, et al. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol. 2002;20:3983–3991
  50. Crane C, Ellis L, Abbruzzese J, et al. Phase I trial of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic adenocarcinoma. J Clin Oncol. 2006;24:1145–1151
  51. Ben-Josef E, Shields AF, Vaishampayan U, et al. Intensity-modulated radiotherapy (IMRT) and concurrent capecitabine for pancreatic cancer. Int J Radiat Oncol Biol Physics. 2004;59:454–459
  52. Saif MW, Eloubeidi MA, Russo S, et al. 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. 2005;23:8679–8687
  53. Gorski DH, Beckett MA, Jaskowiak NT, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59:3374–3378
  54. Wey J, Fan F, Gray M, et al. Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines. Cancer. 2005;104:427–438
  55. Jain RK. Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science. 2005;307:58–62
  56. Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–147
  57. Iannitti DMD, Dipetrillo TMD, Akerman PMD, et al. Erlotinib and chemoradiation followed by maintenance erlotinib for locally advanced pancreatic cancer: A phase I study. Am J Clin Oncol. 2005;28:570–575
  58. Czito BG, Willett CG, Bendell JC, et al. Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: Phase I trial results. J Clin Oncol. 2006;24:656–662
  59. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–578
  60. Tamm EP, Silverman PM, Charnsangavej C, et al. Diagnosis, staging, and surveillance of pancreatic cancer. AJR. 2003;180:1311–1323
  61. Cusack JC, Fuhrman GM, Lee JE, et al. Management of unsuspected tumor invasion of the superior mesenteric-portal venous confluence at the time of pancreaticoduodenectomy. Am J Surg. 1994;168:352–354
  62. Jessup JM, Steele G, Mayer RJ, et al. Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg. 1993;128:559–564
  63. Jeekel J, Treurniet-Donker AD. Treatment perspectives in locally advanced unresectable pancreatic cancer. Br J Surg. 1991;78:1332–1334
  64. White R, Lee C, Anscher M, et al. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol. 1999;6:38–45
  65. Todd KE, Gloor B, Lane JS, et al. Resection of locally advanced pancreatic cancer after downstaging with continuous-infusion 5-fluorouracil, mitomycin-C, leucovorin, and dipyridamole. J Gastrointest Surg. 1998;2:159–166
  66. Bajetta E, Di Bartolomeo M, Stani SC, et al. Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: Results of a feasibility study. Int J Radiat Oncol Biol Physics. 1999;45:285–289
  67. Kornek GV, Schratter-Sehn A, Marczell A, et al. Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin. Br J Cancer. 2000;82:98–103
  68. Mehta VK, Fisher G, Ford JA, et al. Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg. 2001;5:27–35
  69. Koong AC, Le QT, Ho A, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Physics. 2004;58:1017–1021

 Supported in part by Grants No. CA06294 and CA16672 from the National Cancer Institute, Department of Health and Human Services, C.H.C. has received research support by Genentech and Bristol Meyers Squibb and honoraria from Roche.

PII: S0093-7754(07)00096-6

doi: 10.1053/j.seminoncol.2007.05.001

Seminars in Oncology
Volume 34, Issue 4 , Pages 335-346 , August 2007