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Chemoradiotherapy for unresectable pancreatic cancer

  • From the Asco-Jsco Joint Symposium
  • Published:
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Abstract

Treatment options for unresectable pancreatic cancer, including concurrent chemoradiotherapy, chemotherapy alone, and chemotherapy followed by chemoradiotherapy, are largely ineffective and result in a median survival of approximately 10–12 months. Although quality data on the benefit of radiotherapy in unresectable pancreatic cancer are lacking, it seems unlikely that the low-efficacy chemotherapy used for pancreatic cancer would control gross disease. Current regimens deliver low, ineffective doses of radiation and are associated with high rates of local failure. New technological advances, such as intensity-modulated radiotherapy, now allow the safe delivery of high-dose, highly conformal radiotherapy concurrently with full systemic doses of chemotherapy. We review new knowledge related to pattern of failure, target definition, and target motion and discuss the implications of these data on modern radiotherapy treatment planning and delivery. While it is clear that breakthroughs in treatment would come mostly from advances in systemic therapy, the evidence suggests that radiotherapy should not fall out of use, but rather be intensified.

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References

  1. Moertel CG, Frytak S, Hahn RG, 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 48:1705–1710

    Article  PubMed  CAS  Google Scholar 

  2. Gastrointestinal Tumor Study Group (1988) Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 80:751–755

    Article  Google Scholar 

  3. Klaassen DJ, MacIntyre JM, Catton GE, 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 3:373–378

    PubMed  CAS  Google Scholar 

  4. Berlin JD, Catalano P, Thomas JP, et al. (2002) 3rd. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20:3270–3275

    Article  PubMed  CAS  Google Scholar 

  5. Bramhall SR, Schulz J, Nemunaitis J, et al. (2002) A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer 87:161–167

    Article  PubMed  CAS  Google Scholar 

  6. Van Cutsem E, van de Velde H, Karasek P, et al. (2004) Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 22:1430–1438

    Article  PubMed  Google Scholar 

  7. Rocha Lima CM, Green MR, Rotche R, et al. (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22:3776–3783

    Article  PubMed  CAS  Google Scholar 

  8. Isacoff WH, Bendetti JK, Barstis JJ, et al. (2007) Phase II trial of infusional fluorouracil, leucovorin, mitomycin, and dipyridamole in locally advanced unresectable pancreatic adenocarcinoma: SWOG S9700. J Clin Oncol 25:1665–1669

    Article  PubMed  CAS  Google Scholar 

  9. Burris HA, 3rd, Moore MJ, Andersen J, 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 15:2403–2413

    PubMed  CAS  Google Scholar 

  10. Lawrence TS, Chang EY, Hahn TM, et al. (1996) Radiosensitization of pancreatic cancer cells by 2′, 2′-difluoro-2′-deoxycytidine. Int J Radiat Oncol Biol Phys 34:867–872

    PubMed  CAS  Google Scholar 

  11. Lawrence TS, Eisbruch A, Shewach DS. (1997) Gemcitabine-mediated radiosensitization. Semin Oncol 24(2 Suppl 7):S7-24–S27-28

    Google Scholar 

  12. Shewach DS, Hahn TM, Chang E, et al. (1994) Metabolism of 2′,2′-difluoro-2′-deoxycytidine and radiation sensitization of human colon carcinoma cells. Cancer Res 54:3218–3223

    PubMed  CAS  Google Scholar 

  13. McGinn CJ, Zalupski MM, Shureiqi I, 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 19:4202–4208

    PubMed  CAS  Google Scholar 

  14. McGinn CJ, Talamonti MS, Small W, et al. (2004) A phase II trial of full-dose gemcitabine with concurrent radiation therapy in patients with resectable or unresectable non-metastatic pancreatic cancer. Program/Proceedings Gastrointestinal Cancers Symposium, San Francisco, 22–24 Jan 2004 (abstract 96)

  15. Talamonti MS, Small W, Jr., Mulcahy MF, et al. (2006) A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol 13:150–158

    Article  PubMed  Google Scholar 

  16. Murphy JD, Adusumilli S, Griffith KA, et al. (2007) Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 68:801–808

    PubMed  CAS  Google Scholar 

  17. Crane CH, Janjan NA, Evans DB, et al. (2001) Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer. Int J Pancreatol 29:9–18

    PubMed  CAS  Google Scholar 

  18. Okusaka T, Ito Y, Ueno H, et al. (2004) Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. Br J Cancer 91:673–677

    PubMed  CAS  Google Scholar 

  19. Blackstock AW, Tepper JE, Niedwiecki D, et al. (2003) Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas. Int J Gastrointest Cancer 34:107–116

    Article  PubMed  CAS  Google Scholar 

  20. Li CP, Chao Y, Chi KH, 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 57:98–104

    PubMed  CAS  Google Scholar 

  21. Huguet F, Andre T, Hammel P, et al. (2007) Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 25:326–331

    Article  PubMed  CAS  Google Scholar 

  22. Krishnan S, Rana V, Janjan NA, et al. (2007) Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer 110:47–55

    Article  PubMed  Google Scholar 

  23. Haslam JB, Cavanaugh PJ, Stroup SL (1973) Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer 32:1341–1345

    Article  PubMed  CAS  Google Scholar 

  24. de Lange SM, van Groeningen CJ, Meijer OW, et al. (2002) Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer. Eur J Cancer 38:1212–1217

    Article  PubMed  Google Scholar 

  25. Magnino A, Gatti M, Massucco P, et al. (2005) Phase II trial of primary radiation therapy and concurrent chemotherapy for patients with locally advanced pancreatic cancer. Oncology 68: 493–499

    Article  PubMed  CAS  Google Scholar 

  26. Ko AH, Quivey JM, Venook AP, et al. (2007) A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 68:809–816

    PubMed  CAS  Google Scholar 

  27. Bussels B, Goethals L, Feron M, et al. (2003) Respiration-induced movement of the upper abdominal organs: a pitfall for the three-dimensional conformal radiation treatment of pancreatic cancer. Radiother Oncol 68:69–74

    Article  PubMed  Google Scholar 

  28. Feng M, Balter JM, Normolle D, et al. (2007) Characterization of Pancreatic Tumor Motion Using 4D MRI: Surrogates for Tumor Position Should be Used With Caution. Int J Radiat Oncol Biol Phys 69:S3

    Google Scholar 

  29. Ceha HM, van Tienhoven G, Gouma DJ, et al. (2000) Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma. Cancer 89:2222–2229

    Article  PubMed  CAS  Google Scholar 

  30. Spalding AC, Jee KW, Vineberg K, et al. (2007) Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions. Med Phys 34:521–529

    Article  PubMed  Google Scholar 

  31. Ishii H, Okada S, Tokuuye K, et al. (1997) Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. Cancer 79:1516–1520

    Article  PubMed  CAS  Google Scholar 

  32. Mawdsley S, Hall M, Glynne-Jones R. (2002) Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil. Clin Oncol (R Coll Radiol) 14:308–312

    CAS  Google Scholar 

  33. Osti MF, Costa AM, Bianciardi F, et al. (2001) Concomitant radiotherapy with protracted 5-fluorouracil infusion in locally advanced carcinoma of the pancreas: a phase II study. Tumori 87:398–401

    PubMed  CAS  Google Scholar 

  34. Boz G, De Paoli A, Innocente R, et al. (2001) Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma. Int J Radiat Oncol Biol Phys 51:736–740

    PubMed  CAS  Google Scholar 

  35. Crane CH, Winter K, Regine W, et al. (2007) A phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 69:S77

    Google Scholar 

  36. Bramhall SR, Rosemurgy A, Brown PD, et al. (2001) Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 19:3447–3455

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Michigan Medical Center, UH-B2C490 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0010, USA

    Edgar Ben-Josef & Theodore S. Lawrence

Authors
  1. Edgar Ben-Josef
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  2. Theodore S. Lawrence
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Correspondence to Edgar Ben-Josef.

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Ben-Josef, E., Lawrence, T.S. Chemoradiotherapy for unresectable pancreatic cancer. Int J Clin Oncol 13, 121–126 (2008). https://doi.org/10.1007/s10147-007-0763-x

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  • DOI: https://doi.org/10.1007/s10147-007-0763-x

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