Advertisement

Novel Approaches in Chemoradiation for Localized Pancreas Cancer

  • Christopher H. Crane
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)

Attempts to improve results of chemoradiotherapy in patients with pancreatic cancer by either increasing the total dose of radiation or chemotherapy or by changing cytotoxic drugs have not been very successful. Additionally, some combinations have been associated with a high rate of unacceptable treatment-related morbidity, underscoring the need for new treatment strategies to combine with radiation to improve the therapeutic ratio of such treatment. Gemcitabine has stood the test of time as a systemic agent in advanced and early disease but was not widely adopted as a radiosensitizer in pancreatic cancer. Single-arm clinical trials that initially explored gemcitabine as a radiosensitizer in locally advanced pancreatic cancer demonstrated the potential for significant toxicity without dramatic improvements in efficacy. Subsequent studies showed marked improvement in patient tolerance with the refinements of delivery of radiation. Recent strategies include radiosensitization by the incorporation of targeted agents and continued improvement in delivery of radiation through novel means such as steriotactic radiotherapy. This chapter focuses on data evaluating the incorporation of targeted agents with radiation therapy in the context of a multidisciplinary approach for the treatment of localized pancreatic cancer.

Keywords

Epidermal Growth Factor Receptor Pancreatic Cancer Rectal Cancer Clin Oncol Radiat Oncol Biol Phys 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kim IA, Bae SS, Fernandes A, 2005, Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines. Cancer Res 65 (17):7902–7910.PubMedGoogle Scholar
  2. 2.
    McKenna WG, Muschel RJ, 2003, Targeting tumor cells by enhancing radiation sensitivity. Genes Chromosomes Cancer 38(4):330–338.CrossRefPubMedGoogle Scholar
  3. 3.
    Hurwitz H, Fehrenbacher L, Novotny W, 2004, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342[see comment].CrossRefPubMedGoogle Scholar
  4. 4.
    Kabbinavar FF, Hambleton J, Mass RD, 2005, Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23:3706–3712.CrossRefPubMedGoogle Scholar
  5. 5.
    Gorski DH, Beckett MA, Jaskowiak NT, 1999, Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 59:3374–3378.PubMedGoogle Scholar
  6. 6.
    Wey J, Fan F, Gray M, 2005, Vascular endothelial growth factor receptor-1 promotes migra-tion and invasion in pancreatic carcinoma cell lines. Cancer 104:427–438.CrossRefPubMedGoogle Scholar
  7. 7.
    Jain RK. 2005, Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Willett CG, Boucher Y, di Tomaso E, 2004, Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147[see com-ment] [erratum appears in Nat Med 2004, 10(6):649].CrossRefPubMedGoogle Scholar
  9. 9.
    Willett CG, Boucher Y, Duda DG, 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 23:8136–8139.CrossRefPubMedGoogle Scholar
  10. 10.
    Bonnen M, Crane C, Vauthey J-N, 2004, Long-term results using local excision after preoper-ative chemoradiation among selected T3 rectal cancer patients. Int J Radiat Oncol Biol Phys 60:1098–1105.CrossRefPubMedGoogle Scholar
  11. 11.
    Crane CH, Ellis LM, Abbruzzese JL, 2006, Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. J Clin Oncol 24:1145–1151.CrossRefPubMedGoogle Scholar
  12. 12.
    Milas L, Fan Z, Andratschke NH, 2004, Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies. Int J Radiat Oncol Biol Phys 58 (3): 966–971.PubMedGoogle Scholar
  13. 13.
    Solomon B, Hagekyriakou J, Trivett MK, 2003, EGFR blockade with ZD1839 (“Iressa”) potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cell carcinoma. Epidermal growth factor receptor. Int J Radiat Oncol Biol Phys. 55 (3): 713–723.PubMedGoogle Scholar
  14. 14.
    Chinnaiyan P, Huang S, Vallabhaneni G, 2005, Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res 65:3328–3335.PubMedGoogle Scholar
  15. 15.
    Fukutome M, Maebayashi K, Nasu S, 2006, Enhancement of radiosensitivity by dual inhibi-tion of the HER family with ZD1839 (“Iressa”) and trastuzumab (“Herceptin”). Int J Radiat Oncol Biol Phys 66 (2): 528–536.PubMedGoogle Scholar
  16. 16.
    Bonner JA, Harari PM, Giralt J, 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578.CrossRefPubMedGoogle Scholar
  17. 17.
    Machiels J, Sempoux C, Scalliet P, et al. Phase I study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. J Clin Oncol 2006, 24(18S) Abstract 3552.Google Scholar
  18. 18.
    Chung K, Minsky B, Schrag D, et al. Phase I trial of preoperative cetuximab with concurrent continuous infusion 5-fluorouracil and pelvic radiation in patients with local-regionally advanced rectal cancer. J Clin Oncol 2006, 24(18S):Abstract 3560.Google Scholar
  19. 19.
    Iannitti DMD, Dipetrillo TMD, Akerman PMD, 2005, Erlotinib and chemoradiation followed by maintenance erlotinib for locally advanced pancreatic cancer: a phase I study. Am J Clin Oncol 28:570–575.CrossRefPubMedGoogle Scholar
  20. 20.
    Czito BG, Willett CG, Bendell JC, 2006, Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results. J Clin Oncol 24:656–662.CrossRefPubMedGoogle Scholar
  21. 21.
    Milas L, Mason KA, Crane CH, 2003, Improvement of radiotherapy or chemoradiotherapy by targeting COX-2 enzyme. Oncology 17(5 Suppl 5):15–24.PubMedGoogle Scholar
  22. 22.
    Choi H, Milas L. 2003, Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance? J Natl Cancer Inst 95(19):1440–1452.Google Scholar
  23. 23.
    Crane CH, Antolak JA, Rosen II, 2001, Phase I study of concomitant gemcitabine and IMRT for patients with unresectable adenocarcinoma of the pancreatic head. Int J Gastrointest Cancer 30:123–132.CrossRefPubMedGoogle Scholar
  24. 24.
    Koong AC, Christofferson E, Le Q-T, 2005, Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 63: 320–323.PubMedGoogle Scholar
  25. 25.
    Koong AC, Le QT, Ho A, 2004, Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 58: 1017–1021.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Christopher H. Crane
    • 1
  1. 1.M. D. Anderson Cancer Center, Radiation Oncology DepartmentThe University of TexasHoustonUSA

Personalised recommendations