Skip to main content
SpringerLink
Log in

Cytoprotection for Radiation-Associated Normal Tissue Injury

  • Chapter
Radiation Oncology Advances

Part of the book series: Cancer Treatment and Research ((CTAR,volume 139))

One of the cornerstones of radiation therapy is the delivery of therapeutic radiation doses to the target tissue, yet minimization of dose to surrounding normal tissue. In practice, there is always some dose delivered to surrounding normal tissue. Pure restriction of dose to the target volume, without any incidental irradiation of normal tissue, is physically impossible for most situations. Furthermore, the normal tissue effects of radiation are typically increased when concurrent chemotherapy and radiotherapy (RT) are used [1]. Concurrent chemoradiotherapy has been demonstrated to be superior, with regard to local control and/or survival, compared to single modality alone [2], in multiple disease sites such as the head and neck [3–6], lung [7–10], and pelvis [11–15]. Therefore, it is incumbent upon physicians to do what is possible to minimize the risks associated with incidental irradiation of normal tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Wasserman TH, Brizel DM, Henke M, et al. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial. Int J Radiat Oncol Biol Phys 2005; 63(4):985–990.

    CAS  PubMed  Google Scholar 

  2. Brizel DM. Strategies for Protecting Normal Tissue in the Treatment of Head and Neck Cancer. Totowa, NJ: Humana Press, Inc.; 2005.

    Google Scholar 

  3. Wendt TG, Grabenbauer GG, Rodel CM, et al. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 1998; 16(4):1318–1324.

    CAS  PubMed  Google Scholar 

  4. Dobrowsky W, Naude J. Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancers. Radiother Oncol 2000; 57(2):119–124.

    CAS  PubMed  Google Scholar 

  5. Denis F, Garaud P, Bardet E, et al. Final results of the 94–01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 2004; 22(1): 69–76.

    Article  PubMed  Google Scholar 

  6. Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 1990; 323(14):940–945.

    Article  CAS  PubMed  Google Scholar 

  7. Rowell NP, O’Rourke N P. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev 2004(4):CD002140.

    Google Scholar 

  8. Byhardt RW, Scott C, Sause WT, et al. Response, toxicity, failure patterns, and survival in five Radiation Therapy Oncology Group (RTOG) trials of sequential and/or concurrent chemotherapy and radiotherapy for locally advanced non-small-cell carcinoma of the lung. Int J Radiat Oncol Biol Phys 1998; 42(3):469–478.

    Article  CAS  PubMed  Google Scholar 

  9. Lam CW, Chen WT, Liu MT, et al. Effect of preoperative concurrent chemoradiotherapy in locally advanced low rectal cancer after radical resection surgery. Int Surg 2005; 90(1):53–59.

    Article  PubMed  Google Scholar 

  10. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999; 340(15):1144–1153.

    Article  CAS  PubMed  Google Scholar 

  11. Kocak Z, Yu X, Zhou SM, et al. The impact of pre-radiotherapy surgery on radiation-induced lung injury. Clin Oncol (R Coll Radiol) 2005; 17(4):210–216.

    CAS  PubMed  Google Scholar 

  12. Capizzi RL. The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine. Semin Oncol 1999; 26(2 Suppl 7):3–21.

    Article  CAS  Google Scholar 

  13. Holwitt EA, Koda E, Swenberg CE. Enhancement of topoisomerase I-mediated unwinding of supercoiled DNA by the radioprotector WR-33278. Radiat Res 1990; 124(1):107–109.

    Article  PubMed  Google Scholar 

  14. Peters GJ, van der Vijgh WJ. Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (WR-2721): preclinical aspects. Eur J Cancer 1995; 31A(Suppl 1):S1–S7.

    Google Scholar 

  15. Culy CR, Spencer CM. Amifostine: an update on its clinical status as a cytoprotectant in patients with cancer receiving chemotherapy or radiotherapy and its potential therapeutic application in myelodysplastic syndrome. Drugs 2001; 61(5):641–684.

    Article  CAS  PubMed  Google Scholar 

  16. Travis EL. The oxygen dependence of protection by aminothiols: implications for normal tissues and solid tumors. Int J Radiat Oncol Biol Phys 1984; 10(9):1495–1501.

    CAS  PubMed  Google Scholar 

  17. Wasserman TH. Radiotherapeutic studies with amifostine (Ethyol). Semin Oncol 1994; 21(5 Suppl 11):21–25.

    Article  CAS  PubMed  Google Scholar 

  18. Tresher M NL, Shepman A, et al. Effects of modulating agent WR-2721 and its main metabolites on the formaiton and stability of cisplatin/DNA adducts in vitro. Bio Chem Pharmacol 1992; 33:1013.

    Google Scholar 

  19. Grdina DJ, Murley JS, Kataoka Y. Radioprotectants: current status and new directions. Oncology 2002; 63(Suppl 2):2–10.

    Article  CAS  PubMed  Google Scholar 

  20. Gornitsky M, Shenouda G, Sultanem K, et al. Double-blind randomized, placebo-controlled study of pilocarpine to salvage salivary gland function during radiotherapy of patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98(1):45–52.

    CAS  PubMed  Google Scholar 

  21. Wiseman LR, Faulds D. Oral pilocarpine: a review of its pharmacological properties and clinical potential in xerostomia. Drugs 1995; 49(1):143–155.

    Article  CAS  PubMed  Google Scholar 

  22. Rode M, Smid L, Budihna M, Soba E, Rode M, Gaspersic D. The effect of pilocarpine and biperiden on salivary secretion during and after radiotherapy in head and neck cancer patients. Int J Radiat Oncol Biol Phys 1999; 45(2):373–378.

    Google Scholar 

  23. Baumann M, Krause M, Zips D, et al. Molecular targeting in radiotherapy of lung cancer. Lung Cancer 2004; 45 Suppl 2:S187–S197.

    Google Scholar 

  24. Housley RM, Morris CF, Boyle W, et al. Keratinocyte growth factor induces proliferation of hepatocytes and epithelial cells throughout the rat gastrointestinal tract. J Clin Invest 1994; 94(5):1764–1777.

    Article  CAS  PubMed  Google Scholar 

  25. Yi ES, Shabaik AS, Lacey DL, et al. Keratinocyte growth factor causes proliferation of urothelium in vivo. J Urol 1995; 154(4):1566–1570.

    Article  CAS  PubMed  Google Scholar 

  26. Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA. Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 1989; 86(3):802–806.

    CAS  PubMed  Google Scholar 

  27. Danilenko DM. Preclinical and early clinical development of keratinocyte growth factor, an epithelial-specific tissue growth factor. Toxicol Pathol 1999; 27(1):64–71.

    Article  CAS  PubMed  Google Scholar 

  28. Buentzel J, Micke O, Adamietz IA, Monnier A, Glatzel M, de Vries A. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase III study. Int J Radiat Oncol Biol Phys 2005.

    Google Scholar 

  29. Vacha P, Fehlauer F, Mahlmann B, et al. Randomized phase III trial of postoperative radiochemotherapy +/− amifostine in head and neck cancer. Is there evidence for radioprotection? Strahlenther Onkol 2003; 179(6):385–389.

    Google Scholar 

  30. Bourhis J, De Crevoisier R, Abdulkarim B, et al. A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2000; 46(5):1105–1108.

    Article  CAS  PubMed  Google Scholar 

  31. Koukourakis MI, Kyrias G, Kakolyris S, et al. Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study. J Clin Oncol 2000; 18(11):2226–2233.

    CAS  PubMed  Google Scholar 

  32. Antonadou D, Coliarakis N, Synodinou M, et al. Randomized phase III trial of radiation treatment + /− amifostine in patients with advanced-stage lung cancer. Int J Radiat Oncol Biol Phys 2001; 51(4):915–922.

    Article  CAS  PubMed  Google Scholar 

  33. Movsas B, Scott C, Langer C, et al. Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98–01. J Clin Oncol 2005; 23(10): 2145–2154.

    Article  CAS  PubMed  Google Scholar 

  34. Antonadou D, Throuvalas N, Petridis A, Bolanos N, Sagriotis A, Synodinou M. Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003; 57(2):402–408.

    Article  CAS  PubMed  Google Scholar 

  35. Senzer N. A phase III randomized evaluation of amifostine in stage IIIA/IIIB non-small cell lung cancer patients receiving concurrent carboplatin, paclitaxel, and radiation therapy followed by gemcitabine and cisplatin intensification: preliminary findings. Semin Oncol 2002; 29(6 Suppl 19):38–41.

    Article  CAS  PubMed  Google Scholar 

  36. Gopal R SG, Tucher S, Liao Z, Kelly J, Stevens C, Komaki R. The effects of radaition therapy, chemotherapy and the radioprotector amifostine o the diffusion capacity of patients with non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 2001; 51(3 Suppl 1):22.

    Google Scholar 

  37. Kligerman MM, Liu T, Liu Y, Scheffler B, He S, Zhang Z. Interim analysis of a randomized trial of radiation therapy of rectal cancer with/without WR-2721. Int J Radiat Oncol Biol Phys 1992; 22(4):799–802.

    Article  CAS  PubMed  Google Scholar 

  38. Bardet E, Martin L, Calais G, et al. Preliminary data of the GORTEC 2000–02 phase III trial comparing intravenous and subcutaneous administration of amifostine for head and neck tumors treated by external radiotherapy. Semin Oncol 2002; 29(6 Suppl 19):57–60.

    PubMed  Google Scholar 

  39. Kouloulias VE, Kouvaris JR, Pissakas G, et al. Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: topical intrarectal versus subcutaneous application. Int J Radiat Oncol Biol Phys 2005; 62(2):486–493.

    Article  CAS  PubMed  Google Scholar 

  40. Schraube P, Schell R, Wannenmacher M, Drings P, Flentje M. [Pneumonitis after radiotherapy of bronchial carcinoma: incidence and influencing factors]. Strahlenther Onkol 1997; 173(7):369–378.

    Article  PubMed  Google Scholar 

  41. Mehta V. Open label multicenter trial of subcutaneous amifostine (Ethyol) in the prevention of radiation induced esophagitis and pneumonitis in patients with measurable, unresectable non-small cell lung cancer. Semin Oncol 2004; 31(6 Suppl 18):42–46.

    Article  PubMed  CAS  Google Scholar 

  42. Skwarchuk MW, Jackson A, Zelefsky MJ, et al. Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose–response. Int J Radiat Oncol Biol Phys 2000; 47(1):103–113.

    Article  CAS  PubMed  Google Scholar 

  43. Montana GS, Anscher MS, Mansbach CM 2nd, et al. Topical application of WR-2721 to prevent radiation-induced proctosigmoiditis. A phase I/II trial. Cancer 1992; 69(11):2826–2830.

    Google Scholar 

  44. Mateos JJ, Setoain X, Ferre J, et al. Salivary scintigraphy for assessing the protective effect of pilocarpine in head and neck irradiated tumours. Nucl Med Commun 2001; 22(6):651–656.

    PubMed  Google Scholar 

  45. Kohler PF, Winter ME. A quantitative test for xerostomia. The Saxon test, an oral equivalent of the Schirmer test. Arthritis Rheum 1985; 28(10):1128–1132.

    Google Scholar 

  46. Ozturk B, Egehan I, Atavci S, Kitapci M. Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial. Int J Radiat Oncol Biol Phys 2004; 58(1):213–219.

    Google Scholar 

  47. Booth C, Booth D, Williamson S, Demchyshyn LL, Potten CS. Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage. Cell Prolif 2004; 37(6):385–400.

    Article  PubMed  Google Scholar 

  48. Cassatt DR, Fazenbaker CA, Kifle G, Bachy CM. Preclinical studies on the radioprotective efficacy and pharmacokinetics of subcutaneously administered amifostine. Semin Oncol 2002; 29(6 Suppl 19):2–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA

    Jingfang Mao M.D, Oluwatoyosi A. Fatunase BA & Lawrence B. Marks M.D

Authors
  1. Jingfang Mao M.D
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oluwatoyosi A. Fatunase BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence B. Marks M.D
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, K4/310, 53792, Madison, WI, USA

    Søren M. Bentzen Ph.D., D.Sc , Paul M. Harari M.D , Wolfgang A. Tomé M.D., Ph.D  & Minesh P. Mehta M.D , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Mao, J., Fatunase, O.A., Marks, L.B. (2008). Cytoprotection for Radiation-Associated Normal Tissue Injury. In: Bentzen, S.M., Harari, P.M., Tomé, W.A., Mehta, M.P. (eds) Radiation Oncology Advances. Cancer Treatment and Research, vol 139. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-36744-6_14

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-36744-6_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-36743-9

  • Online ISBN: 978-0-387-36744-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation