Seminars in Radiation Oncology
Volume 13, Issue 1 , Pages 73-84 , January 2003

Pharmacological intervention to prevent or ameliorate chronic radiation injuries

References 

  1. Withers HR, Peters LJ, Kogelnik HD. The pathobiology of late effects of irradiation. In:  Meyn RE,  Withers HR editor. Radiation biology in cancer research. New York, NY: Raven Press; 1980;p. 439–448
  2. Rubin P, Casarett GW. Clinical Radiation Pathology. Philadelphia, PA: Saunders; 1968;
  3. Moulder JE, Robbins MEC, Cohen EP. Pharmacologic modification of radiation-induced late normal tissue injury. Cancer Treat Res. 1998;93:129–151
  4. Hopewell JW. Modifying radiation injury to normal tissues: new opportunities. Front Radiat Ther Oncol. 1999;32:9–20
  5. Trott KR. Experimental radiotherapy of late-responding tissues—Recent advances and future development. Front Radiat Ther Oncol. 2002;37:9–16
  6. Stone HB, McBride WH, Coleman CN. Modifying normal tissue damage postirradiation. Radiat Res. 2002;157:204–223
  7. Ricks RC, Berger ME, O'Hara FM. The Medical Basis for Radiation-Accident Preparedness: The Clinical Care of Victims. New York, NY: The Parthenon Publishing Group; 2002;
  8. Moulder JE. Issues and updates: Report on an interagency workshop on the radiobiology of nuclear terrorism. Radiat Res. 2002;158:118–124
  9. Patt HM, Tyree EB, Straube RL. Cysteine protection against x-irradiation. Science. 1949;110:213–214
  10. Wasserman TH. Radiotherapeutic studies with amifostine (Ethyol). Semin Oncol. 1994;21:21–25
  11. Andreassen N, Grau C, Lindegaard JC. Radioprotectors: current status and future perspectives. Semin Radiat Oncol. 2003;13:XX–XX
  12. Jarrett DG. Medical management of radiological casualties. Bethesda, MD: Armed Forces Radiobiology Research Institute; 1999;
  13. Michalowski AS. On radiation damage to normal tissues and its treatment I. Growth factors. Acta Oncol. 1990;29:1017–1023
  14. Michalowski AS. On radiation damage to normal tissues and its treatment II. Anti-inflammatory drugs. Acta Oncol. 1994;33:139–157
  15. Geraci JP, Sun MC, Mariano MS. Amelioration of radiation nephropathy in rats by postirradiation treatment with dexamethasone and/or captopril. Radiat Res. 1995;143:58–68
  16. Caldwell WL. The effect of prednisolone on fatal post-irradiation nephritis in rabbits. Radiology. 1971;98:431–433
  17. Verheij M, Stewart FA, Oussoren Y. Amelioration of radiation nephropathy by acetylsalicylic acid. Int J Radiat Biol. 1995;67:587–596
  18. van Kleef EM, Te Poele JAM, Oussoren YG. Influence of acetylsalicylic acid on development of radiation-induced nephropathy. Int J Radiat Biol. 2000;76:1565–1573
  19. Blomstrand C, Johansson B, Rosengren B. Dexamethasone effect on blood brain-barrier damage caused by acute hypertension in X-irradiated rabbits. Acta Neurol Scand. 1975;52:331–334
  20. Tada E, Matsumoto K, Kinoshita K. The protective effect of dexamethasone against radiation damage induced by interstitial irradiation in normal monkey brain. Neurosurgery. 1997;41:217–219
  21. Martins AN, Severance RE, Henry JM. Experimental delayed radiation necrosis of the brain. Part 1: Effect of early dexamethasone treatment. J Neurosurg. 1979;51:587–596
  22. Halpern J, Kishel SP, Park J. Radiation induced brain edema in primates, studied with sequential brain CAT scanning and histopathology. Protective effect of sodium meclofenamate. A preliminary report. Res Commun Chem Pathol Pharmacol. 1984;45:463–470
  23. Delattre JY, Rosenblum MK, Thaler HT. A model of radiation myelopathy in the rat. Pathology, regional capillary permeability changes and treatment with dexamethasone. Brain. 1988;111:1319–1336
  24. Geraci JP, Mariano MS, Jackson KL. Effect of adrenalectomy on the latency of radiation myelopathy in rats. Radiat Res. 1993;134:179–186
  25. Moss WT, Haddy FJ, Sweany SK. Some factors altering the sensitivity of acute radiation pneumonitis: Variation with cortisone, heparin, and antibiotics. Radiology. 1960;75:50–54
  26. Phillips TL, Wharam MD, Margolis LW. Modification of radiation injury to normal tissues by chemotherapeutic agents. Cancer. 1975;35:1678–1684
  27. Gross NJ, Narine KR, Wade R. Protective effect of corticosteroids on radiation pneumonitis in mice. Radiat Res. 1988;113:112–119
  28. Geraci JP, Mariano MS, Jackson KL. Effects of dexamethasone on late radiation injury following partial-body and local organ exposures. Radiat Res. 1992;129:61–70
  29. Ward HE, Kemsley L, Davies L. The effect of steroids on radiation-induced lung disease in the rat. Radiat Res. 1993;136:22–28
  30. Gross NJ, Holloway NO, Narine KR. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis. Radiat Res. 1991;127:317–324
  31. Olivotto IA, Kim-Sing C, Bajdik CD. Effect of acetylsalicylic acid on radiation and cosmetic results after conservative surgery for early breast cancer: A randomized trial. Radiother Oncol. 1996;41:1–6
  32. Leborgne JH, Leborgne F, Zubizarreta E. Corticosteroids and radiation mucositis in head and neck cancer. A double-blind placebo-controlled randomized trial. Radiother Oncol. 1998;47:145–148
  33. Cohen EP, Fish BL, Moulder JE. Treatment of radiation nephropathy with captopril. Radiat Res. 1992;132:346–350
  34. Moulder JE, Fish BL, Cohen EP. Treatment of radiation nephropathy with ACE inhibitors. Int J Radiat Oncol Biol Phys. 1993;27:93–99
  35. Moulder JE, Fish BL, Cohen EP. Radiation nephropathy is treatable with an angiotensin converting enzyme inhibitor or an angiotensin II type-1 (AT1) receptor antagonist. Radiother Oncol. 1998;46:307–315
  36. Cohen EP, Moulder JE, Fish BL. Prophylaxis of experimental bone marrow transplant nephropathy. J Lab Clin Med. 1994;124:371–380
  37. Moulder JE, Fish BL, Cohen EP. Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy. Bone Marrow Transplant. 1997;19:729–736
  38. Juncos LI, Carrasco Dueñas S, Cornejo JC. Long-term enalapril and hydrochlorothiazide in radiation nephritis. Nephron. 1993;64:249–255
  39. Moulder JE, Fish BL, Cohen EP. Angiotensin II receptor antagonists in the prevention of radiation nephropathy. Radiat Res. 1996;146:106–110
  40. Moulder JE, Fish BL, Cohen EP. Angiotensin II receptor antagonists in the treatment and prevention of radiation nephropathy. Int J Radiat Biol. 1998;73:415–421
  41. Moser M. Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and calcium channel blocking agents: A review of potential benefits and possible adverse reactions. J Am Coll Cardiol. 1997;29:1414–1421
  42. Oikawa T, Freeman M, Lo W. Modulation of plasminogen activator inhibitor-1 in vivo: A new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int. 1997;51:164–172
  43. Moulder JE, Fish BL, Cohen EP. Dietary sodium modification and experimental radiation nephropathy. Int J Radiat Biol. 2002;78:903–911
  44. Cohen EP, Fish BL, Moulder JE. Angiotensin II infusion exacerbates radiation nephropathy. J Lab Clin Med. 1999;134:283–291
  45. Cohen EP, Fish BL, Moulder JE. The renin-angiotensin system in experimental radiation nephropathy. J Lab Clin Med. 2002;139:251–257
  46. Moulder JE, Fish BL, Regner KR. Angiotensin II blockade reduces radiation-induced proliferation in experimental radiation nephropathy. Radiat Res. 2002;157:393–401
  47. Ward WF, Kim YT, Molteni A. Radiation-induced pulmonary endothelial dysfunction in rats: Modification by an inhibitor of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys. 1988;15:135–140
  48. Ward WF, Molteni A, Ts'ao CH. Radiation pneumotoxicity in rats: Modification by inhibitors of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys. 1992;22:623–625
  49. Ward WF, Lin PP, Wong PS. Radiation pneumonitis in rats and its modification by the angiotensin-converting enzyme inhibitor captopril evaluated by high-resolution computed tomography. Radiat Res. 1993;135:81–87
  50. Molteni A, Moulder JE, Cohen EP. Control of radiation-induced pneumopathy and lung fibrosis by angiotensin converting enzyme inhibitors and an angiotensin II type 1 receptor blocker. Int J Radiat Biol. 2000;76:523–532
  51. Molteni A, Moulder JE, Cohen EP. Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker. Exp Biol Med. 2001;226:1016–1023
  52. Wang LW, Fu XL, Clough R. Can angiotensin-converting enzyme inhibitors protect against symptomatic radiation pneumonitis?. Radiat Res. 2000;153:405–410
  53. Moulder JE, Fish BL, Cohen EP: ACE inhibitors and AII receptor blockers in the treatment and prevention of bone marrow transplant nephropathy. Curr Pharm Design (in press)
  54. Antignac C, Gubler MC, Leverger G. Delayed renal failure with extensive mesangiolysis following bone marrow transplantation. Kidney Int. 1989;35:1336–1344
  55. Cohen EP, Lawton CA. Pathogenesis, prevention and management of radiation nephropathy. In:  Tobias JS,  Thomas PRM editor. Current radiation oncology. New York, NY: Oxford University Press Inc; 1998;p. 94–109
  56. Raife TJ, Lager DJ. Chronic thrombotic microangiopathy associated with antineoplastic therapy with minimal hematologic effects. Mayo Clin Proc. 2002;77:323–328
  57. Rosenberg ME, Smith LJ, Correa-Rotter R. The paradox of the renin-angiotensin system in chronic renal disease. Kidney Int. 1994;45:403–410
  58. Mackenzie HS, Ots M, Ziai F. Angiotensin receptor antagonists in experimental models of chronic renal failure. Kidney Int. 1997;52:S140–S143 (suppl)
  59. Maschio G, Marcantoni C. Angiotensin converting enzyme inhibitors in nondiabetic renal disease. Curr Opin Nephrol Hypertens. 1998;7:253–257
  60. Datta PK, Moulder JE, Fish BL. TGF-β1 production in radiation nephropathy: Role of angiotensin II. Int J Radiat Biol. 1999;75:473–479
  61. Attal M, Huguet F, Rubie H. Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: A prospective, randomized trial. Blood. 1993;82:732–736
  62. Marques LJ, Zheng L, Poulakis N. Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. Am J Respir Crit Care Med. 1999;159:508–511
  63. Dion MW, Hussey DH, Doornbos JF. Preliminary results of a pilot study of pentoxifylline in the treatment of late radiation soft tissue necrosis. Int J Radiat Oncol Biol Phys. 1990;19:401–407
  64. Price MJ, Li LT, Tward JD. Effect of nicotinamide and pentoxifylline on normal tissue and FSA tumor oxygenation. Acta Oncol. 1995;34:391–395
  65. Futran ND, Trotti A, Gwede C. Pentoxifylline in the treatment of radiation-related soft tissue injury: Preliminary observations. Laryngoscope. 1997;107:391–395
  66. Aygene E, Celikkanat S, Bilgili H. Pentoxifylline effects on acute and late complications after radiotherapy in rabbit. Otolaryngol Head Neck Surg. 2001;124:669–673
  67. Collingridge DR, Rockwell S. Pentoxifylline improves the oxygenation and radiation response of BA1112 rat rhabdomyosarcomas and EMT6 mouse mammary carcinomas. Int J Cancer. 2000;90:256–264
  68. Song CW, Hasegawa T, Kwon HC. Increase in tumor oxygenation and radiosensitivity caused by pentoxifylline. Radiat Res. 1992;130:205–210
  69. Lee I, Boucher Y, Demhartner TJ. Changes in tumor blood flow, oxygenation and interstitial pressure induced by pentoxifylline. Br J Cancer. 1994;69:492–496
  70. Sperduto PW, Song CW, Levitt SH. The in vitro radiosensitization of human glioblastoma with pentoxifylline. Am J Clin Oncol. 1993;16:407–411
  71. Kim SH, Khil MS, Ryu S. Enhancement of radiation response of human carcinoma cells in culture by pentoxifylline. Int J Radiat Oncol Biol Phys. 1993;25:61–65
  72. Ward WF, Kim YT, Molteni A. Pentoxifylline does not spare acute radiation reactions in rat lung and skin. Radiat Res. 1992;129:107–111
  73. Koh WJ, Stelzer KJ, Peterson LM. Effect of pentoxifylline on radiation-induced lung and skin toxicity in rats. Int J Radiat Oncol Biol Phys. 1995;31:71–77
  74. Dion MW, Hussey DH, Osborne JW. The effect of pentoxifylline on early and late radiation injury following fractionated irradiation in C3H mice. Int J Radiat Oncol Biol Phys. 1989;17:101–107
  75. Lefaix JL, Delanian S, Vozenin MC. Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and α-tocopherol: An experimental study. Int J Radiat Oncol Biol Phys. 1999;43:839–847
  76. Stelzer KJ, Koh WJ, Peterson LM. Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a rat lung perfusion model. Int J Radiat Oncol Biol Phys. 1996;34:111–115
  77. Delanian S, Balla-Mekias S, Lefaix JL. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol. 1999;17:3283–3290
  78. Kwon HC, Kim SK, Chung WK. Effect of pentoxifylline on radiation response of non-small cell lung cancer: A phase III randomized multicenter trial. Radiother Oncol. 2000;56:175–179
  79. Bianco JA, Appelbaum FR, Nemunaitis J. Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood. 1991;78:1205–1211
  80. Clift RA, Bianco JA, Appelbaum FR. A randomized controlled trial of pentoxifylline for the prevention of regimen-related toxicities in patients undergoing allogeneic marrow transplantation. Blood. 1993;82:2025–2030
  81. Ferrà C, de Sanjosé S, Lastra CF. Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. Bone Marrow Transplant. 1997;20:1075–1080
  82. Hornsey S, Myers R, Jenkinson T. The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs. Int J Radiat Oncol Biol Phys. 1990;18:1437–1442
  83. Hopewell JW, Robbins MEC, van den Aardweg GJMJ. The modulation of radiation-induced damage to pig skin by essential fatty acids. Br J Cancer. 1993;68:1–7
  84. Hopewell JW, van den Aardweg GJMJ, Morris GM. Amelioration of both early and late radiation-induced damage to pig skin by essential fatty acids. Int J Radiat Oncol Biol Phys. 1994;30:1119–1125
  85. Fike JR, Gobbel GT, Marton LJ. Radiation brain injury is reduced by the polyamine inhibitor α-difluoromethylornithine. Radiat Res. 1996;138:99–106
  86. Lefaix JL, Delanian S, Leplat JJ. Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: An experimental study. Int J Radiat Oncol Biol Phys. 1996;35:305–312
  87. Delanian S, Baillet F, Huart J. Successful treatment of radiation-induced fibrosis using liposomal Cu/Zn superoxide dismutase: Clinical trial. Radiother Oncol. 1994;32:12–20
  88. Epperly M, Bray J, Kraeger S. Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther. 1998;5:196–208
  89. Epperly MW, Kagan VE, Sikora CA. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. Int J Cancer. 2001;96:221–231
  90. Savla U, Waters CM. Barrier function of airway epithelium: Effects of radiation and protection by keratinocyte growth factor. Radiat Res. 1998;150:195–203
  91. Cohen EP, Juckett MB. Benefit of angiotensin antagonism in bone marrow transplant nephropathy. J Am Soc Nephrol. 1996;7:A1370
  92. National Council on Radiation Protection and Measurements . Management of terrorist events involving radioactive material (NCRP Report No. 138). Bethesda, MD 2001;
  93. Moulder JE. Multiorgan problems associated with total and partial body irradiation. In:  Ricks RC,  Berger ME,  O'Hara FM editor. The medical basis for radiation-accident preparedness: The clinical care of victims. New York, NY: The Parthenon Publishing Group; 2002;p. 175–189

 Supported in part by NIH grant CA-24652.

☆☆ Address reprint requests to John E. Moulder, PhD, Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226.

PII: S1053-4296(03)50010-8

doi: 10.1053/srao.2003.50007

Seminars in Radiation Oncology
Volume 13, Issue 1 , Pages 73-84 , January 2003