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The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

Year 2012, , 32 - 38, 01.01.2012
https://doi.org/10.5152/balkanmedj.2011.005

Abstract

Objective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration. Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT), irradiation alone (RT), intraperitoneal amifostine plus irradiation (IPAMI), and intrarectal amifostine plus irradiation (IRAMI). The rats in the RT, IPAMI and IRAMI groups were irradiated individually with a single dose of 17.5 Gy to the pelvis. Amifostine was administered by the intraperitoneal (200 mg/kg) or intrarectal (2000 mg/kg) route before irradiation. Histopathologic analysis of the rectum was performed 14 days after irradiation. Results: Significant radiation damage appeared in all histopathologic parameters and was reduced by amifostine. Pretreatment with IPAMI significantly reduced the inflammatory infiltrate in the lamina propria (p=0.021), cryptitis (p=0.002) and crypt abscess (p=0.015). However, the protective effect of IRAMI was significant for all parameters with equal or higher significance than IPAMI, including the eosinophil leucocytes count (p=0.02), and distortion of the crypts (p=0.008), and was also significant for regenerative/reparative atypia (p=0.013). Conclusion: Intrarectal high dose topical administration of amifostine is more effective in the prevention of radiation-induced proctitis compared to its intraperitoneal systemic administration. Turkish Başlık: Radyasyon Kaynaklı Proktitte Amifostinin Koruyucu Etkinliği: Sistemik İle Topikal Uygulamaların Karşılaştırılması Anahtar Kelimeler: Amifostin, proktit, ışınlama, radyoproteksiyon Amaç: Bu çalışmanın amacı ışınlama ile oluşturulan proktitte amifostinin radyoprotektif etkinliğinin intrarektal ve intraperitoneal uygulama yapılarak karşılaştırılmasıdır. Hastalar ve Yöntemler: Otuz iki Sprague-Dawley sıçan randomize olarak 4 gruba ayrıldı: Kontrol (CONT), sadece ışınlama (RT), intraperitoneal amifostin ve ışınlama (IPAMI) ile intrarektal amifostin ve ışınlama (IRAMI). RT, IPAMI ve IRAMI gruplarındaki sıçanların her birinin pelvis bölgesi tek fraksiyonda 17,5 Gy ışınlandı. Amifostin ışınlamadan önce intraperitoneal (200 mg/kg) veya intrarektal (2000 mg/kg) yoldan uygulandı. Rektumun histopatolojik incelemesi ışınlamadan 14 gün sonra yapıldı. Bulgular: Bütün histopatolojik parametrelerde ışınlamanın istatistiksel olarak anlamlı hasar oluşturduğu ve bu hasarın amifostin uygulaması ile azaldığı gözlendi. Işınlamadan önce IPAMI uygulaması lamina propria inflamasyonunu (p=0.021), kriptiti (p=0.002), kript absesini (p=0.015) anlamlı olarak azalttı. Buna karşın IRAMI ile koruyucu etki eozinofil lökosit sayısı (p=0.02), kript distorsiyonu (p=0.013) ve rejeneratif/reperatif atipi (p=0.013) dahil tüm parametreler için anlamlı oldu ve anlamlılıkları IPAMI'ya göre eşit veya daha yüksekti. Sonuç: Amifostinin yüksek doz intrarektal topikal uygulaması ışınlamanın oluşturduğu proktitin önlenmesinde intraperitoneal sistemik uygulamasına göre daha etkindir. Anahtar sözcükler: Amifostin, proktit, ışınlama, radyoproteksiyon.

References

  • Zimmermann FB, Feldmann HJ. Radiation proctitis. Clinical and pathological manifestations, therapy and prophylaxis of acute and late injurious effects of radiation on the rectal mucosa. Strahlenther Onkol 1998;174 Suppl 3:85-9.
  • Hong JJ, Park W, Ehrenpreis ED. Review article: current thera- peutic options for radiation proctopathy. Aliment Pharmacol Ther 2001;15:1253-62. [CrossRef]
  • Lundby L, Overgaard J, Laurberg S. Histopathological and mor- phometric analyses of late rectal injury after irradiation. APMIS 2000;108:216-22. [CrossRef]
  • Dubray BM, Thames HD. Chronic radiation damage in the rat rectum: an analysis of the influences of fractionation, time and volume. Radiother Oncol 1994;33:41-7. [CrossRef]
  • Wang CJ, Leung SW, Chen HC, Sun LM, Fang FM, Huang EY, et al. The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: evidence suggestive of consequential late effect (CQLE). Int J Radiat Oncol Biol Phys 1998;40:85-91. [CrossRef]
  • Korkut C, Asoglu O, Aksoy M, Kapran Y, Bilge H, Kiremit-Korkut N, et al. Histopathological comparison of topical therapy modali- ties for acute radiation proctitis in an experimental rat model. World J Gastroenterol 2006;12:4879-83.
  • Sanguineti G, Franzone P, Marcenaro M, Foppiano F, Vitale V. Su- cralfate versus mesalazine versus hydrocortisone in the preven- tion of acute radiation proctitis during conformal radiotherapy for prostate carcinoma, A Randomized Study. Strahlenther Onkol 2003;179:464-70.
  • Kouloulias VE, Kouvaris JR, Pissakas G, Kokakis JD, Antypas C, Mal- las E, et al. A phase ii randomized study of topical intrarectal admin- istration of amifostine for the prevention of acute radiation-induced rectal toxicity. Strahlenther Onkol 2004;180:557-62 [CrossRef].
  • Kouloulias VE, Kouvaris JR, Pissakas G, Mallas E, Antypas C, Ko- kakis JD, et al. Phase II multicenter randomized study of ami- fostine for prevention of acute radiation rectal toxicity: topical intrarectal versus subcutaneous application. Int J Radiat Oncol Biol Phys 2005;62:486-93. [CrossRef]
  • Kouvaris J, Kouloulias V, Malas E, Antypas C, Kokakis J, Micho- poulos S, et al. Amifostine as radioprotective agent for the rectal mucosa during irradiation of pelvic tumors. A phase II random- ized study using various toxicity scales and rectosigmoidoscopy. Strahlenther Onkol 2003;179:167-74.
  • Damron TA, Spadaro JA, Tamurian RM, Damron LA. Sparing of radiation-induced damage to the physis: Fractionation alone compared to amifostine pretreatment. Int J Radiat Oncol Biol Phys 2000;47:1067-71. [CrossRef]
  • Eifel PJ, Levenback C, Wharton JT, Oswald MJ. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1995;32:1289-300. [CrossRef]
  • Wang J, Zheng H, Sung CC, Hauer-Jensen M. The synthetic somatostatin analogue, octreotide, ameliorates acute and de- layed intestinal radiation injury. Int J Radiat Oncol Biol Phys 1999;45:1289-96. [CrossRef]
  • Hauer-Jensen M, Poulakos L, Osborne JW. Effects of accelerated fractionation on radiation injury of the small intestine: a new rat model. Int J Radiat Oncol Biol Phys 1988;14:1205-12. [CrossRef]
  • Langberg CW, Sauer T, Reitan JB, Hauer-Jensen M. Tolerance of rat small intestine to localized single dose and fractionated irra- diation. Acta Oncol 1992;31:781-7. [CrossRef]
  • Sharma B, Pandey D, Chauhan V, Gupta D, Mokta J, Thakur SS. Radiation proctitis. Journal Indian Academy of Clinical Medicine 2005;6:146-51.
  • Sedgwick DM, Howard GC, Ferguson A. Pathogenesis of acute radiation injury to the rectum. A prospective study in patients. Int J Colorectal Dis 1994;9:23-30. [CrossRef]
  • Pía de la Maza M, Gotteland M, Ramírez C, Araya M, Yudin T, Bu- nout D, et al. Acute nutritional and intestinal changes after pelvic radiation. J Am Coll Nutr 2001;20:637-42.
  • Parks DA, Bulkley GB, Granger DN. Role of oxygen-derived free radicals in digestive tract diseases. Surgery 1983;94:415-22.
  • Hovdenak N, Fajardo LF, Hauer-Jensen M. Acute radiation proc- titis: a sequential clinicopathologic study during pelvic radiother- apy. Int J Radiat Oncol Biol Phys 2000;48:1111-7. [CrossRef]
  • Hensley ML, Schuchter LM, Lindley C, Meropol NJ, Cohen GI, Broder G, et al. American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiothera- py protectants. J Clin Oncol 1999;17:3333-55.
  • Ben-Josef E, Mesina J, Shaw LM, Bonner HS, Shamsa F, Porter AT. Topical application of WR-2721 achieves high concentrations in the rectal wall. Radiat Res 1995;143:107-10. [CrossRef]
  • Ben-Josef E, Han S, Tobi M, Shaw LM, Bonner HS, Vargas BJ, et al. A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury. Int J Radiat Oncol Biol Phys 2002;53:1160-4. [CrossRef]
  • France HG Jr, Jirtle RL, Mansbach CM 2nd. Intracolonic WR 2721 protection of the rat colon from acute radiation injury. Gastroen- terology 1986;91:644-50.
  • Ito H, Meistrich ML, Barkley HT Jr, Thames HD Jr, Milas L. Protection of acute and late radiation damage of the gastrointestinal tract by WR-2721. Int J Radiat Oncol Biol Phys 1986;12:211-9. [CrossRef]
  • Katsanos KH, Briasoulis E, Tsekeris P, Batistatou A, Bai M, Tolis C, et al. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis. J Exp Clin Cancer Res 2010;29:68. [CrossRef]
  • Montana GS, Anscher MS, Mansbach CM 2nd, Daly N, Delannes M, Carke-Pearson D, et al. Topical application of WR-2721 to pre- vent radiation-induced proctosigmoiditis. A phase I/II trial. Can- cer 1992;69:2826-30. [CrossRef]
  • Singh AK, Menard C, Guion P, Simone NL, Smith S, Crouse NS, et al. Intrarectal amifostine suspension may protect against acute proctitis during radiation therapy for prostate cancer: a pilot study. Int J Radiat Oncol Biol Phys 2006;65:1008-13. [CrossRef]
  • Simone NL, Menard C, Soule BP, Albert PS, Guion P, Smith S, et al. Intrarectal amifostine during external beam radiation therapy for prostate cancer produces significant improvements in Qual- ity of Life measured by EPIC score. Int J Radiat Oncol Biol Phys 2008;70:90-5. [CrossRef]
  • Trier JS, Browning TH. Morphologic response of the mu- cosa of human small intestine to x-ray exposure. J Clin Invest 1966;45:194-204. [CrossRef]
  • Fischer L, Kimose HH, Spjeldnaes N, Wara P. Late progress of radiation-induced proctitis. Acta Chir Scand 1990;156:801-5.

The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

Year 2012, , 32 - 38, 01.01.2012
https://doi.org/10.5152/balkanmedj.2011.005

Abstract

References

  • Zimmermann FB, Feldmann HJ. Radiation proctitis. Clinical and pathological manifestations, therapy and prophylaxis of acute and late injurious effects of radiation on the rectal mucosa. Strahlenther Onkol 1998;174 Suppl 3:85-9.
  • Hong JJ, Park W, Ehrenpreis ED. Review article: current thera- peutic options for radiation proctopathy. Aliment Pharmacol Ther 2001;15:1253-62. [CrossRef]
  • Lundby L, Overgaard J, Laurberg S. Histopathological and mor- phometric analyses of late rectal injury after irradiation. APMIS 2000;108:216-22. [CrossRef]
  • Dubray BM, Thames HD. Chronic radiation damage in the rat rectum: an analysis of the influences of fractionation, time and volume. Radiother Oncol 1994;33:41-7. [CrossRef]
  • Wang CJ, Leung SW, Chen HC, Sun LM, Fang FM, Huang EY, et al. The correlation of acute toxicity and late rectal injury in radiotherapy for cervical carcinoma: evidence suggestive of consequential late effect (CQLE). Int J Radiat Oncol Biol Phys 1998;40:85-91. [CrossRef]
  • Korkut C, Asoglu O, Aksoy M, Kapran Y, Bilge H, Kiremit-Korkut N, et al. Histopathological comparison of topical therapy modali- ties for acute radiation proctitis in an experimental rat model. World J Gastroenterol 2006;12:4879-83.
  • Sanguineti G, Franzone P, Marcenaro M, Foppiano F, Vitale V. Su- cralfate versus mesalazine versus hydrocortisone in the preven- tion of acute radiation proctitis during conformal radiotherapy for prostate carcinoma, A Randomized Study. Strahlenther Onkol 2003;179:464-70.
  • Kouloulias VE, Kouvaris JR, Pissakas G, Kokakis JD, Antypas C, Mal- las E, et al. A phase ii randomized study of topical intrarectal admin- istration of amifostine for the prevention of acute radiation-induced rectal toxicity. Strahlenther Onkol 2004;180:557-62 [CrossRef].
  • Kouloulias VE, Kouvaris JR, Pissakas G, Mallas E, Antypas C, Ko- kakis JD, et al. Phase II multicenter randomized study of ami- fostine for prevention of acute radiation rectal toxicity: topical intrarectal versus subcutaneous application. Int J Radiat Oncol Biol Phys 2005;62:486-93. [CrossRef]
  • Kouvaris J, Kouloulias V, Malas E, Antypas C, Kokakis J, Micho- poulos S, et al. Amifostine as radioprotective agent for the rectal mucosa during irradiation of pelvic tumors. A phase II random- ized study using various toxicity scales and rectosigmoidoscopy. Strahlenther Onkol 2003;179:167-74.
  • Damron TA, Spadaro JA, Tamurian RM, Damron LA. Sparing of radiation-induced damage to the physis: Fractionation alone compared to amifostine pretreatment. Int J Radiat Oncol Biol Phys 2000;47:1067-71. [CrossRef]
  • Eifel PJ, Levenback C, Wharton JT, Oswald MJ. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1995;32:1289-300. [CrossRef]
  • Wang J, Zheng H, Sung CC, Hauer-Jensen M. The synthetic somatostatin analogue, octreotide, ameliorates acute and de- layed intestinal radiation injury. Int J Radiat Oncol Biol Phys 1999;45:1289-96. [CrossRef]
  • Hauer-Jensen M, Poulakos L, Osborne JW. Effects of accelerated fractionation on radiation injury of the small intestine: a new rat model. Int J Radiat Oncol Biol Phys 1988;14:1205-12. [CrossRef]
  • Langberg CW, Sauer T, Reitan JB, Hauer-Jensen M. Tolerance of rat small intestine to localized single dose and fractionated irra- diation. Acta Oncol 1992;31:781-7. [CrossRef]
  • Sharma B, Pandey D, Chauhan V, Gupta D, Mokta J, Thakur SS. Radiation proctitis. Journal Indian Academy of Clinical Medicine 2005;6:146-51.
  • Sedgwick DM, Howard GC, Ferguson A. Pathogenesis of acute radiation injury to the rectum. A prospective study in patients. Int J Colorectal Dis 1994;9:23-30. [CrossRef]
  • Pía de la Maza M, Gotteland M, Ramírez C, Araya M, Yudin T, Bu- nout D, et al. Acute nutritional and intestinal changes after pelvic radiation. J Am Coll Nutr 2001;20:637-42.
  • Parks DA, Bulkley GB, Granger DN. Role of oxygen-derived free radicals in digestive tract diseases. Surgery 1983;94:415-22.
  • Hovdenak N, Fajardo LF, Hauer-Jensen M. Acute radiation proc- titis: a sequential clinicopathologic study during pelvic radiother- apy. Int J Radiat Oncol Biol Phys 2000;48:1111-7. [CrossRef]
  • Hensley ML, Schuchter LM, Lindley C, Meropol NJ, Cohen GI, Broder G, et al. American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiothera- py protectants. J Clin Oncol 1999;17:3333-55.
  • Ben-Josef E, Mesina J, Shaw LM, Bonner HS, Shamsa F, Porter AT. Topical application of WR-2721 achieves high concentrations in the rectal wall. Radiat Res 1995;143:107-10. [CrossRef]
  • Ben-Josef E, Han S, Tobi M, Shaw LM, Bonner HS, Vargas BJ, et al. A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury. Int J Radiat Oncol Biol Phys 2002;53:1160-4. [CrossRef]
  • France HG Jr, Jirtle RL, Mansbach CM 2nd. Intracolonic WR 2721 protection of the rat colon from acute radiation injury. Gastroen- terology 1986;91:644-50.
  • Ito H, Meistrich ML, Barkley HT Jr, Thames HD Jr, Milas L. Protection of acute and late radiation damage of the gastrointestinal tract by WR-2721. Int J Radiat Oncol Biol Phys 1986;12:211-9. [CrossRef]
  • Katsanos KH, Briasoulis E, Tsekeris P, Batistatou A, Bai M, Tolis C, et al. Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis. J Exp Clin Cancer Res 2010;29:68. [CrossRef]
  • Montana GS, Anscher MS, Mansbach CM 2nd, Daly N, Delannes M, Carke-Pearson D, et al. Topical application of WR-2721 to pre- vent radiation-induced proctosigmoiditis. A phase I/II trial. Can- cer 1992;69:2826-30. [CrossRef]
  • Singh AK, Menard C, Guion P, Simone NL, Smith S, Crouse NS, et al. Intrarectal amifostine suspension may protect against acute proctitis during radiation therapy for prostate cancer: a pilot study. Int J Radiat Oncol Biol Phys 2006;65:1008-13. [CrossRef]
  • Simone NL, Menard C, Soule BP, Albert PS, Guion P, Smith S, et al. Intrarectal amifostine during external beam radiation therapy for prostate cancer produces significant improvements in Qual- ity of Life measured by EPIC score. Int J Radiat Oncol Biol Phys 2008;70:90-5. [CrossRef]
  • Trier JS, Browning TH. Morphologic response of the mu- cosa of human small intestine to x-ray exposure. J Clin Invest 1966;45:194-204. [CrossRef]
  • Fischer L, Kimose HH, Spjeldnaes N, Wara P. Late progress of radiation-induced proctitis. Acta Chir Scand 1990;156:801-5.
There are 31 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Cem Uzal This is me

Ruşen Coşar Alas This is me

Atakan Sezer This is me

Ufuk Usta This is me

Necdet Süt This is me

Alaattin Özen This is me

Mehmet Ali Yağcı This is me

Publication Date January 1, 2012
Published in Issue Year 2012

Cite

APA Uzal, C., Alas, R. C., Sezer, A., Usta, U., et al. (2012). The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application. Balkan Medical Journal, 2012(1), 32-38. https://doi.org/10.5152/balkanmedj.2011.005
AMA Uzal C, Alas RC, Sezer A, Usta U, Süt N, Özen A, Yağcı MA. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application. Balkan Medical Journal. January 2012;2012(1):32-38. doi:10.5152/balkanmedj.2011.005
Chicago Uzal, Cem, Ruşen Coşar Alas, Atakan Sezer, Ufuk Usta, Necdet Süt, Alaattin Özen, and Mehmet Ali Yağcı. “The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application”. Balkan Medical Journal 2012, no. 1 (January 2012): 32-38. https://doi.org/10.5152/balkanmedj.2011.005.
EndNote Uzal C, Alas RC, Sezer A, Usta U, Süt N, Özen A, Yağcı MA (January 1, 2012) The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application. Balkan Medical Journal 2012 1 32–38.
IEEE C. Uzal, R. C. Alas, A. Sezer, U. Usta, N. Süt, A. Özen, and M. A. Yağcı, “The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application”, Balkan Medical Journal, vol. 2012, no. 1, pp. 32–38, 2012, doi: 10.5152/balkanmedj.2011.005.
ISNAD Uzal, Cem et al. “The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application”. Balkan Medical Journal 2012/1 (January 2012), 32-38. https://doi.org/10.5152/balkanmedj.2011.005.
JAMA Uzal C, Alas RC, Sezer A, Usta U, Süt N, Özen A, Yağcı MA. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application. Balkan Medical Journal. 2012;2012:32–38.
MLA Uzal, Cem et al. “The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application”. Balkan Medical Journal, vol. 2012, no. 1, 2012, pp. 32-38, doi:10.5152/balkanmedj.2011.005.
Vancouver Uzal C, Alas RC, Sezer A, Usta U, Süt N, Özen A, Yağcı MA. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application. Balkan Medical Journal. 2012;2012(1):32-8.