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Tissue repair in osteoradionecrosis using pentoxifylline and tocopherol—report of three cases

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Abstract

Purpose

Osteoradionecrosis is a complication of head and neck radiotherapy, with a difficult resolution and no well-established treatment. The disease progression can cause important loss on patient’s quality of life after cancer treatment. The options for treatment are limited and include clinical monitoring, prescription, or surgical procedures. As an alternative for bone necrosis treatment, a combination of drugs, pentoxifylline and tocopherol, can be used. Studies have shown that this combination significantly reduces chronic radiotherapy damage. The article reports successful treatment with this prescription protocol.

Methods

We report three cases of patients referred to the Service of Oral and Maxillofacial Surgery at Erasto Gaertner Hospital, in Curitiba, Brazil. They were submitted to radiotherapy for the treatment of malignant head and neck tumors and later developed osteoradionecrosis. They were treated with the combination pentoxifylline and tocopherol.

Results

All patients achieved complete remission in less than 1 year, with complete healing of bone exposure and without clinical symptoms.

Conclusions

This results show that this combination of drugs is beneficial in cases of bone necrosis induced by radiation, avoiding more aggressive treatments and reducing morbidity.

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References

  1. Almazrooa SA, Woo SB (2009) Bisphosphonate and nonbisphosphonate-associated osteonecrosis of the jaw: a review. J Am Dent Assoc 140(7):864–875

    Article  CAS  PubMed  Google Scholar 

  2. Marx RE (1983) Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 41(5):283–288

    Article  CAS  Google Scholar 

  3. Okunieff P, Augustine E, Hicks JE, Cornelison TL, Altemus RM, Naydich BG, Ding I, Huser AK, Abraham EH, Smith JJ, Coleman N, Gerber LH (2004) Pentoxifylline in the treatment of radiation-induced fibrosis. J Clin Oncol Off J Am Soc Clin Oncol 22(11):2207–2213. doi:10.1200/JCO.2004.09.101

    Article  CAS  Google Scholar 

  4. Delanian S, Lefaix JL (2002) Complete healing of severe osteoradionecrosis with treatment combining pentoxifylline, tocopherol and clodronate. Br J Radiol 75(893):467–469

    Article  CAS  PubMed  Google Scholar 

  5. Balogh JM, Sutherland SE (1989) Osteoradionecrosis of the mandible: a review. J Otolaryngol 18(5):245–250

    CAS  PubMed  Google Scholar 

  6. Delanian S, Lefaix JL (2004) The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol J Eur Soc Ther Radiol Oncol 73(2):119–131. doi:10.1016/j.radonc.2004.08.021

    Article  Google Scholar 

  7. Annane D, Depondt J, Aubert P, Villart M, Gehanno P, Gajdos P, Chevret S (2004) Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. J Clin Oncol Off J Am Soc Clin Oncol 22(24):4893–4900. doi:10.1200/JCO.2004.09.006

    Article  Google Scholar 

  8. Balazs C, Kiss E (1994) Immunological aspects of the effect of pentoxifylline (Trental) (a brief review). Acta Microbiol Immunol Hung 41(2):121–126

    CAS  PubMed  Google Scholar 

  9. Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (1999) Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. Am J Respir Crit Care Med 159(2):508–511. doi:10.1164/ajrccm.159.2.9804085

    Article  CAS  PubMed  Google Scholar 

  10. Berman B, Duncan MR (1989) Pentoxifylline inhibits normal human dermal fibroblast in vitro proliferation, collagen, glycosaminoglycan, and fibronectin production, and increases collagenase activity. J Invest Dermatol 92(4):605–610

    Article  CAS  PubMed  Google Scholar 

  11. Berman B, Duncan MR (1990) Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. Br J Dermatol 123(3):339–346

    Article  CAS  PubMed  Google Scholar 

  12. Lefaix JL, Delanian S, Vozenin MC, Leplat JJ, Tricaud Y, Martin M (1999) Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and alpha-tocopherol: an experimental study. Int J Radiat Oncol Biol Phys 43(4):839–847

    Article  CAS  PubMed  Google Scholar 

  13. Rudolph R, Vande Berg J, Schneider JA, Fisher JC, Poolman WL (1988) Slowed growth of cultured fibroblasts from human radiation wounds. Plast Reconstr Surg 82(4):669–677

    Article  CAS  PubMed  Google Scholar 

  14. Delanian S, Porcher R, Balla-Mekias S, Lefaix JL (2003) Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol Off J Am Soc Clin Oncol 21(13):2545–2550. doi:10.1200/JCO.2003.06.064

    Article  CAS  Google Scholar 

  15. Mandell GL (1995) Cytokines, phagocytes, and pentoxifylline. J Cardiovasc Pharmacol 25(Suppl 2):S20–S22

    Article  CAS  PubMed  Google Scholar 

  16. Delanian S, Lefaix JL (2007) Current management for late normal tissue injury: radiation-induced fibrosis and necrosis. Semin Radiat Oncol 17(2):99–107. doi:10.1016/j.semradonc.2006.11.006

    Article  PubMed  Google Scholar 

  17. McLeod NM, Pratt CA, Mellor TK, Brennan PA (2012) Pentoxifylline and tocopherol in the management of patients with osteoradionecrosis, the Portsmouth experience. Br J Oral Maxillofac Surg 50(1):41–44. doi:10.1016/j.bjoms.2010.11.017

    Article  CAS  PubMed  Google Scholar 

  18. Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein JN (1995) A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 33(1):99–109. doi:10.1016/0360-3016(95)00095-G

    Article  CAS  PubMed  Google Scholar 

  19. Silverman S., Jr. (1999) Oral cancer: complications of therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88 (2):122–126

    Article  PubMed  Google Scholar 

  20. Wahl MJ (2006) Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys 64(3):661–669. doi:10.1016/j.ijrobp.2005.10.021

    Article  PubMed  Google Scholar 

  21. Thorn JJ, Hansen HS, Specht L, Bastholt L (2000) Osteoradionecrosis of the jaws: clinical characteristics and relation to the field of irradiation. J Oral Maxillofac Surg 58(10):1088–1093 discussion 1093–1085. doi:10.1053/joms.2000.9562

    Article  CAS  PubMed  Google Scholar 

  22. Specht L (2002) Oral complications in the head and neck radiation patient. Introduction and scope of the problem. Support Care Cancer 10(1):36–39

    Article  PubMed  Google Scholar 

  23. Cheng SJ, Lee JJ, Ting LL, Tseng IY, Chang HH, Chen HM, Kuo YS, Hahn LJ, Kok SH (2006) A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys 64(1):90–97. doi:10.1016/j.ijrobp.2005.06.021

    Article  PubMed  Google Scholar 

  24. Schwartz HC, Kagan AR (2002) Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin Oncol 25(2):168–171

    Article  PubMed  Google Scholar 

  25. Mendenhall WM (2004) Mandibular osteoradionecrosis. J Clin Oncol Off J Am Soc Clin Oncol 22(24):4867–4868. doi:10.1200/JCO.2004.09.959

    Article  Google Scholar 

  26. Rothwell BR (1987) Prevention and treatment of the orofacial complications of radiotherapy. J Am Dent Assoc 114(3):316–322

    Article  CAS  PubMed  Google Scholar 

  27. Epstein JB, Rea G, Wong FL, Spinelli J, Stevenson-Moore P (1987) Osteonecrosis: study of the relationship of dental extractions in patients receiving radiotherapy. Head Neck Surg 10(1):48–54

    Article  CAS  PubMed  Google Scholar 

  28. Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL (2011) Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys 80(3):832–839. doi:10.1016/j.ijrobp.2010.03.029

    Article  PubMed  Google Scholar 

  29. Williamson R, Kondziolka D, Kanaan H, Lunsford LD, Flickinger JC (2008) Adverse radiation effects after radiosurgery may benefit from oral vitamin E and pentoxifylline therapy: a pilot study. Stereotact Funct Neurosurg 86(6):359–366. doi:10.1159/000163557

    Article  PubMed  Google Scholar 

  30. Robard L, Louis MY, Blanchard D, Babin E, Delanian S (2014) Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis 131(6):333–338. doi:10.1016/j.anorl.2013.11.006

    Article  CAS  PubMed  Google Scholar 

  31. Rice N, Polyzois I, Ekanayake K, Omer O, Stassen LF (2015) The management of osteoradionecrosis of the jaws—a review. Surgeon 13(2):101–109. doi:10.1016/j.surge.2014.07.003

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Erasto Gaertner Hospital, Rua Dr. Ovande do Amaral, 201, Curitiba, PR, 81520-060, Brazil

    Joslei Carlos Bohn, Juliana Lucena Schussel, Roberta Targa Stramandinoli-Zanicotti & Laurindo Moacir Sassi

  2. Graduate Program in Dentistry, Department of Stomatology, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Juliana Lucena Schussel

Authors
  1. Joslei Carlos Bohn
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  2. Juliana Lucena Schussel
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  3. Roberta Targa Stramandinoli-Zanicotti
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  4. Laurindo Moacir Sassi
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Correspondence to Juliana Lucena Schussel.

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Bohn, J.C., Schussel, J.L., Stramandinoli-Zanicotti, R.T. et al. Tissue repair in osteoradionecrosis using pentoxifylline and tocopherol—report of three cases. Oral Maxillofac Surg 20, 97–101 (2016). https://doi.org/10.1007/s10006-015-0522-5

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  • DOI: https://doi.org/10.1007/s10006-015-0522-5

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