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Treatment of anthracycline extravasation in mice with dexrazoxane with or without DMSO and hydrocortisone

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Abstract

Dexrazoxane has been reported to be protective against anthracycline induced subcutaneous ulceration in mice. It is currently under clinical investigation as an acute antidote in accidental anthracycline extravasation, for which indication topical dimethylsulfoxide (DMSO) and intralesional hydrocortisone are used empirically. We studied the effect in 72 mice of monotherapy with and combined therapy of intraperitoneal dexrazoxane, topical DMSO, and intralesional hydrocortisone as acute antidotes against ulceration after subcutaneous daunorubicin. Dexrazoxane completely prevented wounds from occurring, while neither DMSO nor hydrocortisone had any preventive effect. The addition of topical DMSO actually reduced the efficacy of dexrazoxane. In conclusion, the present study does not support the concomitant use of topical DMSO + systemic dexrazoxane or intralesional hydrocortisone + systemic dexrazoxane. Monotherapy with systemic dexrazoxane seems preferable and is highly efficacious in preventing ulceration.

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References

  1. Langer SW, Sehested M, Jensen PB (2000) Treatment of anthracycline extravasation with dexrazoxane. Clin Cancer Res 6:3680–3686

    PubMed  CAS  Google Scholar 

  2. Langer SW, Sehested M, Jensen PB (2001) Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. Ann Oncol 12:405–410

    Article  PubMed  CAS  Google Scholar 

  3. Langer SW, Sehested M, Jensen PB, Buter J, Giaccone G (2000) Dexrazoxane in anthracycline extravasation. J Clin Oncol 18:3064

    PubMed  CAS  Google Scholar 

  4. Jensen JN, Lock-Andersen J, Langer SW, Mejer J (2003) Dexrazoxane—a promising antidote in the treatment of accidental extravasation of anthracyclines. Scand J Plast Reconstr Surg Hand Surg 37:174–175

    Article  PubMed  Google Scholar 

  5. Bos AM, van der Graaf WT, Willemse PH (2001) A new conservative approach to extravasation of anthracyclines with dimethylsulfoxide and dexrazoxane. Acta Oncol 40:541–542

    Article  PubMed  CAS  Google Scholar 

  6. El Saghir N, Otrock Z, Mufarrij A, Abou-Mourad Y, Salem Z, Shamseddine A, Abbas J (2004) Dexrazoxane for anthracycline extravasation and GM-CSF for skin ulceration and wound healing. Lancet Oncol 5:320–321

    Article  PubMed  CAS  Google Scholar 

  7. Topotarget A/S, Copenhagen Denmark (2005) TT02—a clinical trial on Topotect® (dexrazoxane) in the treatment of accidental extravasation of anthracycline anti-cancer agents

  8. Bertelli G, Gozza A, Forno GB, Vidili MG, Silvestro S, Venturini M, Del Mastro L, Garrone O, Rosso R, Dini D (1995) Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study. J Clin Oncol 13:2851–2855

    PubMed  CAS  Google Scholar 

  9. The Council of Europe Convention, Strasbourg (1986) The Council of Europe Convention for the protection of vertebrate animals used for experimental and other scientific purposes, 18 March 1986

  10. Dorr RT, Alberts DS, Chen HS (1980) The limited role of corticosteroids in ameliorating experimental doxorubicin skin toxicity in the mouse. Cancer Chemother Pharmacol 5:17

    Article  PubMed  CAS  Google Scholar 

  11. Upton J, Mulliken JB, Murray JE (1979) Major intravenous extravasation injuries. Am J Surg 137:497–506

    Article  PubMed  CAS  Google Scholar 

  12. Loth TS, Eversmann WW Jr (1986) Treatment methods for extravasations of chemotherapeutic agents: a comparative study. J Hand Surg Am 11:388–396

    PubMed  CAS  Google Scholar 

  13. Coleman JJ III, Walker AP, Didolkar MS (1983) Treatment of adriamycin-induced skin ulcers: a prospective controlled study. J Surg Oncol 22:129–135

    Article  PubMed  CAS  Google Scholar 

  14. Cohen MH (1979) Amelioration of adriamycin skin necrosis: an experimental study. Cancer Treat Rep 63:1003–1004

    PubMed  CAS  Google Scholar 

  15. Soble MJ, Dorr RT, Plezia P, Breckenridge S (1987) Dose-dependent skin ulcers in mice treated with DNA binding antitumor antibiotics. Cancer Chemother Pharmacol 20:33–36

    Article  PubMed  CAS  Google Scholar 

  16. Dorr RT, Alberts DS (1983) Failure of DMSO and vitamin E to prevent doxorubicin skin ulceration in the mouse. Cancer Treat Rep 67:499–501

    PubMed  CAS  Google Scholar 

  17. Svingen BA, Powis G, Appel PL, Scott M (1981) Protection by alpha-tocopherol and dimethylsulfoxide (DMSO) against adriamycin induced skin ulcers in the rat. Res Commun Chem Pathol Pharmacol 32:189–192

    PubMed  CAS  Google Scholar 

  18. Desai MH, Teres D (1982) Prevention of doxorubicin-induced skin ulcers in the rat and pig with dimethyl sulfoxide (DMSO). Cancer Treat Rep 66:1371–1374

    PubMed  CAS  Google Scholar 

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Acknowledgements

We are indebted to Annette Nielsen for her expert technical support.

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Correspondence to Seppo W. Langer.

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Langer, S.W., Thougaard, A.V., Sehested, M. et al. Treatment of anthracycline extravasation in mice with dexrazoxane with or without DMSO and hydrocortisone. Cancer Chemother Pharmacol 57, 125–128 (2006). https://doi.org/10.1007/s00280-005-0022-7

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  • DOI: https://doi.org/10.1007/s00280-005-0022-7

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