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Article

Totect™: A New Agent for Treating Anthracycline Extravasation

Lisa Schulmeister
CJON 2007, 11(3), 387-395 DOI: 10.1188/07.CJON.387-395

Anthracycline chemotherapy agents bind to DNA and cause cell death when they extravasate into healthy tissue. Although many approaches to managing extravasations have been studied and reported, data from two prospective clinical trials suggest that Totect™ (dexrazoxane for injection, TopoTarget USA, Inc.) is an effective anthracycline extravasation treatment. Only 1 of 54 patients with doxorubicin or epirubicin biopsy-confirmed extravasations treated with Totect developed tissue necrosis. Because nurses are on the forefront of extravasation prevention and management, they need to be knowledgeable about this new agent and how it is administered.

References 

Andoh, R., & Ishida, R. (1998). Catalytic inhibitors of DNA topoisomerase II. <i>Biochimica et Biophysica Acta</i>, 1400, 155-171.

Barden, G.A. (1980). Venous extravasation of doxorubicin HCl with secondary skin ulceration. <i>Southern Medical Journal</i>, 73, 1543-1544.

Bedford Laboratories. (2006). Dexrazoxane [Package insert]. Bedford, OH: Author.

Bowers, D.G., & Lynch, J.B. (1978). Adriamycin extravasation. <i>Plastic and Reconstructive Surgery</i>, 61, 86-92.

Cabriales, S., Bresnahan, J., Testa, D., Espina, B.M., Scadden, D.T., Ross, M., et al. (1998). Extravasation of liposomal daunorubicin in patients with AIDS-associated Kaposi's sarcoma: A report of four cases. <i>Oncology Nursing Forum</i>, 25, 67-70.

Comas, D., & Mateu, J. (1996). Treatment of extravasation of both doxorubicin and vincristine administration in a Y-site infusion. <i>Annals of Pharmacotherapy</i>, 30, 244-246.

Di Paolo, A. (2004). Liposomal anticancer therapy: Pharmacokinetic and clinical aspects. <i>Journal of Chemotherapy</i>, 16(Suppl. 4), 90-93.

Dorr, R.T., & Alberts, D.S. (1981). Pharmacologic antidotes to experimental doxorubicin skin toxicity: A suggested role for beta-adrenergic compounds. <i>Cancer Treatment Reports</i>, 65, 1001-1006.

El-Saghir, N.S., Mrad, A., Abbas, J., Mufarrij, A., Shamseddine, A., & Salem, Z. (2003). Dexrazoxane is an effective immediate therapy for doxorubicin extravasation [Abstract 580]. <i>Proceedings of the American Society of Clinical Oncology</i>, 22, 145.

Ener, R.A., Meglathery, S.B., & Styler, M. (2004). Extravasation of systemic hemato-oncological therapies. <i>Annals of Oncology</i>, 15, 858-862.

Frost, A., Gmehling, D., Azemar, M., Unger, C., & Mross, K. (2006). Treatment of anthracycline extravasation with dexrazoxane— Clinical experience. <i>Onkologie</i>, 29, 314-318.

Giaccone, G. (2006). <i>Successful treatment of anthracycline extravasation with Savene™ (dexrazoxane). Results from two multicenter prospective clinical studies</i>. Presentation at the 31st Congress of the European Society for Medical Oncology, Istanbul, Turkey. Retrieved December 7, 2006, from http://www.savene.com/multimedia/Giaccone_presentation_V2a.pdf

Goolsby, T.V., & Lombardo, F.A. (2006). Extravasation of chemotherapeutic agents: Prevention and treatment. <i>Seminars in Oncology</i>, 33, 139-143.

Hellmann, K. (1998). Overview and historical development of dexrazoxane. <i>Seminars in Oncology</i>, 25(Suppl. 10), 48-54.

Jenkins, J., & Corden, B.J. (1983). Vesicant activity of chemotherapeutic agents. <i>Cancer Treatment Reports</i>, 67, 409.

Jensen, J.N., Lock-Andersen, J., Langer, S.W., & Mejer, J. (2003). Dexrazoxane—A promising antidote in the treatment of accidental extravasation of anthracyclines. <i>Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery</i>, 37, 174-175.

Langer, S.W., Sehested, M., & Jensen, P.B. (1999). ICRF-187 (dexrazoxane) inhibits doxorubicin-induced S.C. necrosis in mice: A new strategy in treating accidental anthracycline extravasation [Abstract 695]. <i>Proceedings of the 35th Annual Meeting of the American Society of Clinical Oncology</i>, 18, 695.

Langer, S.W., Sehested, M., & Jensen, P.B. (2000a). Protection against anthracycline induced extravasation injuries with dexrazoxane: Elucidation of the possible mechanism. <i>Proceedings of the American Association for Cancer Research</i>, 41, 492.

Langer, S.W., Sehested, M., & Jensen, P.B. (2000b). Treatment of anthracycline extravasation with dexrazoxane. <i>Clinical Cancer Research</i>, 6, 3680-3686.

Langer, S.W., Sehested, M., & Jensen, P.B. (2001). Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. <i>Annals of Oncology</i>, 12, 405-410.

Langer, S.W., Sehested, M., Jensen, P.B., Buter, J., & Giaccone, G. (2000). Dexrazoxane in anthracycline extravasation. <i>Journal of Clinical Oncology</i>, 18, 3064.

Langer, S.W., Thougaard, A.V., Sehested, M., & Jensen, P.B. (2006). Treatment of anthracycline extravasation in mice with dexrazoxane with or without DMSO and hydrocortisone. <i>Cancer Chemotherapy and Pharmacology</i>, 57, 125-128.

Laughlin, R.A., Landeen, J.M., & Habal, M.B. (1979). The management of inadvertent subcutaneous adriamycin infiltration. <i>American Journal of Surgery</i>, 137, 408-412.

Lokich, J. (1999). Doxil extravasation injury: A case report. <i>Annals of Oncology</i>, 10, 735-736.

Luedke, D.W., Kennedy, P.S., & Rietschel, R.L. (1979). Histopathogenesis of skin and subcutaneous injury induced by adriamycin. <i>Plastic and Reconstructive Surgery</i>, 63, 463-465.

Mehta, P., & Najar, N. (1978). Skin ulceration due to faulty adriamycin administration. <i>Clinical Pediatrics</i>, 17, 663-664.

Mouridsen, H.T., Langer, S.W., Buter, J., Eidtmann, H., Rosti, G., de Wit, M., et al. (2006a). Successful treatment of anthracycline extravasation with Savene (dexrazoxane). Results from two prospective clinical multicenter studies [Abstract LBA9]. <i>Annals of Oncology</i>, 17(Suppl. 9). Retrieved December 5, 2006, from http://annonc.oxfordjournals.org/cgi/reprint/17/suppl_9/NP-a

Mouridsen, H.T., Langer, S.W., Buter, J., Eidtmann, H., Rosti, G., de Wit, M., et al. (2006b). Treatment of anthracycline extravasation with Savene (dexrazoxane). Results from two prospective clinical multicenter studies. <i>Annals of Oncology</i>, 18, 546-550.

Mross, K., van der Vijgh, W.J., Gall, H., Boven, E., & Pinedo, H.M. (1988). Pharmacokinetics and metabolism of epidoxorubicin and doxorubicin in humans. <i>Journal of Clinical Oncology</i>, 6, 517-526.

Pfizer, Inc. (2000). Zinecard® (dexrazoxane) [Package insert]. New York: Author.

Polovich, M., White, J.M., & Kelleher, L.O. (2005). <i>Chemotherapy and biotherapy guidelines and recommendations for practice</i> (2nd ed.). Pittsburgh, PA: Oncology Nursing Society.

Reilly, J.J., Neifeld, J.P., & Rosenberg, S.A. (1977). Clinical course and management of accidental adriamycin extravasation. <i>Cancer</i>, 40, 2053-2056.

Rudolph, R., Stein, R., & Pattillo, R. (1976). Skin ulcers due to adriamycin. <i>Cancer</i>, 38, 1087-1094.

Sauerland, C., Engelking, C., Wickham, R., & Corbi, D. (2006). Vesicant extravasation part I: Mechanisms, pathogenesis, and nursing care to reduce risk. <i>Oncology Nursing Forum</i>, 33, 1134-1141.

Schrijvers, D.L. (2003). Extravasation: A dreaded complication of chemotherapy. <i>Annals of Oncology</i>, 24(Suppl. 3), 26-30.

Schulmeister, L. (2005). Managing extravasations. <i>Clinical Journal of Oncology Nursing</i>, 9, 472-475.

Schulmeister, L., & Camp-Sorrell, D. (2000). Chemotherapy extravasation from implanted ports. <i>Oncology Nursing Forum</i>, 27, 531-538.

TopoTarget USA, Inc. (2007). Totect™ (dexrazoxane for injection) [Package insert]. Rockaway, NJ: Author.

Westlaw. (2006). Iris Molina and Melvin Molina v. Veronica Zaharia, MD, and "Jane Doe" [No. 2002 WL 32117311]. Stamford, CT: Author.

Wickham, R., Engelking, C., Sauerland, C., & Corbi, D. (2006). Vesicant extravasation part II: Evidence-based management and continuing controversies. <i>Oncology Nursing Forum</i>, 33, 1143-1150.