Langer_subbed.qxp 13/7/09 12:16 Page 26
Supportive Oncology
Finally, among the 27 remaining dexrazoxane-treated extravasations in
Seppo W Langer, MD, PhD, is a Consultant Medical
study TT01 and TT02 in which anthracycline extravasation was
Oncologist in the Department of Oncology at Copenhagen
suspected but not verified by biopsies, none progressed into ulceration.
University Hospital. He is a board-certified specialist in
internal medicine and medical oncology and holds a PhD
in pre-clinical studies of anthracycline extravasation.
A recent review of clinical cases with anthracycline extravasation
from central venous access devices also confirms the marked
efficacy of systemic antidotal treatment with dexrazoxane.
43
Maxwell Sehested, MD, PhD, is Chief Scienticfic Officer at
In September 2007, dexrazoxane was approved in the US by the US
TopoTarget and a Consultant Pathologist at Copenhagen
University Hospital. He is a board-certified pathologist with
Food and Drug Administration (FDA) under the brand name Totect for
a PhD in pre-clinical cancer therapeutics in the field of
the treatment of anthracycline extravasation, and the code 999.81 has multidrug resistance.
recently been added to the 2009 ICD-9-CM code system to describe
extravasation of vesicant chemotherapy.
44
Summary
Peter Buhl Jensen, MD, PhD, is Chief Executive Officer of
TopoTarget. He is an Honorary Professor of Oncology at
For 40 years of treatment with anthracycline-based chemotherapy,
the University of Copenhagen and a Consultant Medical
extravasation has been a feared complication. Dexrazoxane represents Oncologist at Copenhagen University Hospital. He is a
the first documented and licensed antidote against anthracycline
board-certified specialist in internal medicine and medical
oncology and holds a PhD in pre-clinical cancer
extravasation injuries. It is associated with a positive risk–benefit ratio
therapeutics evaluation.
and may prevent considerable morbidity in patients undergoing
anthracycline-based chemotherapy for cancer. ■
1. Schrijvers DL, Extravasation: a dreaded complication of solutions. Value of surgical emergency by aspiration and extravasation of cytostatic drugs by a conservative
chemotherapy, Ann Oncol, 2003;(Suppl. 3):26–30. lavage, Ann Chir Plast Esthet, 1997;42:305–13. approach, Cancer Chemother Pharmacol, 1992;30:330–33.
2. Reeves D, Management of anthracycline extravasation 18. Gault DT, Extravasation injuries, Br J Plast Surg, 1993;46:91–6. 33. Jensen PB, Sehested M, DNA topoisomerase II rescue by
injuries, Ann Pharmacother, 2007;41(7):1238–42. 19. Barlock AL, Howser DM, Hubbard SM, Nursing management catalytic inhibitors: a new strategy to improve the antitumor
3. Reilly JJ, Neifeld JP, Rosenberg SA, Clinical course and of adriamycin extravasation, Am J Nurs, 1979;79:94–6. selectivity of etoposide, Biochem Pharmacol, 1997;54(7):755–9.
management of accidental adriamycin extravasation, Cancer, 20. Harwood K, Gonin R, Long term vs long term cooling after 34. Schroeder PE, Hasinoff NN, The
1977;40:2053–6. doxorubicin (DOX) extravasation: An eastern cooperative doxorubicin-cardioprotective drug dexrazoxane undergoes
4. Larson DL, Treatment of tissue extravasation by antitumor group (ECOG) study, Proceed Am Soc Clin Oncol, 1994;13:447. metabolism in the rat to its metal ion-chelating form
agents, Cancer, 1982;49:1796–9. 21. Ludwig CU, Stoll HR, Obrist R, et al., Prevention of cytotoxic ADR-925, Cancer Chemother Pharmacol, 2002;50:509–13.
5. Preuss P, Partoft S, Cytostatic extravasations, Ann Plast Surg, drug induced skin ulcers with dimethyl sulfoxide (DMSO) 35. Langer SW, Sehested M, Jensen PB, Treatment of
1987;19:323–9. and alpha-tocopherole, Eur J Cancer Clin Oncol, 1987;23:327–9. anthracycline extravasation with dexrazoxane, Clin Cancer
6. Loth TS, Eversmann WWJ, Extravasation injuries in the upper 22. Olver IN, Schwarz MA, Use of dimethyl sulfoxide in limiting Res, 2000;6:3680–86.
extremity, Clin Orthop Relat Res, 1991;248–54. tissue damage caused by extravasation of doxorubicin, 36. Langer SW, Sehested M, Jensen PB, Dexrazoxane is a potent
7. Pitkänen J, Asko-Seljavaara S, Gröhn P, et al., Adriamycin Cancer Treat Rep, 1983;67:407–8. and specific inhibitor of anthracycline induced
extravasation: surgical treatment and possible prevention of 23. Olver IN, Aisner J, Hament A, et al., A prospective study of subcutaneous lesions in mice, Ann Oncol, 2001;12:405–10.
skin and soft-tissue injuries, J Surg Oncol, 1983;23:259–62. topical dimethyl sulfoxide for treating anthracycline 37. Langer SW, Thougaard AV, Sehested M, et al., Treatment of
8. Heitmann C, Durmus C, Ingianni G, Surgical management extravasation, J Clin Oncol, 1988;6:1732–5. anthracycline extravasation in mice with dexrazoxane with
after doxorubicin and epirubicin extravasation, J Hand Surg Br, 24. Lawrence HJ, Goodnight SHJ, Dimethyl sulfoxide and or without DMSO and hydrocortisone, Cancer Chemother
1998;23:666–8. extravasation of anthracycline agents, Ann Intern Med, 1983; Pharmacol, 2006;57:125–8.
9. Larson DL, What is the appropriate management of tissue 98:1025. 38. Langer SW, Sehested M, Jensen PB, et al., Dexrazoxane in
extravasation by antitumor agents?, Plast Reconstr Surg, 1985; 25. Lawrence HJ, Walsh D, Zapotowski KA, et al., Topical anthracycline extravasation, J Clin Oncol, 2000;18:3064.
75(3):397–402. dimethylsulfoxide may prevent tissue damage from 39. Bos AM, van der Graaf WT, Willemse PH, A new conservative
10. Langstein HN, Duman H, Seelig D, et al., Retrospective study anthracycline extravasation, Cancer Chemother Pharmacol, approach to extravasation of anthracyclines with
of the management of chemotherapeutic extravasation 1989;23:316–18. dimethylsulfoxide and dexrazoxane, Acta Oncol, 2001;40:
injury, Ann Plast Surg, 2002;49:369–74. 26. Bertelli G, Dini D, Forno G, et al., Dimethylsulphoxide and 541–2.
11. Tan C, Etcubanas E, Wollner N, et al., Adriamycin – an cooling after extravasation of antitumour agents, Lancet, 40. Jensen JN, Lock-Andersen J, Langer SW, et al.,
antitumor antibiotic in the treatment of neoplastic diseases, 1993;341:1098–9. Dexrazoxane-a promising antidote in the treatment of
Cancer, 1973;32:9–17. 27. Bertelli G, Gozza A, Forno GB, et al., Topical accidental extravasation of anthracyclines, Scand J Plast
12. Rudolph R, Stein RS, Pattillo RA, Skin ulcers due to dimethylsulfoxide for the prevention of soft tissue injury Reconstr Surg Hand Surg, 2003;37:174–5.
adriamycin, Cancer, 1976;38:1087–94. after extravasation of vesicant cytotoxic drugs: a 41. El-Saghir N, Otrock Z, Mufarrij A, et al., Dexrazoxane for
13. Schulmeister L, Managing vesicant extravasations, Oncologist, prospective clinical study, J Clin Oncol, 1995;13:2851–5. anthracycline extravasation and GM-CSF for skin ulceration
2008;13:284–8. 28. Bonnetblanc JM, Bordessoule D, Fayol J, et al., Treatment of and wound healing, Lancet Oncol, 2004;5:320–21.
14. Laughlin RA, Landeen JM, Habal MB, The management of accidental extravasation of antitumor agents with 42. Mouridsen HT, Langer SW, Buter J, et al., Treatment of
inadvertent subcutaneous adriamycin infiltration, Am J Surg, dimethylsulfoxide and alpha-tocopherol, Ann Dermatol anthracycline extravasation with Savene (dexrazoxane):
1979;137:408–12. Venereol, 1996;123:640–43. results from two prospective clinical multicentre studies,
15. Dahlstrøm KK, Chenoufi HL, Daugaard S, Fluorescence 29. Heckler FR, Current thoughts on extravasation injuries, Ann Oncol, 2007;18:546–50.
microscopic demonstration and demarcation of doxorubicin Clin Plast Surg, 1989;16:557-563. 43. Langer SW, Treatment of anthracycline extravasation from
extravasation. Experimental and clinical studies, Cancer, 30. Blair WF, Kilpatrick WCJ, Saiki JH, et al., Extravasation of centrally inserted venous catheters, Oncol Rev, 2008;2:
1990;65:1722–6. chemotherapeutic agents, Clin Orthop Relat Res, 1980;228–30. 114–16.
16. Andersson AP, Dahlstrøm KK, Clinical results after 31. Tsavaris NB, Karagiaouris P, Tzannou I, et al., A Conservative 44. Kane RC, McGuinn WDJ, Dagher R, et al., Dexrazoxane
doxorubicin extravasation treated with excision guided by approach to the treatment of chemotherapy-induced (Totect): FDA review and approval for the treatment of
fluorescence microscopy, Eur J Cancer, 1993;29A:1712–14. extravasation, J Dermatol Surg Oncol, 1990;16:519–22. accidental extravasation following intravenous anthracycline
17. Lambert F, Couturaud B, Arnaud E, et al., Iatrogenic 32. Tsavaris NB, Komitsopoulou P, Karagiaouris P, et al., chemotherapy, Oncologist, 2008;13:445–50.
extravasations of cytotoxic or hyperosmolar aqueous Prevention of tissue necrosis due to accidental
26 US ONCOLOGY
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100