Year : 2010 | Volume
: 6 | Issue : 4 | Page : 573--574
Good clinical and cost outcomes using dexrazoxane to treat accidental epirubicin extravasation
Patricia Araque Arroyo, Ruth Ubago Perez, Maria Amalia Fernandez Feijoo, Miguel Angel Calleja Hernandez
Department of Pharmacy, Virgen de las Nieves University Hospital, Avenida de las Fuerzas Armadas, 2. Granada -180 12, Spain
Patricia Araque Arroyo
C/Ancha, 28. La Solana (Ciudad Real)-13240
A 75-year-old man diagnosed with lower esophageal adenocarcinoma suffered from epirubicin extravasation during the second cycle of neoadjuvant chemotherapy with epirubicin and oxaliplatin. A full recovery was achieved after treatment with dexrazoxane (Cardioxane® ). This is the first time in our hospital that extravasation of an anthracycline has been treated with dexrazoxane. We used Cardioxane® , approved for the prevention of anthracycline-induced cardiotoxicity, while Savene® is indicated for the treatment of anthracycline extravasation. The treatment was effective, and the selection of Cardioxane® (seven-fold cheaper than Savene® ) yielded a cost saving. Consequently, Cardioxane® has been included in our guidelines for anthracycline extravasation.
|How to cite this article:|
Arroyo PA, Perez RU, Feijoo MA, Hernandez MA. Good clinical and cost outcomes using dexrazoxane to treat accidental epirubicin extravasation.J Can Res Ther 2010;6:573-574
|How to cite this URL:|
Arroyo PA, Perez RU, Feijoo MA, Hernandez MA. Good clinical and cost outcomes using dexrazoxane to treat accidental epirubicin extravasation. J Can Res Ther [serial online] 2010 [cited 2022 May 20 ];6:573-574
Available from: https://www.cancerjournal.net/text.asp?2010/6/4/573/77081
Anthracycline extravasation has a reported incidence of 0.1 to 1% and can be devastating. , It progresses to ulceration in 25 to 50% of cases,  and most of these require surgery and subsequent skin graft. Dexrazoxane, a bisdioxopiperazine, has been the first drug authorized for use against the tissue destruction caused by anthracycline extravasation. Although its action mechanism has not been fully elucidated, it may be related to the manner in which it binds to body iron (chelation) and to its effect on certain enzymes (topoisomerase II, therapeutic target of anthracyclines).  Dexrazoxane per se does not possess antitumor activity; its main dose-limiting toxicity is myelosuppression.
Two presentations of dexrazoxane, Cardioxane® and Savene® , are available in Spain. Cardioxane® was authorized in March 2006 for the prevention of chronic cumulative cardiotoxicity associated with doxorubicin or epirubicin administration. One year later, Savene® was approved for the treatment of anthracycline extravasation. The presentation approved by the FDA for this indication is Totect® . The special relevance of our report is that Cardioxane® proved to be effective to treat the extravasation at one-seventh of the cost of Savene® . We present and discuss the first case in our hospital of the use of dexrazoxane for this purpose.
A 73-year-old man (body surface area of 2.17 m 2 ) diagnosed with lower-third esophageal adenocarcinoma (T3N0M0) was referred to the day hospital of our center for a second cycle of neoadjuvant chemotherapy (EOX regimen): epirubicin (75 mg/100 ml ClNa) plus oxaliplatin (195 mg/250 ml 5% SG). The extravasation was in the right antebrachial basilic vein after infusion of 50 to 75 ml of the epirubicin solution with a 22G catheter. Immediately after the accident, there was mild necrosis at the injection site, with pain and inflammation in the affected area (around 200 cm 2 ). Initial safety measures were as follows: aspiration by 10-ml syringe of the maximum amount of extravasated medicament through the intravenous access route, local application of cold, elevation of the affected limb, and a single topical application of 99% dimethyl sulfoxide (DMSO). The attending oncologist consulted with the Cytotoxic Unit of the Pharmacy Department about the possibility of using dexrazoxane. Because Savene® is not available at our center, we proposed the utilization of Cardioxane® . The patient signed his written consent to the off-label administration of this drug. After testing that his renal function was preserved (creatinine clearance of 95.74 ml/min), 1 000 mg/m 2 of Cardioxane® was infused (administration time of 1-2 hour) at 4 and 24 hours after the extravasation and 500 mg/m 2 was infused on day 3, as indicated in the data sheet;  the local cold was removed 15 minutes before infusions to ensure an adequate blood flow. After the dexrazoxane treatment, there was a mild erythema of 15 cm 2 (duration of 48 hours) and a slight swelling of the extravasated area, and the pain had disappeared. One month later, the patient continued with the originally programmed chemotherapy cycle. An exhaustive follow-up of hematologic variables was performed during the next two treatment cycles, but no additive toxic effects were detected.
At 90 days of follow-up, the patient's recovery was complete. No skin toxicity signs were observed and there was no hematologic toxicity.
In this case of anthracycline extravasation, the administration of dexrazoxane (Cardioxane® ) proved to be an effective and well-tolerated treatment.
Extravasations comprise 0.5 to 6% of the adverse effects associated with chemotherapy.  The severity of tissue damage is proportional to the amount and concentration of the drug infiltrating interstitial tissue; , it ranges from mild erythema, edema, and pain to severe tissue necrosis and ulceration involving neighboring structures (e.g., extensor tendons of the hand). Before the approval of Savene® , DMSO was probably the most widely used agent for this type of lesion, despite the lack of clinical evidence.  Authorization of dexrazoxane (Savene® ) for this indication was based on a study by Mouridsen et al. who conducted two trials in a total of 57 patients with the primary objective of preventing necrosis that would require surgery. No patients in the first trial and only one in the second trial needed surgery. No patient presented with grade IV adverse effects and no deaths were associated with the treatment. The efficacy of Savene® was also demonstrated in animal studies and case reports. 
We decided that Cardioxane® could be used in place of Savene® because they share the same chemical structure, as does Totect® . The products marketed in Europe, Cardioxane® and Savene® , only differ in reconstitution vehicle (sterile water for Savene® ;  0.16 M Ringer's lactate or sodium lactate for Cardioxane® ) and excipient composition (Savene® contains potassium and sodium and therefore requires stricter analytic control). Both contain 500 mg of active ingredient in the same form (dexrazoxane hydrochloride) and are intravenously infused.
It is well known that anthracycline extravasation requires urgent treatment, but the cost of this type of medicament is prohibitive for the large majority of health centers. In this respect, it is important to point out the considerable difference in the price of these drugs. At current prices in Spain, the use of Cardioxane® rather than the dexrazoxane specifically indicated for anthracycline extravasation yields a costs saving of 8 685€ per course of treatment.
This successful experience with Cardioxane® was presented to the hospital pharmacy and therapy committee, leading to its inclusion in our hospital guidelines for anthracycline extravasation. To avoid its excessive utilization, the extravasation must be considered severe by the attending oncologist. Moreover, this application must be strictly followed up, with the presentation of a case report to the pharmacy committee. The use of Cardioxane® rather than the specifically indicated dexrazoxane yields a major costs saving.
The authors are grateful to Richard Davies for assistance with the English version.
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