Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies

Mouridsen, H. T.
Langer, S. W.
Buter, J.
Eidtmann, H.
Rosti, G.
de Wit, M.
Knoblauch, P.
Rasmussen, A.
Dahlstrøm, K.
Jensen, P. B.
Giaccone, G.

¹Department of Oncology, Copenhagen University Hospital, Denmark
²Department of Medical Oncology, Free University, Amsterdam, The Netherlands
³Department of Obstetrics and Gynaecology, University Hospital Kiel, Kiel, Germany
⁴Department of Oncology and Haematology, Ravenna Public Hospital, Ravenna, Italy
⁵Department of Oncology and Haematology, University Hospital of Hamburg, Germany
⁶TopoTarget A/S, Symbion Science Park, Fruebjergvej, Copenhagen, Denmark
⁷Department of Plastic Surgery, Copenhagen University Hospital, Herlev, Denmark

Received 22 September 2006; revised 6 October 2006; accepted 9 October 2006

^*Correspondence to: Mrs L. Handskemager, TopoTarget A/S, Fruebjergvej 3, DK-2100 Copenhagen, Denmark. Tel: +45 39179495; Fax: +45 39178322; E-mail: [email protected]

Annals of Oncology 18(3):p 546-550, March 2007.

Background

The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene™ (EU), Totect™ (US)] as acute antidote in biopsy-verified anthracycline extravasation.

Patients and methods

Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m²) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months.

Results

In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site.

Conclusion

Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).