Dexrazoxane (Cardioxane): restriction of use
- Medicines and Healthcare products Regulatory Agency
- 6 July 2011
- Therapeutic area:
- Cancer and Haematology
Use restricted to adults with advanced or metastatic breast cancer only.
Article date: July 2011
Dexrazoxane (Cardioxane) is indicated for the prevention of chronic cumulative cardiotoxicity caused by doxorubicin or epirubicin in patients with advanced or metastatic cancer after previous anthracycline-containing treatment. An analogue of ethylene diamine-tetraacetic acid (EDTA), it is thought to reduce anthracycline-induced cardiotoxicity by chelation of free iron-containing cations. The drug is also an inhibitor of topoisomerase II and has cytotoxic properties. Most controlled clinical studies of dexrazoxane have been done in patients with advanced breast cancer.
Evidence of harm in children
Two randomised open studies reported a three-fold increase in the incidence of second primary malignancies (particularly acute myeloid leukaemia [AML] and myelodysplastic syndrome) in dexrazoxane-treated children compared with controls.1 2 A significantly increased risk of other toxicities compared with controls, including severe myelosuppression and severe infection, was also reported in one study. 3
Use in adults
Four post-marketing case reports of AML have been reported from France in adults with breast cancer. There is also evidence of increased myelosuppression in patients treated with dexrazoxane. Some studies have observed a higher incidence of death in groups treated with dexrazoxane plus chemotherapy compared with those given chemotherapy alone. The possibility that dexrazoxane was a contributing factor to this imbalance cannot be ruled out.
Furthermore, a significant decrease in tumour response rate has been reported in a study of patients with advanced breast cancer treated with doxorubicin and dexrazoxane compared with those treated with doxorubicin and placebo.4 Since both dexrazoxane and doxorubicin are topoisomerase inhibitors, it is possible that dexrazoxane may interfere with the antitumour efficacy of doxorubicin.
Advice for healthcare professionals:
- dexrazoxane is contraindicated for use in children and adolescents up to age 18 years
- use is restricted to adults with advanced or metastatic breast cancer
- use of dexrazoxane in combination with adjuvant breast cancer therapy or chemotherapy intended as curative is not recommended
- patients should be counselled about the risk of leukaemia
- patients with breast cancer should have received a cumulative dose of at least 300 mg/m2 doxorubicin or 540 mg/m2 epirubicin before starting dexrazoxane
- the dose ratio is now 10:1 for dexrazoxane:doxorubicin and for dexrazoxane:epirubicin
See website of the European Medicines Agency.
Article citation: Drug Safety Update July 2011, vol 4 issue 12: A3.
Published: 6 July 2011