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Dexrazoxane protects the heart from the cumulative damage of doxorubicin in women with metastatic breast cancer who need to keep receiving it, and, as Totect, limits tissue destruction when an anthracycline leaks out of a vein.
Dexrazoxane (Zinecard) was approved in May 1995 to reduce the incidence and severity of doxorubicin cardiomyopathy in women with metastatic breast cancer who have received a cumulative 300 mg/m2 and will continue doxorubicin, on randomised trials that markedly reduced cardiac events; it is not used from the start of treatment because of an early signal of reduced response, later not confirmed. Totect was approved in 2007 for anthracycline extravasation, given within six hours on three consecutive days, on two single-arm European studies in which surgery was avoided in the great majority. Dexrazoxane is also used in paediatric leukaemia and lymphoma protocols to protect against late cardiotoxicity, an area where long-term Children's Oncology Group follow-up has been reassuring about secondary malignancy. Myelosuppression adds to that of chemotherapy.
Cyclic EDTA derivative hydrolysed intracellularly to a metal chelator that removes iron from anthracycline-iron complexes, limiting free-radical cardiac injury; also a catalytic topoisomerase II inhibitor, which underlies its action against extravasation injury.
1.Dexrazoxane slips into a pocket on its target.
Supportive Care: Prevention of cardiomyopathy associated with doxorubicin administration
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
Supportive Care: Prevention of cardiomyopathy associated with doxorubicin administration
Confirmed: the accelerated approval of 1995 converted to traditional approval 7.4 years after it was granted.
| Region | Year | Indication |
|---|---|---|
| US | 1995 | Reduction of doxorubicin cardiomyopathy in women with metastatic breast cancer after 300 mg/m2 cumulative dose (Zinecard) |
| US | 2007 | Anthracycline extravasation (Totect) |
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Query for this drug: (TITLE:"Dexrazoxane" OR ABSTRACT:"Dexrazoxane" OR TITLE:"Zinecard" OR ABSTRACT:"Zinecard" OR TITLE:"Totect" OR ABSTRACT:"Totect" OR TITLE:"Cardioxane" OR ABSTRACT:"Cardioxane" OR TITLE:"Savene" OR ABSTRACT:"Savene") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Dexrazoxane, not a curated reading list.
Shares Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards, Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first and the tag supportive.
Shares Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards, Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs and the tag supportive.
Shares Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards and the tag supportive.
Shares Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs and the tag supportive.
Shares Acute myeloid leukaemia in children, Acute lymphoblastic leukaemia and the tag supportive.
Shares Supportive care and survivorship roadmap: making treatment bearable → proving it extends life → caring for tens of millions afterwards and the tag supportive.
Shares Prevention of Anthracycline-Induced Cardiac Dysfunction With Dexrazoxane in Patients With Diffuse Large-B Cell Lymphoma and the tag supportive.
Shares Pfizer (incl. Seagen) and the tag supportive.