The anthracycline class of chemotherapy drugs still form the mainstay of management for many tumour types but, of course, the risk of cardiotoxicity is an important consideration when using anthracyclines. Having an agent like dexrazoxane that can serve as a cardioprotectant is very useful.
What about anthracyclines exhibiting cardiotoxicity, how does dexrazoxane fare?
The precise underlying mechanism of action of anthracycline cardiotoxicity is still not precisely defined. There are a few potential mechanisms of action and dexrazoxane currently is the only clinically proven cardioprotective agent against anthracycline cardiotoxicity.
What are the concerns around using anthracyclines and dexrazoxane? What has recent literature shown?
There are two major concerns, or two perceived major concerns, one being the potential interaction with the efficacy of chemotherapy. One of the randomised trials in breast cancer showed a statistically lower response rate in the patients treated with an anthracycline and dexrazoxane compared to those treated with an anthracycline alone. But that trial showed no difference in progression free or overall survival between the two arms and none of the other randomised trials have shown any significant difference in efficacy between patients treated with an anthracycline and dexrazoxane compared to those treated with an anthracycline alone.
The second perceived concern is the risk of secondary cancers following the use of dexrazoxane. A study was published a few years ago in the Journal of Clinical Oncology by Tebbi and colleagues suggesting that there may be a link between dexrazoxane use and secondary cancers. However, further analysis has suggested that this is not the case.
Would you advise using dexrazoxane?
I use the drug for patients who are being treated with an anthracycline, patients who are being retreated with an anthracycline. Again, these sorts of decisions are context dependent but I would fully support the geriatric oncologist in terms of considering using dexrazoxane for a patient at risk of anthracycline associated cardiotoxicity.
Do you have anything else to say about dexrazoxane?
It’s a drug that has been around for a long time. It’s a useful drug in terms of managing patients who are at risk of anthracycline associated cardiotoxicity. It is important that the communication is improved in terms of the perceived complications from the drug i.e. the perception that it interferes with chemotherapy efficacy and the perception that it is associated with an increased risk of secondary malignancies. Both of those have been shown to not be the case.