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Dexrazoxane

Note: This section has health/medical information. It was not written by a health care professional. The medical references are: the journal articles listed below.

Dexrazoxane (sold under the brand name Zinecard® or Cardioxane®) has been studied as a heart protectant against the harmful effects of the anthracycline chemotherapy drugs (doxorubicin, daunorubicin, idarubicin). The consensus as of 2011 seems to be that it does protect the heart to some extent without compromising the effects of the chemotherapy. It is recommended sometimes, and usually only when the cumulative dose of anthracyclines is high, generally, greater than 300 mg/square meter.

Below are literature references and my brief comments.The Dana-Farber Cancer Institute would be the best place to start if you are interested in pursuing this treatment (Note the 2010 Lancet Oncology article below, lead author Steven Lipshultz.)


Cardioprotective interventions for cancer patients receiving anthracyclines. Van Dalen EC et al., Cochrane Database Syst Rev. 2011 Jun 15;(6). Abstract. a meta-review article of dexrazoxane use in adult cancer therapy. Briefly, dexrazoxane does not affect the success of cancer treatment and "if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines."


Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Steven E Lipshultz et al., The Lancet Oncology, Volume 11, Issue 10, Pages 950 - 961, October 2010. Abstract.

The article summarizes the dexrazoxane results of the Dana-Farber Cancer Institute trial, NCT00165087 (1996-2000). Dexrazoxane was only given to the high risk patients; these patients had a cumulative dose of 300 mg (per body surface area). A definite positive effect in long-term survival based on mean left ventricular fractional shortening and end-systolic dimension scores. "Interpretation Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys."


Older articles:

Cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review. Bryant J et al., Health Technol Assess. 2007 Jul;11(27):iii, ix-x, 1-84. Abstract. "It is difficult to draw conclusions about the effectiveness of technologies for reducing or preventing cardiotoxicity and about the use of cardiac markers in children as the evidence is limited in quantity and quality."

Topoisomerase IIß–Mediated DNA Double-Strand Breaks: Implications in Doxorubicin Cardiotoxicity and Prevention by Dexrazoxane. Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, Liu LF. Cancer Res. 2007 Sep 15;67(18):8839-46. PubMed Abstract.

Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Albert Moghrabi, et al. Blood. 2007 Feb 1;109(3):896-904. PubMed abstract. "We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) once-weekly Erwinia is less toxic than E coli asparaginase, but also less efficacious."

Dexrazoxane: a review of its use for cardioprotection during anthracycline chemotherapy. Cvetkovi RS, Scott LJ. Drugs. 2005;65(7):1005-24. Abstract. "At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data."

Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up. Elbl L et al., Support Care Cancer. 2006 Feb;14(2):128-36. Abstract. 108 patients studied for 2-20 years. Dexrazoxane lessened the risk of cardiac problems. The numbers are not huge, since only a percentage of the non-dexrazoxane group showed cardiac issues.

Dexrazoxane for the prevention of cardiomyopathy in anthracycline treated pediatric cancer patients. Anderson B. Pediatr Blood Cancer. 2005 Jun 15;44(7):584-8. Abstract.

Long-term serial echocardiographic examination of late anthracycline cardiotoxicity and its prevention by dexrazoxane in paediatric patients. Elbl L et al., Eur J Pediatr. 2005 Nov;164(11):678-84. Abstract. An eight year study of 75 patients. Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity.

The Effect of Dexrazoxane on Myocardial Injury in Doxorubicin-Treated Children with Acute Lymphoblastic Leukemia. Steven E. Lipshultz et al., N Engl J Med 2004; 351:145-153. Abstract. Dexrazoxane lessened the risk of high levels of serum cardiac troponin T during anthracycline treatment. The article does not follow to heart health or survival rate 4 years past treatment.

2003. The POG 9404 clinical trial for T-cell ALL included an arm that used dexrazoxane. In 2003, the dexrazoxane randomization results were reported. There was no difference in three year event free survival for patients treated with or without dexrazoxane. Dexrazoxane was used in the high-dose anthracycline treatment (over 275 or 300mg/square meter). (I could find no report of echocardiogram results or late effects of survivors with or without dexrazoxane.)

 

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