Abstract
BackgroundContinuous infusion of doxorubicin or dexrazoxane pre-treatment prior to bolus doxorubicin are proven strategies to protect against doxorubicin-induced cardiotoxicity. Recently, global longitudinal peak systolic strain (GLS) measured with speckle tracking echocardiography (STE) and high-sensitivity troponin T (hs-TnT) have been validated as sensitive indicators of doxorubicin-induced cardiotoxicity. Here, we asked whether changes in hs-TnT and/or GLS can be detected in patients who were treated with continuous infusion of doxorubicin or pre-treated with dexrazoxane followed by bolus doxorubicin.MethodsTwenty-nine patients with newly diagnosed sarcoma were assigned to receive either 72-h doxorubicin infusion or dexrazoxane pre-treatment before bolus doxorubicin. Eight patients received dexrazoxane pre-treatment; eleven patients received continuous doxorubicin infusion; ten patients crossed over from continuous infusion to dexrazoxane. Bloods were collected for hs-TnT at baseline, 24 h or 72 h after initiation of doxorubicin treatment in each chemotherapy cycle. All blood samples were assayed in batch using hs-TnT kit from Roche diagnostics. 2D Echo and STE were performed before doxorubicin, after cycle 3, and at the end of chemotherapy.ResultsSeven patients in the cross-over group have at least one hs-TnT measurement between 5 ng/L to 10 ng/L during and after chemotherapy. Ten patients have at least one hs-TnT measurement above 10 ng/ml during and after chemotherapy (six in dexrazoxane group, three in continuous infusion group, one in cross-over group). The average hs-TnT level increases with each additional cycle of doxorubicin treatment. Eight patients had a more than 5% reduction in LVEF at the end of chemotherapy (four in dexrazoxane group, three in continuous infusion group, and one in cross-over group). Four out of these eight patients had a change of GLS by more than 15% (three in the dexrazoxane group).ConclusionElevation in hs-TnT levels were observed in more than 59% of patients who had received either continuous doxorubicin infusion or dexrazoxane pre-treatment before bolus doxorubicin. However, changes in LVEF and GLS were less frequently observed. Thus, continuous doxorubicin infusion or dexrazoxane pre-treatment do not completely ameliorate subclinical doxorubicin-induced cardiotoxicity as detected by more sensitive techniques.
Highlights
In the era of targeted therapy, anthracyclines are still commonly used for the treatment of sarcomas, breast carcinomas, leukemia, and lymphomas [1]
Since sarcoma patients typically received higher dose of doxorubicin as compared to breast cancer patients, doxorubicin is usually given as a 72-h continuous infusion or pre-treated with dexrazoxane to reduce the incidence of cardiotoxicity at the University of Texas MD Anderson Cancer Center
We prospectively investigated whether high-sensitivity troponin T (hs-TnT) assay and global longitudinal peak systolic strain (GLS) can detect subclinical myocardial damage induced by doxorubicin in sarcoma patients who were treated with cardio-protective measures against doxorubicin-induced cardiotoxicity
Summary
In the era of targeted therapy, anthracyclines are still commonly used for the treatment of sarcomas, breast carcinomas, leukemia, and lymphomas [1]. Continuous infusion appeared not to be efficacious in preventing doxorubicin-induced cardiotoxicity in children with acute lymphocytic leukemia [9]. Dexrazoxane, was found to be efficacious in reducing doxorubicin-induced cardiotoxicity [12, 13]. Recent literature suggests that dexrazoxane ameliorates doxorubicin-induced cardiotoxicity through a direct inhibition of topoisomerase 2b, not through its iron chelating activity [14, 15]. Dexrazoxane is the only FDA-approved therapy to protect against doxorubicin-induced cardiotoxicity in breast cancer patients. Since sarcoma patients typically received higher dose of doxorubicin as compared to breast cancer patients, doxorubicin is usually given as a 72-h continuous infusion or pre-treated with dexrazoxane to reduce the incidence of cardiotoxicity at the University of Texas MD Anderson Cancer Center. We asked whether changes in hsTnT and/or GLS can be detected in patients who were treated with continuous infusion of doxorubicin or pretreated with dexrazoxane followed by bolus doxorubicin
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