Abstract
BackgroundAnthracyclines, as the most effective therapy, are the cornerstone of advanced stage sarcoma treatment. However, anthracyclines can also contribute to myocardial dysfunction and congestive heart failure, ultimately limiting the therapeutic potential of the drug. Coadministration of Dexrazoxane has been shown to effectively reduce cardiotoxicity, however primarily in patients suffering in diseases other than sarcoma.MethodsThe aim of this retrospective analysis was to evaluate safety and efficacy of chemotherapy with high cumulative doses of anthracyclines in combination with Dexrazoxane. The medical charts of 32 patients treated in four institutions were analyzed. Reasons for coadministration were rechallenge, reaching the cumulative anthracycline dose and preexisting heart failure.ResultsThe median age was 54 years [18–68 years]. The median cumulative anthracycline dose before adding DRZ was 450 mg/m2 and after administration of last anthracycline containing therapy 750 mg/m2. Either during treatment or follow up, 2/27 patients (7 %) without preexisting major cardiac findings developed anthracycline-induced cardiotoxicity. The median overall survival (OS) from start of the first anthracycline containing chemotherapy was 46 months and 17 months from the initial coadministration of DRZ. At rechallenge, the median progression free survival (PFS) with DRZ was 7 months. In continuous therapy, the median PFS was 13 months from beginning of chemotherapy and 9 months from the addition of DRZ.ConclusionChemotherapy with high cumulative doses of anthracyclines in addition with DRZ demonstrated a remarkable OS in these advanced disease patients. Cardiac side-effects due to high cumulative doses of anthracyclines requiring discontinuation of anthracycline treatment were rare. A PFS of 9 months from the beginning of the coadministration of DRZ indicates that continuing anthracycline therapy beyond established cumulative doses is a promising therapeutic option.
Highlights
Anthracyclines, as the most effective therapy, are the cornerstone of advanced stage sarcoma treatment
The probability of cardiomyopathy induced by doxorubicin (DOX), the most widely used anthracycline, is clearly related to the cumulative dose
The estimated risk in adult patients increases up to 26 % at a cumulative doxorubicin dose of 550 mg/m2, which is in contrast to an estimated 7 % in an adolescent cancer patient population [8]
Summary
Anthracyclines, as the most effective therapy, are the cornerstone of advanced stage sarcoma treatment. Anthracyclines can contribute to myocardial dysfunction and congestive heart failure, limiting the therapeutic potential of the drug. Cardiotoxicity is a major concern as a late side effect of cancer treatment with anthracyclines [1]. Among several cancer therapies responsible for cardiotoxicity, anthracyclines predominantly cause myocardial dysfunction and congestive heart failure (CHF). Anthracyclines’ side effects present a great concern for sarcoma patients, since anthracyclines remain to be the most effective therapy in advanced stage sarcoma treatment [2]. More concerning are the late-onset cardiotoxic effects, most often exerted by former use of anthracycline therapy. Cardiac dysfunction is defined by left ventricular dysfunction or CHF [6]. The estimated risk in adult patients increases up to 26 % at a cumulative doxorubicin dose of 550 mg/m2, which is in contrast to an estimated 7 % in an adolescent cancer patient population [8]
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