Efficacy and safety of Dexrazoxane (DRZ) in sarcoma patients receiving high cumulative doses of anthracycline therapy – a retrospective study including 32 patients

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.

Low dose radiation prevents doxorubicin-induced cardiotoxicity

“…Studies with animal models of cardiac overexpression of certain antioxidants such as catalase and metallothionein have shown the well protection from DOX-induced cardiotoxicity [ 7 , 8 ]. To date, despite Dexrazoxane, an intracellular iron chelator to reduce the potential generation of iron-derived free radicals, has been approved as a prophylactic medication used in clinical practice for the cancer patients who received DOX treatment [ 10 ], the potentially hematological toxicities of Dexrazoxane promotes remains to further search for a better approach that can ameliorate DOX cardiotoxicity without compromising its antineoplastic activity [ 10 ]. Current two major concerns include: (a) Exogenous administration of antioxidants could not maintain consistent levels between two dosing [ 10 – 13 ]; therefore, it may be a better way to induce endogenous cardiac antioxidants; (b) Systemic administration of any drug may not only protect against DOX cardiac toxicity, but also reduce the efficacy of DOX cancer therapy [ 10 – 13 ]; therefore, any non-invasive approach that can specifically stimulate cardiac antioxidant capacity may be a better strategy to prevent DOX cardiac toxicity without impact on its cancer therapeutic effects.…”

Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series

“…Dexrazoxane has also been shown to be cardioprotective in elderly patients with acute myeloid leukemia or small cell lung cancer [36,37]. Similarly, dexrazoxane provided marked cardioprotection against epirubicin-related cardiotoxicity in patients with breast cancer or sarcoma with no evidence of reduced antitumor activity [38,39].…”

Systemische Therapieoptionen bei lokal fortgeschrittenen und metastasierten myxoiden, dedifferenzierten und pleomorphen Liposarkomen

“…In späteren Therapielinien kommen neben experimentellen Therapieansätzen im Rahmen klinischer Studien, die für geeignete Patienten bei entsprechender Verfügbarkeit immer erwogen werden sollten, auch eine Anthrazyklin-Rechallenge unter Kardioprotektion mit Dexrazoxan [53] oder eine Trabectedin-Rechallenge in Betracht. Dagegen stellen Ifosfamid (spätestens ab der 2.…”

“…Docetaxel (insbesondere für Patienten mit PLS) sowie ggf. eine Anthrazyklin-Rechallenge unter Kardioprotektion mit Dexrazoxan[53] stellen wirksame Therapieoptionen in der 2. und in späteren Therapielinien dar. Die Auswahl und ggf.…”