Schuler Markus K, Gerdes Sebastian, West Antje, Richter Stephan, Busemann Christoph, Hentschel Leopold, Lenz Felicitas, Kopp Hans-Georg, Ehninger Gerhard, Reichardt Peter, Pink Daniel
Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Department of Internal Medicine II, HELIOS Clinic Emil von Behring, Walterhöferstr. 11, 14165, Berlin, Germany.
BMC Cancer. 2016 Aug 9;16:619. doi: 10.1186/s12885-016-2654-x.
Anthracyclines, 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.
The 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.
The median age was 54 years [18-68 years]. The median cumulative anthracycline dose before adding DRZ was 450 mg/m(2) and after administration of last anthracycline containing therapy 750 mg/m(2). 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.
Chemotherapy 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.
蒽环类药物作为最有效的治疗方法，是晚期肉瘤治疗的基石。然而，蒽环类药物也会导致心肌功能障碍和充血性心力衰竭，最终限制了该药物的治疗潜力。已证明联合使用右丙亚胺可有效降低心脏毒性，但主要是在患有肉瘤以外疾病的患者中。
这项回顾性分析的目的是评估高累积剂量蒽环类药物联合右丙亚胺化疗的安全性和有效性。分析了在四个机构接受治疗的32例患者的病历。联合用药的原因是再次挑战、达到蒽环类药物累积剂量以及既往存在心力衰竭。
中位年龄为54岁[18 - 68岁]。添加右丙亚胺之前蒽环类药物的中位累积剂量为450mg/m²，在最后一次含蒽环类药物治疗给药后为750mg/m²。在治疗期间或随访期间，2/27例（7%）既往无重大心脏问题的患者发生了蒽环类药物诱导的心脏毒性。从开始首次含蒽环类药物化疗起的中位总生存期（OS）为46个月，从首次联合使用右丙亚胺起为17个月。在再次挑战时，联合使用右丙亚胺的中位无进展生存期（PFS）为7个月。在持续治疗中，从化疗开始起的中位PFS为13个月，从添加右丙亚胺起为9个月。
高累积剂量蒽环类药物联合右丙亚胺化疗在这些晚期疾病患者中显示出显著的总生存期。因高累积剂量蒽环类药物导致需要停用蒽环类药物治疗的心脏副作用很少见。从联合使用右丙亚胺开始起9个月的无进展生存期表明，在既定累积剂量之外继续蒽环类药物治疗是一种有前景的治疗选择。
