Quintana Raymundo A, Banchs Jose, Gupta Ridhi, Lin Heather Y, Raj Sean D, Conley Anthony, Ravi Vinod, Araujo Dejka, Benjamin Robert S, Patel Shreyaskumar, Vadhan-Raj Saroj, Somaiah Neeta
Department of Cardiology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1451, Houston, TX 77030, USA.
Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Sarcoma. 2017;2017:7495914. doi: 10.1155/2017/7495914. Epub 2017 Sep 26.
Despite the dose-dependent response rate of sarcomas to doxorubicin, clinicians limit its cumulative dose due to cardiotoxicity. This study evaluates early evidence of cardiotoxicity in patients treated with high-dose doxorubicin given as a continuous infusion.
Data was collected on patients who received 90 mg/m doxorubicin as a continuous infusion and 10 gm/m ifosfamide for up to 6 cycles as part of a phase II study. Cardiotoxicity was assessed with serial echocardiograms or multigated acquisition scans and serum brain natriuretic peptide and troponin levels. Tumor responses were determined by serial radiographic imaging per RECIST.
Out of the 48 patients enrolled, no patient developed heart failure symptoms; however, 4 out of the 38 (10%) patients with serial left ventricular ejection fraction assessments developed subclinical cardiotoxicity (asymptomatic drop in LVEF ≥ 10%). Twenty-three patients received all six 72-hour cycles of doxorubicin with a mean cumulative dose of 540 mg/m. Among these patients, 4% ( = 1) developed subclinical cardiotoxicity. In the advanced disease group ( = 39), patients with a complete or partial response received a higher mean cumulative dose than those with stable disease ( < 0.033).
Doxorubicin cardiotoxicity can be limited by administering doxorubicin as a continuous infusion, allowing higher cumulative dosing to maximize efficacy.
尽管肉瘤对阿霉素的反应率呈剂量依赖性，但由于心脏毒性，临床医生会限制其累积剂量。本研究评估了接受大剂量阿霉素持续输注治疗的患者心脏毒性的早期证据。
收集了作为II期研究一部分接受90mg/m阿霉素持续输注和10gm/m异环磷酰胺治疗长达6个周期的患者的数据。通过系列超声心动图或多门控采集扫描以及血清脑钠肽和肌钙蛋白水平评估心脏毒性。根据RECIST通过系列影像学检查确定肿瘤反应。
在入组的48例患者中，没有患者出现心力衰竭症状；然而，在38例（10%）接受系列左心室射血分数评估的患者中，有4例出现亚临床心脏毒性（左心室射血分数无症状下降≥10%）。23例患者接受了全部六个72小时周期的阿霉素治疗，平均累积剂量为540mg/m。在这些患者中，4%（=1）出现亚临床心脏毒性。在晚期疾病组（=39）中，完全或部分缓解的患者比疾病稳定的患者接受的平均累积剂量更高（<0.033）。
通过持续输注阿霉素可以限制阿霉素的心脏毒性，允许更高的累积剂量以最大化疗效。
