The late consequences of anthracycline treatment on left ventricular function after treatment for childhood cancer

The purpose of this study was to determine the incidence of changes in left ventricular function in patients in long-term remission after treatment with anthracyclines for a childhood malignancy. The authors examined 155 patients in disease remission who underwent treatment protocols utilising anthracyclines in childhood. The group comprised 90 males and 65 females aged 15±4.9 years (range 5–29 years, median 15 years). The age at the time of diagnosis and start of treatment was 8.6±4.9 years (range 1–18 years, median 8 years). The time of follow-up was 7.3±4 years (range 1–21 years, median 6.3 years). The patients were given a cumulative dose of doxorubicin or daunorubicin of 250±131 mg/m² (range 50–1200 mg/m², median 240 mg/m²). The values of ejection fraction below 55% and fractional shortening below 30% assessed by means of echocardiography were considered as pathological. The control group consisted of 41 volunteers. Pathological values of fractional shortening were found in 12 patients (8%). Only one patient (0.64%) showed the development of heart failure due to cardiomyopathy. The group of the patients after chemotherapy revealed significantly worse values of left ventricular endsystolic wall stress, mean velocity of circumferential fibre shortening, Tei index, and isovolumic relaxation period in comparison with the control group. We found a correlation between the given cumulative dose of anthracyclines and indicators of systolic function of the left ventricle, but not a relation to the time indicators (age at diagnosis, time of follow-up). Conclusion:in the mean period of 6 years after chemotherapy, subclinical cardiotoxicity was found in 11 patients (7%) and cardiomyopathy with heart failure in one patient. Further indicators of subclinical damage are elevation of afterload (end-systolic stress), impaired relaxation and increased value of the Doppler index of global left ventricular function. Further monitoring and evaluation of the relevant subclinical abnormalities over a longer period of time are needed.Abbreviations CD cumulative dose - DT deceleration time - E/A index of the diastolic filling of the left ventricle - EF ejection fraction - ESS end-systolic stress - FS fractional shortening - HR heart rate - IRT isovolumic relaxation time - LV left ventricle - LVPWDd end-diastolic diameter of the left ventricular posterior wall - LVPWex excursion of the left ventricular posterior wall - LVPWP percentage of the systolic thickening of the left ventricular posterior wall - MPI myocardial performance index - mVcf _c mean velocity of circumferential fibre shortening     

High-performance liquid chromatographic bioanalysis of anthracycline cytostatic drugs

In the past decade high-performance liquid chromatography (HPLC) has developed into the most powerful tool available for the analysis of anthracycline antitumour drugs in all kinds of biological matrices. The results of drug level monitoring studies have contributed significantly to a better understanding of the pharmacokinetics and metabolic disposition of these drugs. Some aspects of anthracycline HPLC analysis in plasma samples are discussed, including the chromatographic separation and detection, sampling procedures, storage of plasma samples and sample pre-treatment.     

3D-HM监测乳腺癌患者不同化疗周期左室收缩功能变化的应用

目的探讨三维超声心动图全自动左心定量技术(3D-HM)监测乳腺癌患者不同化疗周期左室收缩功能变化的应用价值。方法收集我院以多柔比星为主进行化疗的乳腺癌患者50例,年龄29~60岁,平均(48.22±6.11)岁,于化疗前(T0)及化疗第1、2、3、4、5、6周期后(T1、T2、T3、T4、T5、T6)采用3D-HM测量左室射血分数(3D-LVEF)、左室收缩末期容积(LVESV)、左室舒张末期容积(LVEDV)。同期使用心尖双平面Simpson方法测量左室射血分数(2D-LVEF)。将所有患者化疗前后系列超声参数进行差异比较。结果(1)2D-LVEF在T6(63.08±4.63)较T0(67.20±4.22)下降,差异有统计学意义(P<0.01);LVEDd及LVESd在各化疗阶段结束后差异均无统计学意义(P>0.05);(2)3D-LVEF在T3(59.44±3.62)较T0(62.18±4.17)下降,差异有统计学意义(P<0.01),LVEDV及LVESV在各化疗阶段结束后差异均无统计学意义(P>0.05)。结论3D-HM能早期监测出乳腺癌患者化疗后左室收缩功能变化,且简便、易行,对乳腺癌患者化疗后左心功能受损的临床早期发现及干预具有一定的指导意义。     

表观遗传修饰在蒽环类药物导致心脏毒性中的作用机制研究

蒽环类药物如阿霉素(DOX)可用于多种癌症的治疗,但其引起的心脏毒性限制了其临床应用。了解阿霉素心脏毒性机制,对肿瘤心脏病学这一新兴领域的发展至关重要,如何预测、诊断和防治这种不良反应需引起高度重视和思考。由于DOX与线粒体功能障碍有关,以线粒体代谢物为底物的表观遗传修饰酶最有可能受到影响。文章对表观遗传修饰,即DNA甲基化、组蛋白修饰和非编码RNA表达进行综述,以了解DOX引起心脏毒性的表观遗传学机制。     

蒽环类耐药性乳腺癌的治疗策略

蒽环类药物是治疗乳腺癌最有效的药物之一。含蒽环类药物的联合方案（如CAF、CEF）是乳腺癌术后辅助治疗或复发转移性乳腺癌的一线方案。但曾用过蒽环类药物的乳腺癌患者,二线方案的疗效较差,治疗的难度加大,这主要是由于癌细胞对蒽环类药物产生了耐药性。     

蒽环类药物心脏毒性分析及临床使用建议

探讨蒽环类药物心脏毒性的预防、缓解措施,为其临床合理应用提供参考。方法对360 例恶性肿瘤患者使用蒽环类药物化疗后,分析其心电图及心脏保护药使用情况,比较右丙亚胺单独使用、二丁酰环磷腺苷钙针和磷酸肌酸钠合用的心脏保护疗效。结果蒽环类药物心脏毒性发生率为11.2%,结果显示,右丙亚胺单独使用、二丁酰环磷腺苷钙针和磷酸肌酸钠合用对蒽环类药物心脏毒性有保护作用,2 种心脏保护方案对蒽环类药物心脏毒性保护的疗效比较,差异无统计学意义（ >0.05）。结论蒽环类药物有致心脏毒性的作用,在化疗过程中对患者心脏功能进行监测、合理使用心脏保护药物是预防或减缓心脏毒性的有效方法。     

Anthracycline antitumour agents

A review of physicochemical and analytical properties of anthracycline antitumour agents is presented. The following subjects are discussed: protolytic equilibria, partition and partition coefficients, self-association, adsorptive properties, metal complexation, spectroscopy and chromatography. Furthermore, the stability of anthracyclines in solutions, in pharmaceutical preparations and in biological media is discussed.     

Adjuvant chemotherapy in 2005: standards and beyond

The 2003 St. Gallen consensus panel divided the many available adjuvant chemotherapy (CT) regimens into those with "standard efficacy" (ACx4, CMFx6) and those with "superior efficacy" (FA(E)Cx6, CA(E)Fx6, A(E)-->CMF, TACx6, ACx4--> paclitaxel (P)x4 or docetaxel (D)x4) but also greater complexity, toxicity and cost. This paper will summarize the latest information on long-term side effects of the "superior" regimens and 5-year benefits reported in taxane trials, including those of a "new" sequential regimen, FECx3--> docetaxelx3. Rapidly expanding evidence of marked heterogeneity in the magnitude of CT benefits according to the tumour oestrogen receptor (ER) status, a claim made for many years by IBCSG investigators, will be reviewed; it will lead to the conclusion that a revolution needs to take place in the way oncologists think about the CT added value and design adjuvant clinical trials. The conclusions proposed to the 2005 St. Gallen consensus panel are that: adequately dosed anthracycline-based CT regimens remain an acceptable standard for many women; a lower threshold for using taxanes in sequence or combination with anthracyclines (A) is justified in the presence of an ER-negative or low-ER tumour status, other aggressive biologic features (such as HER-2 overexpression), fear about A-induced cardiotoxicity; no recommendation can yet be made as far as the optimal taxane-A regimen, the best taxane or the best taxane schedule.     

Prevention of chronic anthracycline cardiotoxicity in the adult Fischer 344 rat by dexrazoxane and effects on iron metabolism

Purpose: Anthracyclines, such as doxorubicin and daunorubicin, continue to be widely used in the treatment of cancer, although they share the adverse effect of chronic, cumulative dose-related cardiotoxicity. The only approved treatment in prevention of anthracycline cardiotoxicity is dexrazoxane, a putative iron chelator. Previous in vitro studies have shown that disorders of iron metabolism, including altered IRP1–IRE binding, may be an important mechanism of anthracycline cardiotoxicity. Methods: This study examined the role of IRP1–IRE binding ex vivo in a chronic model of daunorubicin cardiotoxicity in the Fischer 344 rat and whether dexrazoxane could prevent any daunorubicin-induced changes in IRP1 binding. Young adult (5–6 months) Fischer 344 rats received daunorubicin (2.5 mg/kg iv once per week for 6 weeks) with and without pretreatment with dexrazoxane (50 mg/kg ip). Other groups received saline (controls) or dexrazoxane alone. Rats were killed either 4 h or 2 weeks after the last dose of daunorubicin to assess IRP1–IRE binding. Results: Contractility (dF/dt) of atrial tissue, obtained from rats 2 weeks after the last dose of daunorubicin, was significantly reduced in daunorubicin-treated compared to control rats. Dexrazoxane pretreatment protected against the daunorubicin-induced decrease in atrial dF/dt. However, left ventricular IRP1/IRE binding was not affected by daunorubicin treatment either 4 h or 2 weeks after the last dose of daunorubicin. Conclusions: IRP1 binding may not be altered in the rat model of chronic anthracycline cardiotoxicity.The authors state there are no conflicts of interest regarding the work in this paper.