右丙亚胺对行蒽环类药物化疗乳腺癌患者的心脏保护作用

目的探讨右丙亚胺对行蒽环类药物化疗乳腺癌患者的心脏保护作用。方法选择行蒽环类药物化疗的乳腺癌患者90例,随机分为两组,各45例,其中对照组使用阿霉素进行术后辅助化疗,观察组在对照组的基础上加用右丙亚胺静脉滴注,维持30min,并右丙亚胺的配置浓度为阿霉素的10倍,比较两组患者不同治疗阶段左室射血分数及不良反应。结果自治疗4周开始,对照组左室射血分数显著低于观察组（P〈0．05）,观察组治疗前及治疗后1年随访期间,左室射血分数差异无统计学意义（P〉0．05）,观察组治疗期间消化道反应、脱发及恶心呕吐的发生率均明显低于对照组（P〈0．05）。结论右丙亚胺能提高行含蒽环类药物化疗的乳腺癌患者的心脏耐受性,减少不良反应。     

Recent advances in medical management of hepatocellular carcinoma

Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during the last decade. A fine powder formulation of cisplatin and the new platinum agent miriplatin became standard medicines in addition to anthracyclines in transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon‐occluded TACE is an effective therapy for localized HCC and drug‐eluting microspheres seemed to show a higher response rate in certain HCCs, the definite advantages of those procedures still remain uncertain. Intermediate stage HCC, or Barcelona Clinic Liver Cancer stage B, is regarded as a heterogeneous category with a wide spectrum of tumors and patients, and several subclassifications of the stage have been proposed to show different prognoses; there are also different recommended therapies in each subgroup. Authors have subclassified patients based on combinations of tumor size, tumor number, and liver function, with or without performance status. Because of differences of available medical resources and techniques in treatment procedures between countries, the most ideal and useful subgrouping remains inconclusive at present. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second‐line therapy. Other molecular‐targeted and immune‐oncological medicines are expected to follow in the near future. Some studies have suggested an advantage of early introduction of molecular‐targeted therapy for TACE‐resistant HCC in the intermediate stage.     

一例蒽环类药物心脏毒性的用药分析

蒽环类药物的剂量限制性心脏毒性限制了其在临床上的应用。本文就一例恶性淋巴瘤患者用药后出现的心脏毒性反应,对蒽环类药物心脏毒性的发生机制、危险因素、监测和防治等方面作一综述。     

血清N末端脑钠肽前体早期诊断蒽环类药物心脏毒性的实验研究

目的:探讨血清N末端脑钠肽前体(NT-proBNP)浓度是否可成为蒽环类药物心脏毒性的早期诊断指标.方法:新西兰雄性兔44只随机分为对照组和实验组,对照组新西兰兔静脉注射等体积的生理盐水,实验组分为4组,每次给予阿霉素2 mg/kg,每周1次,根据给药周数不同,分为1周组、2周组、4周组和8周组.经胸超声心动图测量左室射血分数(LVEF)和左室短轴缩短分数(FS)以及E峰和A峰比率,血清NT-proBNP浓度测量采用酶联免疫吸附测定法(ELISA),心肌光镜Billingham评分和电镜检查评价蒽环类药物心脏毒性.结果:8周组新西兰兔LVEF、FS以及E/A比率均下降(P<0.05),4周组新西兰兔心肌病评分高于对照组、1周组和2周组(P<0.05).八周组新西兰兔心肌病评分高于其余各组新西兰兔(P<0.05).心肌电镜检查结果证实二周组、四周组和八周组新西兰兔心肌损伤.与对照组血清NT-proBNP浓度相比,二周组、四周组和八周组新西兰兔血清NT-proBNP浓度均明显上升(P<0.05).通过相关分析提示血清NT-proBNP浓度与阿霉素累积剂量及心肌损害的程度呈正相关.结论:血清NT-proBNP浓度可能是蒽环类药物心脏毒性较早期诊断指标.     

The predictive and prognostic significance of pre- and post-treatment topoisomerase IIα in anthracycline-based neoadjuvant chemotherapy for local advanced breast cancer

Objective

To investigate the predictive and prognostic value of topoisomerase IIα (Topo IIα, Topo II) expression in the primary tumors and residual tumors of local advanced breast cancer (LABC) patients being treated with anthracycline-based neoadjuvant chemotherapy (NCT).

Methods

The data from 283 LABC patients who had been treated with anthracycline-based neoadjuvant chemotherapy were collected. The expression of Topo IIα, HER-2 and other biomarkers was determined via immunohistochemical analysis in pre- and post-chemotherapy specimens. The status of pre-treatment biomarkers was correlated with the clinical response determined by the RECIST 1.1 criteria, whereas the post-treatment biomarkers were studied for prognostic value using the Cox model.

Results

By analyzing the complete data from 99 patients, the co-expression of HER-2/Topo IIα was found to be significantly correlated with the clinical response to chemotherapy (Logistic regression P = 0.042). Notably, a 20% alteration in the Topo IIα status during neoadjuvant chemotherapy was found, which could also influence the sensitivity to treatment. With a survival analysis performed in 245 patients with residual tumors after NCT, node metastasis, HER-2 and Ki-67 were independent predictors of patient outcome. However, post-treatment Topo IIα expression demonstrated significant prognostic value in HER-2+ patients (P = 0.002). A relatively lower disease-free survival and overall survival was observed in HER-2+/Topo- patients (log rank P = 0.010 for DFS and P < 0.001 for OS).

Conclusion

Topo IIα, together with HER-2, might help to select for patients who could benefit from anthracycline-based neoadjuvant chemotherapy and identify non-complete responders at a higher risk of disease recurrence or death.     

A LONGITUDINAL STUDY OF CARDIAC FUNCTION IN CHILDREN WITH CANCER OVER 40 MONTHS

A previous study demonstrated impaired systolic function in 29% of patients treated with an thracycline as part of their therapy for malignant disease. A follow-up echocardiographic study was performed to determine whether there had been further deterioration of cardiac function. At least 40 months after the first study, those patients in whom abnormal systolic function had been detected and who had not received further anthracycline were studied by echocardiography using the same protocol as the initial study (group A). A second group of pediatric oncology patients who had not been given anthracycline but who had previously had cardiac assessment was selected as a control group (group N). The age and sex distributions of the two groups were comparable. Group A comprised 29 patients assessed on 2 occasions at mean times of 46 months and 89 months from the last dose of anthracycline. The mean dose of anthracycline received was 233 mg/m² (range 20-400). Nine of 16 patients and 4 of 5 patients who had abnormal ejection fraction (EF) and fractional shortening (FS) at first assessment had normal EF and FS at the second assessment. There were no significant changes in EF, FS, and left ventricular wall stress (LVWS) between the two examinations. In group N, 20 patients were assessed after a mean interval of 43 months. There were no significant changes in EF, FS, or LVWS between the two examinations. At the first but not the second examination there were significant differences in the left ventricular internal diameters, EF, FS, and LVWS between group A and group N. Mildly abnormal cardiac indices detected in children after cessation of treatment with anthracycline did not deteriorate in 3 to 4 years follow-up. A longer cardiac follow-up study is indicated to assess the late outcome.     

紫杉类药物用于可手术乳腺癌的辅助化疗

目的:蒽环类药物化疗方案中加入紫杉类药物能否提高可手术乳腺癌患者的生存获益.方法:选择2006年1月至2009年1月的初治乳腺癌患者391例,分为不含紫杉类药物组(CEF组138例,CTF组97例),含紫杉类药物组(TEC组98例,TTC组58例).以无病生存作为第一观察终点,以死亡作为第二观察终点.结果:中位随访47个月,不含紫杉类药物组患者中无病生存(DFS)占90.1％,总生存(0S)为97.7％,含紫杉类药物化疗组患者中DFS为90.0％,OS为97.6％,均无明显统计学意义.含紫杉类药物组有较高的Ⅲ度以上白细胞下降率和心脏损害发生率(P＜0.01).结论:蒽环类方案中加入紫杉类药物未显著改善患者DFS和OS.     

蒽环类药物及蒽环序贯紫杉类方案对乳腺癌辅助化疗后心脏毒性的影响

目的 研究蒽环类药物及蒽环序贯紫杉类两种化疗方案,对乳腺癌辅助化疗后引起的心脏毒性影响.方法 乳腺癌辅助化疗患者84例,根据化疗方案的不同,将其分为蒽环类组42例和蒽环序贯紫杉类组42例.蒽环类组患者接受蒽环类药物化疗方案治疗,而蒽环序贯紫杉类组则接受蒽环序贯紫杉类化疗方案治疗.试验过程中,分别于化疗前、首次化疗后及末次化疗次日3个实验时间点上,测定所有研究对象的静脉肌钙蛋白T和肌红蛋白含量,同时借助自制心脏毒性评级表评价患者心脏毒性级别,以评估上述两种化疗方案对患者引起的心脏毒性程度.结果 两种化疗方案组患者在进行辅助化疗后,静脉肌钙蛋白T含量均没有超出正常范围(P<0.1 ng/ml);在末次治疗后,蒽环序贯紫杉类组静脉肌钙蛋白T含量为(0.0210±0.0166)ng/ml,而另外一组为(0.0390±0.0168)ng/ml,前者低于后者,但无统计学意义(P>0.05);两组患者在3个实验时间点上的肌红蛋白含量均未发生明显变化,且均低于21 ng/ml;两组患者末次化疗后心脏毒性评级表情况,未出现明显差异.结论 蒽环序贯紫杉类化疗方案较蒽环类药物化疗方案,并没有引起患者心脏毒性的明显增大;静脉肌钙蛋白T含量及肌红蛋白含量在评估患者心脏毒性程度方面发挥一定的作用,但尚存在进一步优化之处.