二尖瓣环位移自动追踪技术评价蒽环类药物对乳腺癌病人左室收缩功能的影响

目的 应用二尖瓣环位移自动追踪技术评价蒽环类药物对乳腺癌病人左室收缩功能的影响,探讨反映左室功能受损较为准确和敏感的参数.方法 收集2018年10月至2019年12月于山西医科大学第二医院乳腺外科诊断为乳腺癌的女性病人50例,均行以表柔比星为主的化疗方案,分别于化疗前、化疗2及4周期后,行常规超声心动图、二维斑点追踪技术(2D-STI)及二尖瓣环位移自动追踪技术(TMAD)检查,获得左室射血分数(LVEF)、左室整体纵向峰值应变(LVGLS)及二尖瓣环连线中点最大位移与左心室舒张期末最大纵径比值(Mid％).比较化疗前后以上各参数的差异.结果 与化疗前比较,化疗4周期后LVEF降低,化疗前(67.85±4.16)％,化疗4周期后(63.35±4.49)％;与化疗前比较,化疗2、4周期后LVGLS降低,化疗前(?22.78±1.93)％,化疗2周期后(-18.85±1.02)％,化疗4周期后(-16.97±1.07)％;与化疗前比较,化疗2、4周期后Mid％均值降低,化疗前(17.52±0.96)mm,化疗2周期后(14.92±0.76)mm,化疗4周期后(12.99±0.98)mm;化疗前后各周期Mid％均值与LVEF呈弱相关(r=0.452,0.505,0.435,P<0.05),与LVGLS呈强相关(r=0.815,0.802,0.857,P<0.05);ROC曲线分析显示化疗4周期后LVGLS和Mid％均值预测蒽环类药物心脏毒性的ROC曲线下面积分别为0.962及0.912;重复性检验结果显示LVGLS和Mid％均值的观察者内ICC值分别为0.885、0.912,观察者间ICC值分别0.841、0.900;LVEF、LVGLS及Mid％均值与药物剂量均呈负相关(r=-0.398,-0.876,-0.906,P<0.05).结论 TMAD技术可早期识别化疗病人左心室整体收缩功能障碍,Mid％均值较LVGLS测量简便易行且重复性好,可作为敏感参数.     

Health‐Related Quality of Life With Adjuvant Docetaxel‐ and Trastuzumab‐Based Regimens in Patients with Node‐Positive and High‐Risk Node‐Negative,HER2‐Positive Early Breast Cancer: Results from the BCIRG 006 Study

Background.

This study aims to describe and compare health-related quality of life (HRQL) in patients with node-positive and high-risk node-negative HER2-positive early breast cancer receiving adjuvant docetaxel and trastuzumab-based or docetaxel-based regimens alone.

Methods.

Eligible patients (n = 3,222) were randomly assigned to either four cycles of adjuvant doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC→T) or one of two trastuzumab-containing regimens: adjuvant doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab administered for 1 year (AC→TH) or six cycles of docetaxel plus carboplatin combined with trastuzumab administered for 1 year (TCH). The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and BR-23 were administered at baseline, the start of cycle 4 (mid), and the end of chemotherapy (EOC), as well as at 6, 12, and 24 months after chemotherapy.

Results.

Compliance rates for the EORTC questionnaires were acceptable at 72%–93% of eligible patients out to the 12-month assessment. Systemic side effect (SE) change scores were significantly improved for TCH-treated patients compared with AC→TH and AC→T at EOC, suggesting improved tolerability. Physical functioning (PF) was only slightly worse at midpoint for those receiving TCH, compared with patients who were just starting on taxane in an AC→TH regimen, but was otherwise similar between arms. All treatment arms recovered from the deterioration in SE, PF, and Global Health Scale scores by 1 year and median future perspective change scores continued to improve throughout treatment and follow-up.

Conclusion.

HRQL outcomes for adjuvant docetaxel and trastuzumab-based regimens are favorable and support TCH as a more tolerable treatment option.     

蒽环类药物心脏毒性及其预防措施

蒽环类抗癌药是对多种恶性肿瘤具有高效作用的化疗药物,但由于其心脏毒性,在临床上受到使用限制。本文将就蒽环类药物心脏毒性的临床特点、发生机制、临床检测及预防措施作一综述。     

NP方案与XD方案治疗应用蒽环类药物治疗失败的乳腺癌的疗效观察

目的 观察诺维本联合顺铂(NP方案)与多西紫杉醇联合希罗达(XD方案)治疗应用蒽环类药物治疗失败的乳腺癌的疗效及不良反应.方法 将64例应用蒽环类药物治疗失败的乳腺癌患者随机分为两组,NP组34例,治疗方法:NVB25 mg/m2,静脉输注,第1、8天;DDP25 mg/m2,静脉输注,第2、3、4天.每21 d为1个治疗周期.XD组30例,治疗方法:DOC 75 mg/m2,静脉输注,第1天;XELODA 1275 mg/m2,口服,每日2次,第1～14天.两组均以21 d为1个治疗周期,每例至少完成2个周期.结果 NP方案总有效率(41.2%)与XD方案总有效率(50.0%)差异无统计学意义(P>0.05);两组不良反应均以粒细胞减少、恶心呕吐为主,经对症处理后可耐受.结论 NP方案与XD方案对治疗应用蒽环类药物治疗失败的乳腺癌患者均有较好疗效,可选择应用.     

Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer

Objectives This study evaluated the incidence of late cardiotoxicity after dose-dense and -intense adjuvant sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) for breast cancer (BC) with ≥ 4 involved ipsilateral axillary lymph nodes. Methods Patients were enrolled from 1994 to 2001 after definitive BC surgery if ≥4 axillary nodes were involved. Planned treatment was A 90 mg/m² q 14 days × 3, T 250 mg/m² q 14 days × 3, C 3 g/m² q 14 days × 3 with filgrastim (G) support. Left ventricular ejection fraction (LVEF) was monitored using equilibrium radionuclide angiography (ERNA) before the initiation of chemotherapy, and after three cycles of each chemotherapeutic agent. At a median follow-up of 7 years, we obtained ERNA scans on 32 patients to evaluate the long-term cardiotoxicity of this regimen. Results Eighty-five eligible patients enrolled on the treatment protocol. Clinical heart failure developed in one patient. Seven (8%) patients had LVEF < 50% at the end of therapy. No cardiac-related deaths occurred. Thirty-two (46%) of 69 surviving patients have consented to late cardiac imaging. At a median follow-up of 7 years, the median absolute change in LVEF from baseline was -5.5%; [range (−8%) to (+36%)], and from the end of chemotherapy was −2.0%; [range (−25%) to (+16%)]. Four patients (12%) had a LVEF < 50%; two of these four patients had an LVEF of < 50% at the end of chemotherapy. Conclusions Late development of asymptomatic decline in cardiac function may occur after dose-dense and -intense adjuvant therapy, but is uncommon.     

Subacute anthracycline cardiotoxicity

We describe the case of 25-year-old man, with acute myeloid leukaemia, who presented with a myopericarditis syndrome 17 days post consolidation chemotherapy with high dose cytarabine and idarubicin. Transthoracic echocardiography showed marked transient increased left ventricular wall thickness associated with normal systolic contraction. In conjunction, pulsed tissue Doppler analysis revealed low early diastolic annular velocities, consistent with diastolic dysfunction. Endomyocardial biopsy showed severe interstitial myocardial oedema in the absence of a cellular infiltrate or myofibre damage. We believe this is the first case of subacute anthracycline toxicity described with the pathological findings of isolated myocardial oedema.     

Intravenous and oral demethoxydaunorubicin (NSC 256–439) in the treatment of acute leukemia and lymphoma: A pilot study

Summary Demethoxydaunorubicin (DMDR), a new anthracycline available both for intravenous and oral administration, was given in 14 cases of leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) replacing either daunorubicin (DNR) or doxorubicin (DOX) in conventional chemotherapy regimes.In acute leukaemia (6 myeloblastic and 1 common lymphoblastic) there were 5 complete (CR) and 2 partial (PR) remissions; one patient, previously brought into remission with a regime including i. v. DMDR was thereafter maintained in CR with oral DMDR.Among the patients treated with the oral DMDR, 2 NHL cases were treated; 1 patient had a sustained remission of 12 months so far, with DMDR alone; another patient had a CR with a combined regime. In MM, one patient with very advanced disease treated with i. v. DMDR/CHOP did not respond, but three cases treated with oral DMDR plus other drugs showed a partial remission.Toxic effects were limited to brief episodes of nausea and vomiting in a few i. v. treated patients; a prolonged bone marrow depression was observed in one case only. No cardiotoxic effect was recorded.     

Characterisation of a Cellular Model of Cardiomyopathy, in the Rabbit, Produced by Chronic Administration of the Anthracycline, Epirubicin

The objective of this study was to assess the structural, mechanical and electrophysiological changes associated with chronic administration of epirubicin (Pharmorubicin), which is a cardiotoxic anthracycline antibiotic used in conventional cancer chemotherapy. New Zealand white rabbits (8 weeks) were treated with twice-weekly infusions of epirubicin (2 mg/kg) or saline for a period of 6 weeks, followed by a wash-out period of 2 weeks. Myocardial damage consistent with cardiomyopathy was observed in the epirubicin-treated animals; electron micrographs indicated myofibril loss together with separation of the intercalated disc and dilation of the sarcotubular system. Contractile function, as measured by mechanical shortening, action potentials and -type Ca²⁺currents were examined in ventricular cardiomyocytes, which were isolated by means of enzymatic dissociation using collagenase. There was an attenuation in the contractile response to isoprenaline in cardiomyocytes isolated from the hearts of epirubicin-treated rabbits compared to control rabbits. Cardiomyocytes isolated from epirubicin-treated rabbits had greater basal contractile amplitude (11.0±0.3 %dL,n=8) than control myocytes (8.2±0.3 %dL,n=9), but had similar maximum responses of 19.1±0.6 %dL, and 17.3±0.5 %dL, respectively, when stimulated with 1μ isoprenaline. No differences were noted in the peak -type Ca²⁺current of myocytes isolated from the hearts of control and epirubicin-treated rabbits; however, in the latter, there was a prolongation of the action potential duration (396±25 ms) compared to that in controls (321±26 ms). These results demonstrate structural and mechanical alterations in ventricular cardiomyocytes which are compatable with a mild cardiomyopathy following chronic treatment with the anthracycline, epirubicin. The increase in basal contraction is likely to be due to more efficient coupling of electrical stimulation, and the depressed inotropic responsiveness following stimulation with isoprenaline indicates that there may be changes in cell membrane properties. Compared to control cardiomyocytes, cells isolated from the hearts of epirubicin-treated rabbits were more heterogeneous, with respect to cell dimensions, and had significantly different electromechanical properties.     

Potential role of pemetrexed in metastatic breast cancer patients pre-treated with anthracycline or taxane

ObjectivesThis article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens.MethodsPubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ‘‘pemetrexed’’ or ‘‘{"type":"entrez-nucleotide","attrs":{"text":"LY231514","term_id":"1257767600","term_text":"LY231514"}}LY231514’’ or “Alimta”, “metastatic breast cancer”, and “advanced breast cancer”.ResultsThere were 15 studies (n = 1002) meeting our criteria for evaluation. Eight single-agent trials (n = 551) and seven using combinations with other agents (n = 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B₁₂, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer.ConclusionPemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists.