右丙亚胺对蒽环类抗肿瘤抗生素心脏保护作用的研究进展

自二十世纪60年代阿霉素（Doxorubicin,又名Adriamycin,ADM）、柔红霉素（Daunoribicin,又名Daunomycin，DNR）、阿克拉霉素（AclacinomycinA,ACM）等蒽环类抗肿瘤抗生素相继问世以来,因其抗瘤谱广、抗瘤活性强,成为在肿瘤化疗中获得很高评价的一类药物。然而,该类药物除具有骨髓抑制、胃肠道反应、脱发等毒性外,长期使用还可发生剂量依赖性的心脏毒副作用。病理表现轻者为心电图异常、心律失常、心肌受损,重者可出现充血性心力衰竭而导致死亡[1]。临床研究表明,柔红霉素心脏毒性发生率为4％～12％,阿克拉霉素为6％～17％,阿霉素更高,当其累积剂量超过600mg/m2时，心脏毒性发生率为41％[2～4]。由于此类药物心脏毒性发生率与累积剂量明显相关,因而成为提高疗效的主要障碍。临床研究结果表明,在VitC、VitE、右丙亚胺、谷胱甘肽以及某些酚类化合物中,在减轻蒽环类抗肿瘤抗生素所致心脏毒性方面，右丙亚胺是最有前途的药物之一[5]。     

右丙亚胺对联用吡柔比星化疗患者的心脏保护作用

目的：探讨右丙亚胺对行吡柔比星化疗乳腺癌患者的心脏保护作用。方法选择行吡柔比星药物化疗的乳腺癌患者80例,随机分为两组,各40例,其中观察组接受TAC（多西他赛＋吡柔比星＋环磷酰胺）方案加右丙亚胺静脉滴注,右丙亚胺的配制浓度为吡柔比星的10倍;对照组常规接受TAC方案加安慰剂治疗。分析并比较两组患者间不同治疗阶段的心电图、左室射血分数及不良反应。结果两组患者心电图异常差异、左室射血分数从第4周开始均有统计学意义（P＜0．05）;观察组在治疗前及治疗后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吡柔比星药物化疗的乳腺癌患者的心脏耐受性,减少不良反应。     

右丙亚胺对乳腺癌患者术后化疗所致心脏毒性的保护作用

目的探讨右丙亚胺对乳腺癌患者术后行吡柔比星化疗导致心脏毒性的保护作用。方法选取2012年1月至2015年12月间在北京市石景山医院接受乳腺癌根治术及术后吡柔比星化疗的156例患者。采用随机数表法将患者分成观察组和对照组,每组78例,观察组患者术后采用在吡柔比星、环磷酰胺和紫杉醇化疗方案(AC-T化疗)基础上给予右丙亚胺治疗,对照组患者术后采用AC-T化疗方案,随访12个月,对比两组患者治疗前后左室射血分数(LVEF)、超敏肌钙蛋白T(hs-cTnT)及脑钠肽(BNP)水平,记录两组患者心电图改变以及治疗后的不良反应。结果观察组患者治疗前后的LVEF、hs-cTnT及BNP水平比较,差异无统计学意义(P>0.05),治疗3个月、6个月及12个月后,观察组患者的LVEF水平均明显高于对照组患者,差异有统计学意义(P<0.05),观察组患者治疗12个月后hs-cTnT及BNP水平均明显低于对照组患者,差异有统计学意义(P<0.05)。观察组患者治疗后的心电图改变总异常率是11.5%,明显低于对照组患者的24.4%,差异有统计学意义(P<0.05)。观察组患者治疗后的不良反应总发生率是10.3%,明显低于对照组患者的25.6%,差异有统计学意义(P<0.05)。结论右丙亚胺对乳腺癌患者术后使用吡柔比星化疗导致的心脏毒性有较好的保护作用,且用药安全性较高,值得临床推广。     

右丙亚胺治疗蒽环类药物外渗2例疗效观察

蒽环类药物（Anthracyclines）由于其抗肿瘤谱广,疗效好,是乳腺癌、白血病、淋巴瘤、子宫癌、卵巢癌等多种恶性肿瘤的一线或基本用药,而乳腺癌大多数方案均以蒽环类药物为基础。既往化疗均为外周静脉化疗,而经外周静脉置入中心静脉导管术（ peripherally inserted central venous catheters, PICC）的开展,将很多患者从外周静脉化疗的痛苦中解脱出来,但仍然有部分病人因为经济原因、PICC 穿刺禁忌或维护不便等原因,选择外周静脉化疗。而蒽环类药物外渗一直是令医护人员倍感棘手的问题,目前还没有有效的方法解救其可能造成的毁灭性后果。欧盟及美国 FDA 分别于2006年和2007年批准右丙亚胺用于治疗葸环类药物外渗的适应症［1,2］,而国内仅见1例报道［3］。我科使用右丙亚胺治疗2例蒽环类药物外渗患者,对其疗效及安全性进行观察,报道如下。     

右丙亚胺对接受表柔比星化疗的胃癌患者的心脏保护作用

目的 观察右丙亚胺对接受表柔比星(EPI)联合化疗方案的胃癌患者的心脏保护作用.方法 将66例应用含表柔比星方案化疗的患者分成右丙亚胺联合EOX化疗组和EOX化疗组2组,分别采用EOX方案化疗6个周期,以及EOX联合右丙亚胺治疗6个周期,观察2组的心电图变化,并进行比较.结果 在心电图异常发生率方面,右丙亚胺联合EOX化疗组和EOX化疗组分别为12.1%(4/33)和36.4%(12/33),2组差异有统计学意义(P<0.05).EOX化疗组中,出现心电图异常的患者中有12例予以右丙亚胺治疗,经治疗,6例出现心脏损害加重,4例异常心电图保持稳定,2例心电图恢复正常.结论 右丙亚胺对使用表柔比星的胃癌患者的心脏有一定的保护作用,并且对已经形成的损害有一定的治疗作用.     

右丙亚胺在老年乳腺癌辅助化疗中对心脏的保护作用

目的：观察右丙亚胺（dexrazoxane,DZR）对老年乳腺癌患者术后吡柔比星（pirarubicin,THP）辅助化疗时的心脏保护作用。方法：将我院乳腺中心和青岛市肿瘤医院肿瘤科治疗的120例应用 CTF（CTX ＋THP＋5－FU）方案化疗的老年乳腺癌患者随机分为观察组和对照组：对照组（不加用 DZR）和观察组（加用 DZR）（DZR∶THP ＝10∶1,即右丙亚胺和吡柔比星的用药剂量比为10∶1）。观察及统计治疗前、治疗第1个周期、第3个周期、治疗第6个周期、治疗完成后半年、治疗完成后1年的心脏事件（心前区疼痛、心率失常、心电图改变、心肌钙蛋白、B 型钠尿肽和左心室射血分数改变、充血性心功能衰竭）发生率,同时观察治疗的非心脏毒性。结果：两组患者在年龄、体重、ECOG 评分和分期方面没有统计学差异（P ＞0．05）。对照组自第1个周期开始心脏事件发生率明显上升,到治疗结束时达到最高,直到治疗后1年仍然维持在较高水平。观察组在治疗期间及治疗后心脏事件发生率较低,两组统计学差异显著（P ＜0．01）。两组的非心脏毒副反应没有明显差异。结论：THP 从第1次应用时对心脏就产生了明显的毒性,加用 DZR 可以降低这种心脏毒性,且毒副反应不明显。     

右丙亚胺成功治疗蒽环类药物外渗的临床研究

背景与目的:化疗过程中蒽环类药物的意外外渗是蒽环类药物的严重并发症,可导致组织严重创伤.以往,蒽环类药物外渗所致的较大创伤需要外科清创术和(或)皮肤移植而没有其他更好的治疗方法.近年来,临床前和临床资料显示右丙亚胺对于蒽环类药物导致的皮下损伤高度有效.本研究旨在观察右丙亚胺治疗蒽环类药物外渗的有效性和安全性.方法:80岁女性非何杰金淋巴瘤患者1例,蒽环类药物外渗后左手背红肿、溃破、剧烈疼痛,给予右丙亚胺静脉注射治疗(1 000 mg/m2,第1～2天,500 mg/m2,第3天).其有效性评定由彩色摄影和临床随访(1个月)评定.结果:患者应用右丙亚胺后,创面恢复迅速,治疗后第19天创面完全愈合,后遗症为局部轻微疼痛和色素沉着,手部功能无影响.但右丙亚胺可以增加化疗药物的骨髓抑制作用,对症处理后能缓解,未观察到其他不良反应.结论:尽管右丙亚胺治疗蒽环类药物外渗尚处于试验阶段,但其疗效令人鼓舞.本例临床研究表明该方法是有效的、安全的.     

右丙亚胺对女性乳腺癌患者术后化疗的心脏保护作用

[目的]观察右丙亚胺（DEX）对高复发风险早中期女性乳腺癌患者术后辅助化疗时的心脏保护作用。[方法]将患者随机分为治疗组和对照组,两组患者均采用EPI＋DTX为主的术后辅助化疗方案,治疗组同时加用DEX（DEX：EPI=10：1）,应用心肌肌钙蛋白T（cTnt）和左心室射血分数（LVEF）监测治疗前、第1周期、第3周期、治疗完成时、完成后半年、1年和2年的心脏功能状态,同时观察治疗的非心脏毒性。[结果]治疗组从第一周期开始cTnt明显上升,到治疗结束时达到最高,直到治疗后2年仍然维持在较高水平,而加用DEX组在治疗期间及治疗后水平都较低,两组LVEF在治疗各阶段无统计学差异．两组的非心脏副反应没有差异。[结论]EPI从第一次应用时对心脏就产生了明显的毒性,加用DEX可以降低这种心脏毒性。DEX＋EPI＋DTX方案适合具有高复发风险的女性乳腺癌的术后辅助化疗。     

右丙亚胺对于表阿霉素心脏毒性的保护作用

目的:观察右丙亚胺（dexrazoxane,DEX）对表阿霉素（EPI）辅助化疗时的心脏保护作用。方法:随机将来我院治疗的女性乳腺癌患者分为观察组和对照组,两组患者均采用EPI为主的术后辅助化疗方案,观察组在EPI为主的化疗方案基础上加用DEX（DEX∶EPI＝10∶1）,在第1次应用EPI时即给予DEX。采用心肌钙蛋白T（cTnt)和左心室射血分数（LVEF）监测治疗前、治疗第1和第3个周期、治疗完成时、完成后半年、1年的心脏功能状态,同时观察治疗的非心脏毒性。结果:两组患者在年龄、体重、ECOG评分和分期方面没有统计学差异（P>0.05）。EPI治疗第1个周期开始cTnt明显上升,到治疗结束时达到最高,直到治疗后1年仍然维持在较高水平;加用DEX组在治疗期间及治疗后cTnt水平都较低;而LVEF在两组的各个治疗阶段水平都没有统计学差异（P>0.05）;两组的非心脏不良反应没有差异。结论:EPI从第1次应用时对心脏就产生了明显的毒性,加用DEX可以降低这种心脏毒性。     

稳心颗粒配合右丙亚胺防治表柔比星心脏毒性的临床观察

目的:探讨稳心颗粒配合右丙亚胺对表柔比星所致心脏毒性的防治作用。方法:观察116例应用含表柔比星方案化疗的患者,以心电图的变化作为观察指标。先单独化疗4个周期,然后将已出现心电图异常者归入稳心颗粒配合右丙亚胺化疗组,心电图正常者分为单独化疗组与稳心颗粒配合右丙亚胺联合化疗组继续化疗2个周期,观察心电图变化。结果:单独化疗4个周期过程中,心电图异常发生率分别为24.1%(28/116)。继续化疗2个周期,单独化疗组心电图异常发生率分别为40.4%(21/52),稳心颗粒配合右丙亚胺化疗组心电图异常发生率为19.2%(10/52),(P<0.05),差异有统计学意义;稳心颗粒配合右丙亚胺治疗组有17.9%(5/28)患者异常心电图转为正常,有28.6%(8/28)患者异常心电图保持稳定,其余53.6%患者心脏损害加重。结论:稳心颗粒配合右丙亚胺对表柔比星所致心脏毒性的发生有一定的防治作用,使更多病人延长表阿霉素的治疗,并且对已经形成的心脏损害有一定的修复作用。     

Granulocytic sarcoma of the heart: extramedullary relapse of acute myeloblastic leukemia after allogeneic stem cell transplantation successfully treated by chemotherapy alone

We present a case of granulocytic sarcoma (GS) of the heart. A 28-year-old man with relapsed acute myelogenous leukemia (AML-M2) had undergone a non-myeloablative allogeneic peripheral stem cell transplantation. Three years following transplantation, masses were evidenced in his heart by echocardiography but had completely disappeared following a common chemotherapy etoposide, mitoxantrone, ara-C (EMA) regimen for relapsed AML. The involvement of the heart with GS is very rare and this is the first case of extramedullary disease in the heart after allogeneic transplantation. Here we present the case history and related literature has been reviewed.     

Clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review

This review systematically assessed the evidence on the clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer. We searched eight electronic databases, including Medline and the Cochrane Library, from inception to January 2006 for systematic reviews and randomised controlled trials that reported death, heart failure, arrhythmias or measures of cardiac performance associated with cardioprotective technologies compared with standard treatment in children treated for cancer with anthracyclines. Economic evaluations were also sought. Inclusion criteria, data extraction and quality assessment were undertaken by standard methodology. Four randomised controlled trials met the inclusion criteria of the review; each had methodological limitations. No economic evaluations were identified. Studies were combined through narrative synthesis. One trial found that continuous infusion of doxorubicin did not offer any cardioprotection over rapid infusion. One suggested that continuous infusion of daunorubicin provoked less cardiotoxicity than rapid infusion. One concluded that dexrazoxane reduces cardiac injury during doxorubicin therapy and one reported a protective effect of coenzyme Q(10) on cardiac function during anthracycline therapy. The evidence on the effectiveness of cardioprotective technologies in children is limited in quality and quantity thus making conclusions difficult. This is surprising given the importance of anthracycline use in children with cancer. Further long-term research, which includes relevant outcome measures, is needed to determine whether technologies influence the development of cardiac damage without limiting the antitumour efficacy of anthracyclines.     

Follicular dendritic cell sarcoma treated with a variety of chemotherapy

Follicular dendritic cell sarcoma (FDCS) is a very rare malignant tumor derived from follicular dendritic cells. Radical resection is the standard therapy for patients with local disease, but an optimal chemotherapy regimen has not been determined for unresectable disease. We report our experience of an FDCS patient with multiorgan involvement. In the present case, disease was only located in the pancreas initially and radical resection was performed. Multiple metastasis developed after the treatment and several factors that indicated a poor prognosis were observed. The present case had a very poor prognostic disease but survived for a long time with a good performance status because of the multiple chemotherapy regimens, which follow therapeutic strategies for malignant lymphoma and soft tissue sarcoma. As far as we know, this is the first study reporting the indication of bendamustine for FDCS patients.     

Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.     

Advanced diffuse large-cell lymphoma treated with 12-week combination chemotherapy: Natural history of relapse after initial complete response and prognostic variables defining outcome after relapse

Purpose: To define both the natural history of and prognostic factors affecting outcome post relapse from a complete response in advanced stage diffuse large-cell lymphoma.Patients and methods: A total of 468 patients aged 17–74 years received the 12-week duration chemotherapy regimens MACOP-B, VACOP-B and ACOP-12 between 1 April 1981 and 31 December 1995 for advanced stage diffuse large, mixed or immunoblastic lymphoma. Of these 402 entered a complete remission, 97 (24%) of whom subsequently relapsed. Initial staging data, follow-up, and relapse information were analyzed to define the natural history of relapse and also subjected to univariate and multivariate correlation with overall (OS) and failure free survival (FFS).Results: Eleven percent of the relapses were low grade. All other relapses were of intermediate grade with 75% occurring within the first two years, the remainder up until the eleventh year. Median and five-year OS from the time of relapse for intermediate grade relapse were 12 months and 20%; for FFS they were eight months and 18% respectively. Adverse independent factors, for both OS and FFS were: less than one year to relapse, decreasing performance status at relapse, and more than three nodal sites at relapse.Conclusions: Low-grade relapse is not uncommon in patients who initially presented with diffuse large cell lymphoma. As the management of low- and intermediate grade disease is so different biopsy proof of the nature of the relapse is of value. The prognostic factors identified need to be taken into consideration when analyzing results from trials of secondary treatment so as to avoid erroneous conclusions about comparative treatment efficacy.     

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

Little literature exists on the safety of early pregnancy following chemotherapy. Here we assess the rate of relapse and foetal outcome in women who have completed single and multi-agent chemotherapy for gestational trophoblastic tumours. The records of 1532 patients treated for persistent gestational trophoblastic tumours at Charing Cross Hospital between 1969 and 1998 were reviewed. Patients were defined as receiving single agent or multi-agent treatment. Relapse rates and foetal outcome were reviewed in the 230 patients who became pregnant within 12 months of completing chemotherapy. In the single agent group 153 (22%) of 691 patients conceived early. Three subsequently relapsed. In the multi-agent group, 77 (10%) of 779 patients conceived early, two then relapsed. Relapse rates were 2% (3 out of 153) and 2.5% (2 out of 77) for each group compared to 5% and 5.6% in the comparative non-pregnant groups. Outcomes of 230 early pregnancies: 164 (71%) delivered at full term, 35 (15%) terminations, 26 (11%) spontaneous abortions, three (1.3%) new hydatidiform moles and two (1%) stillbirths. Early pregnancies were more common in the single agent group (P<0.001), but spontaneous miscarriages and terminations were more likely to occur in the multi-agent group (P=0.04 and 0.03, respectively). Of the full-term pregnancies, three (1.8%) babies were born with congenital abnormalities. Patients in either group who conceive within 12 months of completing chemotherapy are not at increased risk of relapse. Though, we still advise avoiding pregnancy within 12 months of completing chemotherapy, those that do conceive can be reassured of a likely favourable outcome. DOI: 10.1038/sj/bjc/6600041 www.bjcancer.comCopyright 2002 The Cancer Research Campaign     

右丙亚胺对表柔比星所致心脏毒性防治作用的观察

目的:观察右丙亚胺对表柔比星所致心脏毒性的防治作用。方法:对84例应用含表柔比星方案化疗的患者,以心电图作为观察指标,先单独化疗4个周期,然后将已出现心电图异常者归入右丙亚胺治疗组、心电图正常者分为单独化疗组及右丙亚胺联合化疗组继续单独化疗或用右丙亚胺联合化疗2个周期,观察心电图变化。结果:单独化疗4个周期过程中,心电图异常发生率为26.2%(22/84)。继续化疗2个周期,单独化疗组心电图异常发生率为38.7%(12/31),右丙亚胺联合化疗组心电图异常发生率为16.1%(5/31),RIDIT公式统计,u=1.977,P<0.05,差异有统计学意义;右丙亚胺治疗组有13.6%(3/22)患者异常心电图转为正常,有18.2%(4/22)患者异常心电图保持稳定,其余68.2%患者心脏损害加重。结论:右丙亚胺对表柔比星所致心脏毒性的发生有一定的防护作用,并且对已经形成的损害有一定的治疗作用。