含脂质体阿霉素AC-T方案在乳腺癌辅助化疗中安全性临床分析

目的 观察含脂质体阿霉素AC-T方案相较EC-T方案辅助化疗治疗乳腺癌的临床用药安全性。方法 回顾性分析102例乳腺癌术后辅助化疗患者临床资料,含脂质体阿霉素组48例给予AC-T方案治疗,表柔比星组54例给予EC-T方案治疗,化疗后评估化疗不良反应及临床用药安全性。结果 含脂质体阿霉素组在化疗后骨髓抑制、肝功损伤及心脏毒性等不良反应方面优于表柔比星组,差异有统计学意义（P <0.05）;含脂质体阿霉素组在手足综合征方面发生率及严重程度明显较表柔比星组严重,差异有统计学意义（P <0.05）。而两组在胃肠道反应、过敏反应、脱发、周围神经炎等方面差异无统计学意义（P> 0.05）。结论 含脂质体阿霉素AC-T方案治疗乳腺癌较传统EC-T方案在骨髓抑制、肝功损伤及心脏毒性方面不良反应轻,临床用药安全性高,而在手足综合征方面不良反应重,应引起临床重视。     

表柔比星联用右丙亚胺和多柔比星脂质体对化疗所致心脏毒性的临床研究

目的观察表柔比星联用右丙亚胺和多柔比星脂质体对化疗所致心脏毒性的保护作用。方法将96例乳腺癌术后患者分为右丙亚胺组、多柔比星脂质体组和对照组,三组患者均接受以蒽环类药物为基础的术后辅助化疗方案4周期,通过监测各时期心电图异常率、心脏彩超左心室射血分数（LVEF）、短轴缩短率（SF）来评估心脏功能。结果对照组化疗后心电图异常率最高,右丙亚胺组、多柔比星脂质体组均能明显降低心电图异常率,且从化疗后1周期就显示出心脏保护作用;而LVEF及SF的变化在三组患者化疗前后差异无统计学意义（P〉0.05）。结论表柔比星化疗时加用DEX或者使用多柔比星脂质体对减轻蒽环类药物心脏毒性是有效且安全的。     

多柔比星脂质体与表柔比星在乳腺癌化疗中的应用效果比较

目的 比较多柔比星脂质体与表柔比星在乳腺癌化疗中的应用效果。方法 选取2018年6月—2020年6月湖南省妇幼保健院收治的乳腺癌化疗患者84例,采用随机数字表法分为观察组和对照组,各42例。对照组治疗方案为“表柔比星+环磷酰胺×4→多西他赛×4”,观察组治疗方案为“多柔比星脂质体+环磷酰胺×4→多西他赛×4”。2组同以21 d为1个疗程,持续治疗4个疗程,每2周复查1次乳腺B型超声检查。比较2组近期疗效,治疗前后肿瘤标记物[血清细胞角蛋白12-1(CYFRA12-1)、糖类抗原15-3(CA15-3)、血清癌胚抗原(CEA)]水平及不良反应。结果 观察组患者疾病控制率(DCR)为95.24%,高于对照组的80.95%(χ²=4.087,P=0.043);治疗4个疗程后,2组CYFRA21-1、CEA、CA15-3水平均较治疗前降低,且观察组低于对照组(P均<0.01); 2组患者过敏反应、心肌损害、脱发等不良反应Ⅲ～Ⅳ度发生率的比较差异均无统计学意义(P> 0.05),但观察组Ⅰ～Ⅱ度发生率均低于对照组(P <0.05)。结论 多柔比星脂质体相较...     

吡柔比星与表柔比星在乳腺癌新辅助化疗中的成本-效果分析

目的:比较吡柔比星与表柔比星在乳腺癌新辅助化疗中的成本-效果。方法:将188例乳腺癌新辅助化疗患者按治疗方案的不同分为CTF组(91例)与CEF组(97例)。CTF组术前经吡柔比星+环磷酰胺+氟尿嘧啶辅助化疗;CEF组术前经表柔比星+环磷酰胺+氟尿嘧啶辅助化疗,2组均进行4个周期。治疗后运用药物经济学原理进行成本-效果分析。结果:2组治疗总有效率为86.8%和90.7%,差异无统计学意义(P>0.05);2组均出现不同程度的不良反应,但差异无显著性(P>0.05)。CTF与CEF组的成本-效果比分别为198.59和248.73,2组比较差异有统计学意义(P<0.05)。结论:吡柔比星新辅助化疗方案治疗乳腺癌与表柔比星方案疗效相当,但更为经济。     

多西他赛、表柔比星及环磷酰胺联合化疗对乳腺癌新辅助化疗患者疗效观察

目的:探讨乳腺癌新辅助化疗患者采用多西他赛、表柔比星、环磷酰胺联合化疗的疗效。方法:72例乳腺癌新辅助化疗患者按入院先后顺序分为观察组和对照组各36例。两组均行手术治疗,并在手术前后分别进行6个周期的化疗。观察组采用多西他赛、表柔比星及环磷酰胺联合化疗;对照组采用多西他赛与表柔比星联合化疗。比较两组患者的疗效以及不良反应。结果:观察组疗效总体分布明显优于对照组(P<0.05),且显效率、总有效率均高于对照组(P<0.05)。观察组患者中性粒细胞减少发生率明显高于高于对照组(P<0.05),其他各项不良反应发生情况两组比较,差异无统计学意义(P>0.05)。结论:乳腺癌新辅助化疗患者采用多西他赛、表柔比星及环磷酰胺联合化疗,疗效明显优于多西他赛与表柔比星联合化疗,且不良反应并无显著增加,值得临床推广。     

吡柔比星、多柔比星治疗非霍奇金淋巴瘤的疗效对比观察

目的：了解吡柔比星与多柔比星用于非霍奇金淋巴瘤（NHL）化疗的临床疗效。方法：选择本科2007年7月～2010年6月收治并确诊的NHL患者85例,将其随机分为吡柔比星组48例接受以吡柔比星为主的化疗方案,多柔比星组37例接受以多柔比星为主的化疗方案,对比分析两组的疗效与不良反应。结果：吡柔比星组化疗的有效率为83.3%,多柔比星组为67.6%,两组比较,差异有统计学意义（P〈0.05）。多柔比星组发生较多的心脏毒性反应,吡柔比星组则未发生心脏毒性反应,吡柔比星对胃肠道的不良反应较低。结论：与多柔比星为主的方案相比,以吡柔比星为主的化疗方案NHL的疗效更佳,不良反应较小,值得临床推广应用。     

吡柔比星与表柔比星膀胱灌注预防浅表膀胱癌术后复发的疗效比较及护理体会

目的探讨吡柔比星与表柔比星膀胱灌注预防浅表膀胱癌术后复发的疗效比较及护理体会.方法 选择68例浅表膀胱移行细胞癌患者,随机分为吡柔比星组和表柔比星组.分别予以吡柔比星或表柔比星定期膀胱灌注化疗1年.观察并比较两组患者的复发率、复发时间及并发症的发生率,并回顾了治疗护理方法.结果 随访12～66月,平均34.2±8.4个月,吡柔比星组的复发率明显低于表柔比星组,复发时间明显长于表柔比星组(均P＜0.05).吡柔比星组发生并发症5例,表柔比星组发生并发症3例,两组并发症的的发生率比较无明显的统计学差异(P＞0.05).两组患者治疗期间复查血常规、肝肾功能均无明显异常.结论 吡柔比星预防浅表性膀胱移行细胞癌术后复发的疗效优于表柔比星,不良反应较少,而配合相应的心理护理、术后规律的灌注化疗,可取得较满意疗效.     

多西他赛联合表柔比星治疗乳腺癌

目的观察多西他赛与表柔比星联合辅助化疗治疗乳腺癌的临床疗效。方法从我院收治入院的乳腺癌拟行化疗患者中抽取60例,随机分为观察组与对照组,观察组使用多西他赛与表柔比星联合化疗,对照组使用表柔比星、氟尿嘧啶与环磷酰胺联合化疗,对比观察两组患者临床疗效。结果观察组患者治疗总有效率明显高于对照组,差异有统计学意义(P<0.05)。结论使多西他赛与表柔比星联合应用,在对乳腺癌患者的化疗中,具有更为显著的临床疗效,且无严重副作用,安全可靠,可以在临床上进一步推广应用。     

新辅助化疗方案TE与FEC治疗局部晚期乳腺癌疗效观察

目的探讨多西他赛联合表柔比星(TE)与环磷酰胺联合表柔比星、氟尿嘧啶(FEC)不同化疗方案治疗局部晚期乳腺癌近期疗效及发生不良反应情况。方法回顾性分析86例Ⅱb-Ⅲc期局部晚期乳腺癌患者资料,随机分组,多西他赛联合表柔比星治疗患者38例为观察组,环磷酰胺联合表柔比星、氟尿嘧啶治疗患者48例为对照组,每化疗2个疗程进行疗效评估及不良反应分析。结果观察组治疗局部晚期乳腺癌总有效率89.47%,对照组70.83%,两组之间比较有显著性差异(P<0.05);化疗不良反应以脱发、恶心呕吐、中性粒细胞减少症发生率高,但两组间比较无显著性差异(P>0.05)。结论多西他赛联合表柔比星方案治疗局部晚期乳腺癌的新辅助化疗中,临床近期疗效显著。     

中药与多柔比星化疗联合运用的增效减毒作用

摘 要多柔比星作为蒽环类药物的一员,被广泛应用于肿瘤化疗中,但其明显的心脏毒性及细胞毒性作用在一定程度上限制了其运用。如何提高多柔比星化疗效果及减轻其不良反应是目前值得探索的课题。本文试图从临床和实验的角度,对新近15年来中药与多柔比星联合运用方面的研究进展进行评析,以为临床运用提供参考。     

Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma

Pegylated liposomal doxorubicin (Caelyx?, Doxil?) represents an improved formulation of conventional doxorubicin, with reduced cardiotoxicity and an improved pharmacokinetic profile. This article reviews the efficacy and tolerability of pegylated liposomal doxorubicin in metastatic breast cancer, progressive ovarian cancer, relapsed or refractory multiple myeloma and AIDS-related Kaposi's sarcoma, as well as summarizing its pharmacological properties. In three randomized, open-label, multicentre trials, monotherapy with pegylated liposomal doxorubicin was as effective as doxorubicin or capecitabine in the first-line treatment of metastatic breast cancer, and as effective as vinorelbine or combination mitomycin plus vinblastine in taxane-refractory metastatic breast cancer. Pegylated liposomal doxorubicin alone was as effective as topotecan or gemcitabine alone in patients with progressive ovarian cancer resistant or refractory to platinum- or paclitaxel-based therapy, according to the results of three randomized multicentre trials. In addition, in patients with progressive ovarian cancer who had received prior platinum-based therapy, progression-free survival was significantly longer with pegylated liposomal doxorubicin plus carboplatin than with paclitaxel plus carboplatin, according to the results of a randomized, open-label multicentre trial. Combination therapy with pegylated liposomal doxorubicin plus bortezomib was more effective than bortezomib alone in patients with relapsed or refractory multiple myeloma, according to the results of a randomized, open-label, multinational trial. Randomized multinational trials also demonstrated the efficacy of pegylated liposomal doxorubicin in patients with advanced AIDS-related Kaposi's sarcoma. Pegylated liposomal doxorubicin exhibited a relatively favourable safety profile compared with conventional doxorubicin and other available chemotherapy agents. The most common treatment-related adverse events included myelosuppression, palmar-plantar erythrodysesthesia and stomatitis, although these are manageable with appropriate supportive measures. To conclude, pegylated liposomal doxorubicin is a useful option in the treatment of various malignancies, including metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma.     

Role of pegylated liposomal doxorubicin (Caelyx) in the treatment of relapsing ovarian cancer

The most significant factor predicting response to second-line chemotherapy is the time interval elapsed from the end of chemotherapy to relapse occurrence. Two types of situations may be considered: patients with platinum-sensitive relapse (relapse-free interval longer than 6 months) and patients with platinum-refractory relapse (progression during treatment or relapse-free interval under 6 months). Pegylated liposomal doxorubicin is a doxorubicin formulation. Encapsulation in liposomes confers it different pharmacokinetic characteristics and a more favorable toxicity profile. The following review examines the efficacy and safety of pegylated liposomal doxorubicin for the treatment of relapsing epithelial ovarian cancer.     

Doxorubicin liposomal pegylated: new preparation. Breast cancer: not just a question of short-term cardiac effects

(1) There is no reference first-line chemotherapy regimen for metastatic breast cancer. Anthracycline-based combinations are generally used. One of the main problems with anthracyclines is the risk of heart failure, both during and some time after treatment. (2) A liposomal pegylated doxorubicin, an anthracycline, is now available in Europe. The aim of pegylation is supposedly to reduce the cardiotoxicity relative to standard doxorubicin. The marketing licence specifies that liposomal pegylated doxorubicin must not be used in combination with other drugs in people with metastatic breast cancer. This is the second liposomal doxorubicin preparation to be authorised for this use in France; we concluded that the first product, a non-pegylated form, offered no therapeutic advance. (3) According to the only available comparative trial, liposomal pegylated doxorubicin is no more effective than standard doxorubicin in terms of the duration or quality of survival. (4) In this trial, liposomal pegylated doxorubicin was associated with slightly fewer cardioechographic abnormalities than standard doxorubicin. (5) Other adverse events were also less common (hair loss, nausea and vomiting, and neutropenia), while some were more common (palmoplantar erythrodysesthesia, stomatitis and mucitis). Overall, 24% of patients stopped using liposomal pegylated doxorubicin because of adverse events, compared with 11% of patients receiving standard doxorubicin. (6) Unlike liposomal non-pegylated doxorubicin, the liposomal pegylated form is no more difficult than standard doxorubicin to prepare for injection. (7) In practice, when the decision is made to use doxorubicin, the standard form, at an appropriate dose, is suitable for most patients, as long as cardiac function is closely monitored. Differences in the adverse effect profile (especially hair loss) may make liposomal pegylated doxorubicin more attractive to some patients (it costs 20 times more than standard doxorubicin in France).     

Liposomal doxorubicin in breast cancer: new preparation. Much ado about nothing

(1) There is no reference first-line cytotoxic chemotherapy protocol for metastatic breast cancer, but anthracycline combinations are commonly used. In addition to their myelotoxicity, anthracyclines can cause heart failure, both problems during and after treatment. (2) A liposomal formulation of doxorubicin, an anthracycline, has been developed with the aim of reducing this cardiotoxicity. The marketing terms specify that it must be used in combination with cyclophosphamide, in the first-line treatment of metastatic breast cancer. (3) According to the current evaluation file, which chiefly includes data from three comparative trials, liposomal doxorubicin is no more effective, in terms of the duration or quality of survival, than standard doxorubicin or epirubicin. (4) During comparative trials of liposomal doxorubicin, alone or in combination with cyclophosphamide, signs of cardiotoxicity, as measured by ultrasound, were slightly less frequent than with standard doxorubicin but no less frequent than with epirubicin. Given the possibility of late cardiac events, which were not studied in these trials, there is no evidence that liposomal doxorubicin is really less cardiotoxic than either standard doxorubicin or epirubicin. As regards other adverse effects, liposomal doxorubicin has no advantages over standard doxorubicin or epirubicin. (5) Liposomal doxorubicin is far more difficult to prepare than standard doxorubicin. (6) In France, liposomal doxorubicin is about 15 times more expensive than standard doxorubicin and 4 times more expensive than epirubicin. (7) In practice, standard doxorubicin can still be used, at doses appropriate for the individual patient and with cardiac monitoring.     

Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies

Pegylated liposomal doxorubicin (doxorubicin HCl liposome injection; Doxil or Caelyx) is a liposomal formulation of doxorubicin, reducing uptake by the reticulo-endothelial system due to the attachment of polyethylene glycol polymers to a lipid anchor and stably retaining drug as a result of liposomal entrapment via an ammonium sulfate chemical gradient. These features result in a pharmacokinetic profile characterised by an extended circulation time and a reduced volume of distribution, thereby promoting tumour uptake. Preclinical studies demonstrated one- or two-phase plasma concentration-time profiles. Most of the drug is cleared with an elimination half-life of 20-30 hours. The volume of distribution is close to the blood volume, and the area under the concentration-time curve (AUC) is increased at least 60-fold compared with free doxorubicin. Studies of tissue distribution indicated preferential accumulation into various implanted tumours and human tumour xenografts, with an enhancement of drug concentrations in the tumour when compared with free drug. Clinical studies of pegylated liposomal doxorubicin in humans have included patients with AIDS-related Kaposi's sarcoma (ARKS) and with a variety of solid tumours, including ovarian, breast and prostate carcinomas. The pharmacokinetic profile in humans at doses between 10 and 80 mg/m(2) is similar to that in animals, with one or two distribution phases: an initial phase with a half-life of 1-3 hours and a second phase with a half-life of 30-90 hours. The AUC after a dose of 50 mg/m(2) is approximately 300-fold greater than that with free drug. Clearance and volume of distribution are drastically reduced (at least 250-fold and 60-fold, respectively). Preliminary observations indicate that utilising the distinct pharmacokinetic parameters of pegylated liposomal doxorubicin in dose scheduling is an attractive possibility. In agreement with the preclinical findings, the ability of pegylated liposomes to extravasate through the leaky vasculature of tumours, as well as their extended circulation time, results in enhanced delivery of liposomal drug and/or radiotracers to the tumour site in cancer patients. There is evidence of selective tumour uptake in malignant effusions, ARKS skin lesions and a variety of solid tumours. The toxicity profile of pegylated liposomal doxorubicin is characterised by dose-limiting mucosal and cutaneous toxicities, mild myelosuppression, decreased cardiotoxicity compared with free doxorubicin and minimal alopecia. The mucocutaneous toxicities are dose-limiting per injection; however, the reduced cardiotoxicity allows a larger cumulative dose than that acceptable for free doxorubicin. Thus, pegylated liposomal doxorubicin represents a new class of chemotherapy delivery system that may significantly improve the therapeutic index of doxorubicin.     

Liposomal doxorubicin and weekly paclitaxel in the treatment of metastatic breast cancer

The combination of paclitaxel and doxorubicin or epirubicin is highly active against metastatic breast cancer, yet may produce congestive heart failure. Liposome-encapsulated doxorubicin is a new formulation of doxorubicin with no dose-limiting cardiac toxicity. Twenty-one patients with metastatic breast cancer were treated with pegylated liposomal doxorubicin (20 mg/m2, day 1) and paclitaxel (100 mg/m2, days 1 and 8) for six cycles every 2 weeks. All patients had had relapse or progression on one to five previous chemotherapies. We observed two patients with complete and eight patients with partial remissions (48% response rate). Eight of the 10 responders had had previous therapy with epirubicin, doxorubicin or mitoxantrone. The mean remission duration was 5 months. Disease progression due to brain metastasis occurred in five cases. Severe side effects (grade 3 WHO) were alopecia (100%), skin toxicity in 29%, neuropathy in 24% and mucositis in 13%. Leukopenia (grade 4 WHO) was observed in 48%, but there was no cardiac toxicity, no death and no hospitalization. The combination of weekly paclitaxel and liposomal doxorubicin every 2 weeks is highly effective in previously treated patients. Based on the doses we administered, we recommend 15 mg/m2 liposomal doxorubicin every 2 weeks and 80 mg/m2 paclitaxel weekly.     

Pegylated liposomal doxorubicin in the treatment of cancers of the breast and ovary

Peglyated liposomal doxorubicin was developed to maintain or enhance the demonstrated antineoplastic effects of doxorubicin, while improving the toxicity profile associated with this important cytotoxic agent. Accumulating clinical data have confirmed the activity of pegylated liposomal doxorubicin in cancers of the breast and ovary. Furthermore, Phase II and III trial experience has revealed that the drug produces objective responses comparable in rate and duration to doxorubicin and other single agents employed in metastatic breast cancer. In recurrent and platinum-resistant ovarian cancer, single-agent pegylated liposomal doxorubicin has assumed an important role in routine patient management.     

Pegylated liposomal doxorubicin in the treatment of cancers of the breast and ovary

Peglyated liposomal doxorubicin was developed to maintain or enhance the demonstrated antineoplastic effects of doxorubicin, while improving the toxicity profile associated with this important cytotoxic agent. Accumulating clinical data have confirmed the activity of pegylated liposomal doxorubicin in cancers of the breast and ovary. Furthermore, Phase II and III trial experience has revealed that the drug produces objective responses comparable in rate and duration to doxorubicin and other single agents employed in metastatic breast cancer. In recurrent and platinum-resistant ovarian cancer, single-agent pegylated liposomal doxorubicin has assumed an important role in routine patient management.     

Enhanced tumor delivery and antitumor activity in vivo of liposomal doxorubicin modified with MCF-7-specific phage fusion protein

A novel strategy to improve the therapeutic index of chemotherapy has been developed by the integration of nanotechnology with phage technique. The objective of this study was to combine phage display, identifying tumor-targeting ligands, with a liposomal nanocarrier for targeted delivery of doxorubicin. Following the proof of concept in cell-based experiments, this study focused on in vivo assessment of antitumor activity and potential side-effects of phage fusion protein-modified liposomal doxorubicin. MCF-7-targeted phage-Doxil treatments led to greater tumor remission and faster onset of antitumor activity than the treatments with non-targeted formulations. The enhanced anticancer effect induced by the targeted phage-Doxil correlated with an improved tumor accumulation of doxorubicin. Tumor sections consistently revealed enhanced apoptosis, reduced proliferation activity and extensive necrosis. Phage-Doxil-treated mice did not show any sign of hepatotoxicity and maintained overall health. Therefore, MCF-7-targeted phage-Doxil seems to be an active and tolerable chemotherapy for breast cancer treatment.From the Clinical EditorThe authors of this study successfully combined phage display with a liposomal nanocarrier for targeted delivery of doxorubicin using MCF-7-targeted phage-Doxil nanocarriers in a rodent model. The method demonstrated improved efficiency and reduced hepatotoxicity, paving the way to future clinical trials addressing breast cancer.