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。     

Prevention and treatment of doxorubicin-induced cardiotoxicity by dexrazoxane and schisandrin B in rabbits

The cost of dexrazoxane, a drug used to provide protection from doxorubicin-induced cardiotoxicity, limits its use in low-income countries. We aimed to see whether schisandrin B, an inexpensive drug, could provide protection equivalent to that provided by dexrazoxane. New Zealand white rabbits were randomly divided into groups and treated with saline, doxorubicin, doxorubicin + dexrazoxane, or doxorubicin + schisandrin B. Doxorubicin-induced damage and the protective effects were studied by recording the echocardiographic parameters and serum levels of superoxide dismutase, malondialdehyde, cardiac troponin I, and brain natriuretic peptide and observing the histology and degree of apoptosis. Schisandrin B had dose-dependent effects in decreasing the magnitude of doxorubicin-induced indicators of cardiomyopathy to a degree that approximated the decrease produced by dexrazoxane treatment. Schisandrin B might be a useful, low-cost alternative drug for this application.     

阿霉素脂质体对克服肿瘤多药耐药的细胞学体外评价

目的:评价市售阿霉素脂质体体外逆转肿瘤多药耐药(MDR)的作用。方法:MTT法比较阿霉素和阿霉素脂质体体外对敏感和耐药细胞的细胞毒作用;荧光显微镜观察2组药物对敏感和耐药细胞的影响;流式细胞仪检测2组分别在细胞内的积累和外排情况。结果:细胞毒性试验结果显示,尽管在敏感细胞中,阿霉素脂质体IC50远高于阿霉素溶液组,对于耐药细胞株,阿霉素脂质体的IC50与游离阿霉素无显著性差异(P>0.05);细胞荧光染色显示,阿霉素脂质体较溶液在耐药细胞核中有更强的红染;细胞摄取试验显示,相同浓度下,阿霉素脂质体较溶液组在耐药细胞中积累量差异无显著性(P>0.05),但外排试验显示,在耐药细胞KBv200中,相同浓度下的脂质体较溶液具有更强的细胞滞留能力(P<0.05)。结论:阿霉素脂质体较阿霉素溶液在体外能更多进入耐药细胞核,并表现出更强的药物滞留能力,可部分克服多药耐药。     

Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats

BACKGROUND AND PURPOSE: Doxorubicin causes a chronic cardiomyopathy in which reactive oxygen species (ROS) accumulate over time and are associated with genetic and functional lesions of mitochondria. Dexrazoxane is a cardioprotective iron chelator that interferes with ROS production. We aim to analyze the effects of dexrazoxane on mitochondria in the prevention of doxorubicin-induced chronic myocardial lesions. EXPERIMENTAL APPROACH: Wistar rats (11 weeks of age) were injected with intravenous doxorubicin (0.8 mg kg(-1) weekly for 7 weeks) with or without simultaneous dexrazoxane (8 mg kg(-1)). Animals were killed at 48 weeks. Cardiomyopathy was scored clinically and histologically and cardiac mitochondria were analyzed. KEY RESULTS: Compared to control rats receiving saline, rats treated with doxorubicin alone developed a clinical, macroscopic, histological and ultrastructural cardiomyopathy with low cytochrome c-oxidase (COX) activity (26% of controls). The expression of the mtDNA-encoded COX II subunit was reduced (64% of controls). Myocardia exhibited a high production of ROS (malondialdehyde 338% and superoxide 787% of controls). Mitochondria were depleted of mitochondrial DNA (mtDNA copy number 46% of controls) and contained elevated levels of mtDNA deletions. Dexrazoxane co-administration prevented all these effects of doxorubicin on mitochondria, except that hearts co-exposed to doxorubicin and dexrazoxane had a slightly lower mtDNA content (81% of controls) and mtDNA deletions at low frequency. CONCLUSIONS AND IMPLICATIONS: Dexrazoxane prevented doxorubicin induced late-onset cardiomyopathy and also protected the cardiac mitochondria from acquired ultrastructural, genetic and functional damage.     

The antitumor anthracyclines doxorubicin and daunorubicin do not inhibit cell growth through the formation of iron-mediated reactive oxygen species

The use of the anthracycline anticancer drugs doxorubicin and daunorubicin is limited by what is thought to be an iron-based oxygen radical-derived dose-dependent cardiotoxicity. The anthracyclines are also DNA topoisomerase (Topo) II poisons. It is not known if iron-mediated formation of reactive oxygen species (ROS) by the anthracyclines or their Topo II inhibitory effects are responsible for their cell growth-inhibitory effects. Experiments to test these two alternatives were carried out using a CHO-derived cell line (DZR) that was highly resistant to dexrazoxane through a Thr48IIe mutation in Topo IIalpha. The clinically used cardioprotective agent dexrazoxane likely exerts its cardioprotective effects through the chelating ability of its hydrolysis product ADR-925, an analog of EDTA. Dexrazoxane is also a cell growth inhibitor that acts through its ability to inhibit the catalytic activity of Topo II. Thus, the DZR cell line allowed us to examine the cell growth-inhibitory effects of doxorubicin and daunorubicin in the presence of dexrazoxane without the confounding effect of dexrazoxane inhibiting cell growth. The growth-inhibitory effects of neither doxorubicin nor daunorubicin were affected by pretreating DZR cells with dexrazoxane. In contrast, under similar conditions, dexrazoxane strongly protected rat cardiac myocytes from doxorubicin-induced lactate dehydrogenase release. In conclusion, the anthracyclines do not inhibit the growth of DZR cells through the generation of iron-mediated formation of ROS.     

Comparative open, randomized, cross-over bioequivalence study of two intravenous dexrazoxane formulations (Cardioxane and ICRF-187) in patients with advanced breast cancer, treated with 5-fluorouracil-doxorubicin-cyclophosphamide (FDC).

The purpose of this study was to compare the pharmacokinetic disposition of two intravenous dexrazoxane formulations, and their effects on doxorubicin's kinetics and metabolism. Plasma concentration versus time curves and pharmacokinetic parameters of dexrazoxane given as Cardioxane (dexrazoxane hydrochloride salt) and ICRF-187 reference formulation (dexrazoxane base) were determined and compared. Both formulations were administered as a single intravenous infusion prior to 5-fluorouracil-doxorubicin-cyclophosphamide administration. In addition, the pharmacokinetics of doxorubicin and its metabolites were studied after dexrazoxane administration. A total of 15 patients with advanced breast cancer participated in this open, randomized, cross-over study and 12 patients were evaluable. Plasma concentrations of dexrazoxane, doxorubicin and doxorubicin metabolites were determined by high-performance liquid chromatography in samples obtained in the 72 h after drug administration. No statistically significant differences were found in the tested kinetic parameters when the two products were compared by analysis of variance (ANOVA) on log-transformed data. Cardioxane fulfilled the bioequivalence criteria when compared with ICRF-187 reference formulation for all of the investigated parameters (AUC, t1/2beta, Vdss, Cl(tot), Cl(ren)). The parametric 90% confidence intervals were contained within the bioequivalence interval (0.8-1.25). Pharmacokinetic parameters and metabolism of doxorubicin were not different after the administration of either Cardioxane or ICRF-187 formulation. From the results of this study it can be concluded that the two formulations can be considered bioequivalent with regard to extent of absorption (AUC and Vdss) and elimination (t1/2beta, Cl(tot) and Cl(ren)).     

黄芪注射液/华蟾素注射液联合右丙亚胺对阿霉素相关性心脏毒性的保护作用

目的:探讨黄黄芪注射液/华蟾素注射液联合右丙亚胺对阿霉素相关性心脏毒性的保护作用,并与单用右丙亚胺对比研究。方法:120例采用含阿霉素化疗方案首次治疗的恶性肿瘤患者随机分为:A组:右丙亚胺组;B组:右丙亚胺与黄芪注射液联合治疗;C组:右丙亚胺与华蟾素注射液联合治疗组;D组:右丙亚胺与黄芪注射液及华蟾素注射液联合治疗组(每组各30例)。A组常规化疗前给予右丙亚胺静脉输注,B组常规化疗前给予右丙亚胺与黄芪联合治疗,C组常规化疗前给予右丙亚胺与华蟾素联合治疗,D组常规化疗前给予右丙亚胺、黄芪及华蟾素联合治疗,共4个周期。比较4组患者治疗前后心电图、肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白Ⅰ(cTnⅠ),左室舒张末期内径(LVIDD),左射血分数(EF)。结果:经4个周期治疗后,D组无论是心电图异常发生率还是CK-MB、cTnⅠ、LVIDD、EF与另三组比较差异均有显著性(P < 0.05);而A、B、C 3组间患者的心电图异常发生率、CK-MB、cTnⅠ、LVIDD、EF无显著性差异(P > 0.05)。结论:黄芪和华蟾素注射液联合右丙亚胺可减低阿霉素所致心脏毒性作用,优于单用右丙亚胺。     

Self-assembled peptide (CADY-1) improved the clinical application of doxorubicin

CADY-1 is an amphipathic peptide that possesses cell-penetrating activity. As an amphipathic peptide, CADY-1 is capable of forming complexes by self-assembly, and they are these complexes that possess cell-penetrating activity. This distinct characteristic of CADY-1 makes it a potent cell-penetrating drug delivery system. Doxorubicin is a widely used cytotoxic anti-cancer drug but is limited by its toxicity. Although the liposomal formulation of doxorubicin ameliorates its toxicity, its complicated synthesis remains an obstacle to its wide clinical use. In this study, our findings revealed that CADY-1 and doxorubicin form a stable complex at optimised molar ratios in a self-assembling manner. Formation of the complex extended the blood residence time of doxorubicin in a similar fashion to that of liposomal doxorubicin. In addition, the complex was capable of carrying doxorubicin across the cell membrane, which increased the therapeutic index of doxorubicin. Experimental animals treated with a CADY-1/doxorubicin complex exhibited better tolerance and anti-tumour activity than animals treated with either liposomal doxorubicin or the free form of doxorubicin. Collectively, the findings in this study support the advantages of using complexes formed by the self-assembled peptide CADY-1 and suggest that CADY-1 is a potent drug delivery system.     

A murine experimental anthracycline extravasation model: Pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

The bisdioxopiperazine topoisomerase II catalytic inhibitor dexrazoxane has successfully been introduced into the clinic as an antidote to accidental anthracycline extravasation based on our preclinical mouse studies. The histology of this mouse extravasation model was investigated and found to be similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing with dense dermal connective tissue. The extension of this fibrosis was quantified, and dexrazoxane intervention resulted in a statistically significant decrease in fibrosis extension, as also observed in the clinic. Several mechanisms have been proposed in anthracycline extravasation cytotoxicity, and we tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe²⁺ complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity of topoisomerase II alpha and thereby prevents access of anthracycline to the enzyme and thus cytotoxicity, and also acts as a strong iron chelator following opening of its two bisdioxopiperazine rings. Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation in the topoisomerase II alpha gene (Top2a^Y165S/+), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Thus, interaction with topoisomerase II alpha is not central in the pathogenesis of anthracycline-induced skin damage. In contrast to dexrazoxane, the iron-chelating bisdioxopiperazine ICRF-161 do not inhibit the catalytic cycle of topoisomerase II alpha. This compound was used to isolate and test the importance of iron in the wound pathogenesis. ICRF-161 was found ineffective in the treatment of anthracycline-induced skin damage, suggesting that iron does not play a dominant role in the genesis of wounds.     

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.     

Activity of Dexrazoxane and Amifostine Against Late Cardiotoxicity Induced by the Combination of Doxorubicin and Cyclophosphamide In Vivo

Cardiotoxicity is one of the main limiting side effects of doxorubicin and cyclophosphamide (DC) treatment, and this study was organized to identify cardioprotective activity of amifostine and dexrazoxane against DC combination. BalbC/NIH mice underwent DC treatment (DC group), were pre‐treated with amifostine (ADC group) or dexrazoxane (IDC group) and were killed at 1.5 and 3 months after treatments when the grade of myocardial damage was analysed by light microscopy using the Billingham scoring method. DC treatment induced severe myocardial damage with one lethal event before evaluation at 3 months. Main characteristics of DC cardiotoxicity were polymorphic myocyte degeneration and alterations in blood vessels followed by ecchymoses, haemorrhage and thromboses. Polymorphism was also found in the IDC and ADC groups, but its morphological patterns were different. In animals subject to IDC treatment, the blood vessels were better preserved than in the ADC group, whereas thrombosis was not seen in either of these two groups. Quantitatively, grade of myocardial injury in the ADC and IDC groups was significantly higher compared with the non‐treated group at both times of estimation and significantly lower compared with the DC group at 1.5 months. At 3 months, significance against DC treatment was lost in the ADC group, while preserved in the IDC‐treated animals. Also, there was significant progression in the ADC group comparing scores between 1.5 and 3 months. These results revealed that the cardiotoxicity of DC combination displays specific morphological hallmark and evolution in time, different to those described after doxorubicin single treatment. Neither amifostine nor dexrazoxane prevented development of cardiomyopathy induced by DC treatment.     

Encapsulation of doxorubicin in liposomes containing phospatidylethanol. Part III: Effect on the toxicity and accumulation of antibiotic in myocardium

The toxicity of sterically stabilized doxorubicin-containing “solid” liposomes comprising a mixture of distearoyl analogs of phospatidylcholine and phosphatidylethanol (in a 3: 2 molar ratio) was evaluated. Upon infusion of the ordinary and liposomal doxorubicin in a total dose of 12 mg/kg, the early loss of mice with implanted ascitic Ehrlich’s carcinoma was 100 and 50%, respectively, and the average lifetime of the animals treated with liposomal doxorubicin was 1.6 times longer. In comparison to the ordinary doxorubicin, administration of the liposomal preparation resulted in a lower drop of the body weight (10%) and a smaller decrease in leukocyte number (12%). The results of fluorimetric measurements showed that the accumulation of antibiotic in the cardiac muscle 15–180 min after infusion of the liposomal doxorubicin was 30–57% lower than that upon infusion of the ordinary preparation. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 36–38, March, 2006.     

Experimental study of dexrazoxane-anthracycline combinations using the model of isolated perfused rat heart

We have studied the protective effect of dexrazoxane on the cardiac toxicity induced by the anthracyclines currently used in clinics, doxorubicin, epirubicin, daunorubicin and idarubicin, with special emphasis on determining the optimal dose of dexrazoxane. This was performed using the model of isolated perfused rat heart after 12-day combination treatment of anthracyclines used at equi-cardiotoxic doses, and dexrazoxane used at 10-fold or 20-fold the anthracycline dose. We have shown in this study that dexrazoxane by itself was not cardiotoxic, and was able to significantly reduce anthracycline cardiac toxicity without increasing the general toxicity induced by these drugs. Using dexrazoxane at 20 times the anthracycline dose provided a better cardioprotection than using it at 10 times the anthracycline dose; at the higher dexrazoxane dose, the functional cardiac parameters (developed pressure, contractility and relaxation) were not different from those recorded in control animals.     

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.     

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).     

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。     

Development of the model of rat isolated perfused heart for the evaluation of anthracycline cardiotoxicity and its circumvention.

1. In order to develop a predictive model for the preclinical evaluation of anthracycline cardiotoxicity and the means of preventing it, we have studied the functional parameters of perfused hearts isolated from rats receiving repeated doses of several anthracyclines. 2. The anthracyclines studied were doxorubicin, epirubicin, pirarubicin and daunorubicin, and we also studied a liposomal formulation of daunorubicin (DaunoXome) and the co-administration of dexrazoxane (ICRF-187) and doxorubicin. 3. Anthracyclines were administered i.p. at equimolar doses corresponding to 3 mg kg-1 per injection of doxorubicin, every other day for a total of six doses. Dexrazoxane was used at the dose of 30 mg kg-1 per injection and was administered either 30 min before or 30 min after doxorubicin. We evaluated any general toxicity towards the animals as well as alterations of left ventricular contractility and relaxation ex vivo. 4. Epirubicin and daunorubicin were significantly less cardiotoxic than doxorubicin, and neither pirarubicin nor DaunoXome caused significant alterations in cardiac function. There was a direct relationship between the decrease in cardiac contractility or relaxation and anthracycline accumulation in the heart, evaluated after the same treatment schedule. 5. Dexrazoxane induced a significant protection against doxorubicin-induced cardiac toxicity when administered 30 min before doxorubicin, whereas this protection was ineffective when administered 30 min after doxorubicin. Direct perfusion of DaunoXome in isolated hearts of untreated animals resulted in a 12-fold reduction of the accumulation of daunorubicin in heart tissue as compared to the perfusion of free daunorubicin, and did not cause alterations in cardiac function at a dosage for which free daunorubicin induced major alterations. 6. The isolated perfused rat heart appears to be a valuable model for screening of new anthracyclines and of strategies for circumventing anthracycline cardiotoxicity.     

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.