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Liposomal Anthracyclines in Metastatic Breast Cancer: Clinical Update

Department of Breast Medical Oncology, Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

Correspondence: Edgardo Rivera, M.D., Department of Medical Oncology, Unit 424, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030-4009, USA. Telephone: 713-792-2817; Fax: 713-794-4385; e-mail: erivera{at}mail.mdanderson.org

	LEARNING OBJECTIVES

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
After completing this course, the reader will be able to:

1. Differentiate liposomal anthracycline formulations.
   
2. Describe the efficacies and tolerabilities of liposomal anthracyclines as single agents and in combination therapy in the treatment of metastatic breast cancer.
   
3. Compare the efficacies and tolerabilities of liposomal anthracyclines with those of conventional anthracyclines.
   

	ABSTRACT

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
Anthracyclines are a mainstay of therapy for patients with metastatic breast cancer. However, their use has been limited by associated toxicities, including myelosuppression, alopecia, nausea and vomiting, stomatitis, and most importantly, cardiotoxicity. Liposomal anthracyclines were developed to increase the therapeutic index of conventional anthracyclines by maintaining antitumor efficacy while improving the safety profile. There are currently three liposomal formulations: liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin. Only one phase I study has been conducted with liposomal daunorubicin for metastatic breast cancer. Liposomal doxorubicin has shown comparable efficacy with conventional doxorubicin and less toxicity. Pegylated liposomal doxorubicin is the most widely studied of the liposomal anthracyclines and has demonstrated similar efficacy to conventional doxorubicin and a better safety profile, including significantly less cardiotoxicity, in patients with metastatic breast cancer. Pegylated liposomal doxorubicin has shown efficacy as a single agent and in combination with many agents, including cyclophosphamide, paclitaxel, docetaxel, and gemcitabine, with response rates ranging from 33%-75%. Growing evidence supports the use of pegylated liposomal doxorubicin as first-line treatment for patients with metastatic breast cancer, owing to its antitumor activity in both anthracycline-naïve patients and in patients with previous anthracycline exposure.

Key Words. Anthracyclines • Liposome • Doxorubicin • Breast neoplasms • Neoplasm metastasis • Clinical trials

	INTRODUCTION

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
Anthracyclines are among the most widely used agents to treat breast cancer—not only in the adjuvant setting, but also for the treatment of patients with metastatic disease. Considered a mainstay of therapy, doxorubicin-based regimens have demonstrated benefits in terms of response rate, time to disease progression, and overall survival. It is still controversial whether patients with metastatic breast cancer (MBC) have better outcomes with combination versus single-agent therapy. A recent phase III trial compared a combined conventional doxorubicin and paclitaxel regimen with the same agents given sequentially in patients with MBC [1]. Although the response rates and progression-free survival rate were both greater in patients receiving combination therapy, combination therapy did not improve overall survival or quality of life [1]. Moreover, the most recent National Comprehensive Cancer Network (NCCN) guidelines state that there is no compelling evidence that combination regimens are superior to sequential single agents [2].

Despite its excellent antitumor activity, conventional doxorubicin has a relatively low therapeutic index, and its use is limited by the development of myelosuppression, alopecia, acute nausea and vomiting, stomatitis, and cumulative cardiotoxicity. Although cardiotoxicity associated with conventional doxorubicin usually occurs as an acute or subacute syndrome, myocardial damage may occur, particularly in patients with greater drug exposure [3]. Thus, it is recommended that the cumulative lifetime dose of conventional doxorubicin not exceed 450-550 mg/m² [4, 5]. The use of conventional doxorubicin is also not generally recommended in patients with greater risks of developing cardiac toxicity, such as those with preexisting cardiac disease, those with a history of mediastinal irradiation, and the elderly [3, 6]. Conventional doxorubicin should be used cautiously in young patients, as it may compromise their long-term quality of life. It appears that conventional anthracyclines cannot be combined safely with newer targeted agents, such as trastuzumab, due to an unacceptable risk for developing cardiotoxicity with this combination [7].

Several liposomal anthracycline formulations have been developed to increase the therapeutic index of conventional anthracyclines. This paper reviews the published literature on these agents, both as single-agent therapy and in combination with other treatment modalities.

	LIPOSOMAL ANTHRACYCLINES

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
The goal of liposomal encapsulation of anthracyclines is to alter tissue distribution and pharmacokinetics, thereby improving the therapeutic index of these agents. To date, three liposomal anthracycline formulations have been developed: liposomal daunorubicin (DaunoXome^®; Gilead Sciences, Inc.; San Dimas, CA; http://www.gilead.com), liposomal doxorubicin (D-99, Myocet^TM; Elan Pharmaceuticals; Princeton, NJ; http://www.elan.com), and pegylated liposomal doxorubicin (Doxil^® is marketed and distributed in the U.S. by Ortho Biotech Products, L.P., Bridgewater, NJ; http://www.orthobiotech.com; Caelyx^® is marketed outside the U.S. by Schering-Plough Corporation, Kenilworth, NJ; http://www.schering-plough.com). Some important differences exist among these agents (Fig. 1). First, there is a substantial difference in half-life, ranging from approximately 2-4 hours for liposomal daunorubicin and liposomal doxorubicin formulations to over 55 hours for pegylated liposomal doxorubicin [8–10]. In addition, pegylated liposomal doxorubicin is the only liposomal anthracycline that exhibits drastically lower uptake by the mononuclear phagocyte system, due to an additional polyethylene glycol layer that surrounds the doxorubicin-containing liposome, thereby resulting in a greater plasma half-life relative to other liposomal anthracyclines. The size of these drug-containing vesicles allows the liposomes to extravasate through the leaky tumor vasculature. This property, combined with the longer half-life, promotes targeted drug delivery to the tumor site [11].

View larger version (29K): [in this window] [in a new window]   Figure 1. Comparison of liposomal anthracycline formulations. *Pegylated liposomal doxorubicin is the only liposomal anthracycline that undergoes pegylation, which extends the drug half-life (t1/2) and allows it to avoid the immune system and more effectively target the tumor [8–10].

Liposomal Doxorubicin (D-99)
Liposomal doxorubicin (D-99) is approved in the European Union as part of a combined first-line treatment regimen (with cyclophosphamide) for MBC [9] and is currently under investigation in the U.S. for the treatment of breast cancer, myeloma, and Kaposi’s sarcoma. Several studies have evaluated the efficacy and safety of liposomal doxorubicin in patients with MBC [13–16].

Two studies compared the liposomal formulation with conventional doxorubicin, and no differences in terms of response rate were reported (Table 1). In a phase III study conducted by Harris and colleagues (n = 224), patients received either liposomal doxorubicin, 75 mg/m², or conventional doxorubicin, 75 mg/m², every 3 weeks [13]. Response rates were 26% in both the liposomal and conventional doxorubicin treatment groups, with less toxicity, including cardiotoxicity, in patients receiving the liposomal formulation. A more detailed discussion of the cardiac safety of liposomal doxorubicin is included elsewhere in this supplement [17]. Myelosuppression was the most frequent and severe toxicity in both treatment groups.

Pegylated Liposomal Doxorubicin
Pegylated liposomal doxorubicin is currently approved in the U.S. for the treatment of paclitaxel- and platinum-refractory metastatic ovarian cancer and AIDS-related Kaposi’s sarcoma [10]. It is also being evaluated in several other tumor types, including breast cancer, multiple myeloma, non-Hodgkin’s lymphoma, and gynecologic malignancies. When compared with other liposomal anthracycline formulations, pegylated liposomal doxorubicin is the most extensively studied in patients with MBC. Pegylated liposomal doxorubicin has demonstrated antitumor activity and safety in patients with MBC, leading to its recent approval in the European Union as monotherapy for MBC in patients who have greater cardiac risks, in addition to its compendial listing in the U.S. for patients with MBC.

The efficacy and safety of pegylated liposomal doxorubicin as single-agent therapy for MBC have been investigated in two phase II trials [18, 19]. In the first study, a total of 71 patients with stage IV breast cancer received pegylated liposomal doxorubicin at doses of 45-60 mg/m² every 3-4 weeks for a maximum of six cycles; all patients had received prior nonanthracycline-based chemotherapy [18]. The overall response rate was 31%, and treatment was generally well tolerated. Grade 3 or 4 neutropenia and mucositis were noted in 27% and 32% of patients, respectively; alopecia, cardiotoxicity, and nausea and vomiting were uncommon. Although skin toxicity occurred in 25% of cycles in patients receiving 60 mg/m² every 3 weeks, the incidence was much lower at doses of 45 mg/m² every 4 weeks, with only 5% of treatment cycles affected.

The second study was a dose-ranging trial involving 45 patients with MBC [19]. Patients received pegylated liposomal doxorubicin at doses of 35-70 mg/m² every 3-6 weeks. The overall response rate was 33%, and treatment was generally well tolerated. The development of stomatitis was dose related and occurred at a higher frequency in patients receiving doses 60 mg/m². The incidence of palmar-plantar erythrodysesthesia/hand-foot syndrome (PPE/ HFS) was schedule dependent, with shorter dosing intervals leading to a greater frequency and severity of skin manifestations. Cardiotoxicity was noted in one patient with a history of mitoxantrone treatment and prior mediastinal radiation therapy.

Two phase III studies have compared the efficacy and safety of pegylated liposomal doxorubicin with those of other treatment regimens. Wigler and colleagues compared the efficacy and safety of pegylated liposomal doxorubicin with those of conventional doxorubicin as first-line therapy in patients with advanced MBC [20]. A total of 509 women received 1-hour infusions of either pegylated liposomal doxorubicin, 50 mg/m² once every 4 weeks, or conventional doxorubicin, 60 mg/m² once every 3 weeks. Primary end points were progression-free survival and cardiac safety, while secondary end points included overall survival, response rate, and safety.

Baseline patient characteristics were similar for the two groups, including the number of patients with and their degree of previous anthracycline exposure. The median progression-free survival was similar in both treatment groups: 6.9 months in patients receiving pegylated liposomal doxorubicin versus 7.8 months in patients receiving conventional doxorubicin (p = 0.99). Likewise, overall survival was 20.1 months for patients receiving pegylated liposomal doxorubicin, compared with 22.0 months in those receiving the conventional formulation. The incidences of alopecia, myelosuppression, and nausea and vomiting were lower in patients treated with pegylated liposomal doxorubicin than in patients treated with conventional doxorubicin. Perhaps most notably, pegylated liposomal doxorubicin was associated with a significantly lower incidence of cardiotoxicity, even at higher cumulative doses (p < 0.001) [20]. The cardiac safety profile of pegylated liposomal doxorubicin in that study is discussed in detail elsewhere in this supplement [17].

In another phase III study involving 301 patients with advanced MBC who had failed a prior taxane-containing regimen, Keller and colleagues compared pegylated liposomal doxorubicin, 50 mg/m² every 4 weeks, with the European standard of treatment, either vinorelbine, 30 mg/m² once weekly, or mitomycin C, 10 mg/m² on days 1 and 28, plus vinblastine, 5 mg/m² on days 1, 14, 28, and 42 every 6-8 weeks [21]. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxicity.

In that study, pegylated liposomal doxorubicin demonstrated efficacy similar to that of the comparator regimens. Progression-free survival was similar for the pegylated liposomal doxorubicin and comparator groups (2.86 months versus 2.53 months, respectively). Overall survival was slightly higher with pegylated liposomal doxorubicin (11.0 months versus 9.0 months for the comparator group), although this difference was not statistically significant. The objective response rate was 9% for pegylated liposomal doxorubicin, compared with 11% for the comparator group [21].

	PEGYLATED LIPOSOMAL DOXORUBICIN IN COMBINATION THERAPY

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
Because the efficacies of new chemotherapeutic agents may be further enhanced (in either a synergistic or additive manner) when combined with other agents that have different mechanisms of action and nonoverlapping toxicity profiles, a number of investigators have evaluated the antitumor activity of pegylated liposomal doxorubicin as part of a combined treatment regimen for MBC. Indeed, results of several recent studies have shown that pegylated liposomal doxorubicin is effective in combination with other agents for MBC, including cyclophosphamide [22], paclitaxel [23, 24], docetaxel [25, 26], and gemcitabine [27, 28], with response rates ranging from 33%-75%. The results of those studies are summarized in the following sections.

Pegylated Liposomal Doxorubicin in Combination with Cyclophosphamide
Overmoyer and colleagues evaluated the use of pegylated liposomal doxorubicin in combination with cyclophosphamide as first-line treatment for MBC in a phase Ib dose-ranging study [22]. Based on the activity observed in the first dosing cohort (n = 10; pegylated liposomal doxorubicin, 50 mg/m² i.v. day 1, plus cyclophosphamide, 100 mg/m² orally days 1-14, every 28 days), 20 patients were enrolled in cohort II and received pegylated liposomal doxorubicin, 30 mg/m², plus cyclophosphamide, 600 mg/m² i.v., every 21 days. The most frequently observed adverse events included infusion reactions, neutropenia, PPE/HFS, and stomatitis. An objective response was observed in 7/17 evaluable patients (41%). Given the activity and tolerability observed with this combination, additional patients were enrolled in a third dosing cohort and received cyclophosphamide and a higher dose of pegylated liposomal doxorubicin. The final results from that study have not been reported.

Pegylated Liposomal Doxorubicin in Combination with Paclitaxel
Two phase II studies have investigated the feasibility of combined treatment with pegylated liposomal doxorubicin and paclitaxel [23, 24]. In the first study, 18 patients with advanced MBC received pegylated liposomal doxorubicin, 45 mg/m² every 4 weeks, in combination with paclitaxel, 80 mg/m² weekly [23]. Thirteen patients had received prior adjuvant chemotherapy (seven patients with conventional doxorubicin). In the 12 patients evaluated for efficacy, the response rate was 75%: two patients had complete responses, seven had partial responses, and one patient had stable disease. Sixteen patients were evaluated for safety; grade 3 or 4 neutropenia occurred in 11 patients and grade 3 or 4 mucositis occurred in six patients. Other side effects included fatigue, nausea, diarrhea, and PPE/HFS. No signs of cardiotoxicity were noted.

The second study using this combination involved 35 patients with newly diagnosed, locally advanced breast cancer [24]. In that study, however, patients received pegylated liposomal doxorubicin, 35 mg/m², plus paclitaxel, 175 mg/m², every 3 weeks. The response rate was 71%, with six patients having complete responses and 19 patients having partial responses to treatment. Treatment was generally well tolerated, with grade 3 PPE/HFS occurring in three patients (9%) and grade 3 leukopenia occurring in four patients (11%). Alopecia occurred in 29 patients (83%), which was attributed to paclitaxel. The authors concluded that pegylated liposomal doxorubicin in combination with paclitaxel is an active regimen in patients with locally advanced breast cancer.

Based on the results of these small studies, it appears that the combination of pegylated liposomal doxorubicin and paclitaxel is effective and well tolerated. It remains to be seen whether these high response rates (i.e., >70%) can be replicated in large-scale studies.

Pegylated Liposomal Doxorubicin in Combination with Docetaxel
The first phase I study that evaluated the combination of pegylated liposomal doxorubicin and docetaxel in breast cancer was conducted by Chodkiewicz and colleagues [25]. Both previously treated and untreated patients received pegylated liposomal doxorubicin, 30 mg/m², and docetaxel, 80 mg/m², every 3 weeks, with 5 µg/kg G-CSF on days 3-13 postchemotherapy. Of seven patients treated for breast cancer, three had partial responses and three had stable disease. Grade 3/4 toxicities included neutropenia, thrombocytopenia, skin toxicity, and mucositis. Pharmacokinetic analyses suggested that combination therapy increased tissue retention and decreased clearance of docetaxel.

Sparano and colleagues conducted a phase I dose-escalation study of pegylated liposomal doxorubicin at doses of 30-45 mg/m² in combination with docetaxel at doses of 60-75 mg/m² every 3-4 weeks in patients with locally advanced and MBC (n = 41) [26]. Prior treatments included adjuvant chemotherapy (34% of patients), adjuvant conventional doxorubicin (22%), and chemotherapy for metastatic disease (10%).

Objective responses were observed in 16 of 29 evaluable patients (55%), regardless of dose level. In patients receiving the dose levels recommended for further evaluation (pegylated liposomal doxorubicin, 30 mg/m², plus docetaxel, 60 mg/m², every 21 days), the response rate was 42% (5/12 evaluable patients). The overall median duration of response was 7 months. The median time to progression was 8 months, with a median overall survival of 18 months. At the recommended dose, the most common grade 3/4 toxicities included neutropenia (60%), hyperglycemia (20%), mucositis (13%), PPE/HFS (13%), and anemia (13%). It is likely that the relatively high incidence of neutropenia was due to the docetaxel component of the regimen. There was no clinical evidence of congestive heart failure (CHF). Two patients had an absolute decrease 10% in left ventricular ejection fraction (LVEF) from baseline: LVEF remained above normal in one patient (80% to 65%, cumulative pegylated liposomal doxorubicin dose of 120 mg/m²), and there was an asymptomatic decrease in LVEF from 63% to 47% in another patient (cumulative pegylated liposomal doxorubicin dose of 190 mg/m², prior adjuvant doxorubicin dose of 240 mg/m²) [26]. The promising activity of pegylated liposomal doxorubicin in combination with docetaxel warrants further investigation in a phase II study.

Pegylated Liposomal Doxorubicin in Combination with Gemcitabine
Rivera and colleagues studied pegylated liposomal doxorubicin in combination with gemcitabine in a phase I study to determine the maximum tolerated dose and toxicity profile of this combination [27]. Twenty-seven patients received a fixed dose of gemcitabine (800 mg/m²) on days 1 and 8 and a starting dose of pegylated liposomal doxorubicin of 20 mg/m² on day 1, every 3 weeks. The pegylated liposomal doxorubicin dose was increased by 20% every cycle thereafter until the maximum tolerated dose was reached. The regimen selected for use in the phase II study was pegylated liposomal doxorubicin, 24 mg/m² on day 1, plus gemcitabine, 800 mg/m² on days 1 and 8, every 21 days. Results indicate that this regimen was both effective (overall response rate of 33.3%) and well tolerated.

The subsequent phase II study was conducted to evaluate the efficacy and safety of pegylated liposomal doxorubicin in combination with gemcitabine as a first-line treatment for MBC [28]. Twenty-seven of the 49 patients (55%) enrolled had undergone prior adjuvant chemotherapy; 19 of those patients had received prior anthracycline regimens. An overall response rate of 52% was observed: three complete responses and 21 partial responses, of which, two and nine responses, respectively, were in patients with previous anthracycline exposure. The median time to progression was 4.5 months and median overall survival was 10.3 months. Although the most common grade 3 or 4 toxicities were hematologic in nature, few neutropenic complications occurred during the study. The most common grade 3 or 4 nonhematologic toxicities were nausea and vomiting (10.2%), fatigue (24.5%), stomatitis (8.2%), and PPE/HFS (6.1%). Alopecia (requiring a wig) occurred in only 2/46 patients. One patient experienced a transient 21% decrease in LVEF from baseline after a cumulative pegylated liposomal doxorubicin dose of approximately 236 mg/m². That patient had predisposing risk factors (>65 years of age, prior radiation to the left chest wall, history of idiopathic pulmonary fibrosis). She was taken off the study, and her cardiac function recovered within 2 months. Another patient had a decrease in LVEF from 69.8% to 55% but remained asymptomatic with no further decline in ejection fraction while on study. Neither of those patients had clinical evidence of CHF. Based on these results, pegylated liposomal doxorubicin in combination with gemcitabine represents a viable therapeutic option for patients with MBC.

Based on the evidence discussed, combinations of pegylated liposomal doxorubicin with several other chemotherapeutic agents are effective and tolerable in patients with MBC. More importantly, combinations containing pegylated liposomal doxorubicin are effective in patients with prior anthracycline exposure. This is particularly relevant, since many patients receive conventional doxorubicin in the adjuvant setting.

	ANTHRACYCLINES PLUS TRASTUZUMAB: TOO CARDIOTOXIC?

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
Slamon and colleagues investigated the use of conventional anthracyclines as part of a combined treatment regimen with trastuzumab in women with MBC that overexpresses the human epidermal growth factor receptor (HER-2) [7]. In that study, a total of 469 patients were randomly assigned to standard treatment (i.e., anthracycline/ cyclophosphamide or paclitaxel therapy), with or without the addition of trastuzumab. Although the addition of trastuzumab was associated with a longer time to progression (7.4 months versus 4.6 months for standard chemotherapy, p < 0.001) and longer overall survival (25.1 months versus 20.3 months, p = 0.046), the high rate of cardiotoxicity in anthracycline-treated patients (27%) may preclude the use of this combination regimen. It is possible that the use of liposomal anthracycline formulations in combination with trastuzumab may reduce the incidence of cardiotoxicity, however, further study is required. This concept is discussed in more detail elsewhere in this supplement [29, 30].

	ROUNDTABLE DISCUSSION

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
Because patients treated with pegylated liposomal doxorubicin may experience dose- and schedule-dependent adverse events, such as stomatitis and PPE/HFS, respectively, our roundtable of experts briefly discussed how they are administering pegylated liposomal doxorubicin in their individual clinical practices. While pegylated liposomal doxorubicin at a dose of 50 mg/m² every 4 weeks has demonstrated similar efficacy to conventional doxorubicin [20], some participants suggested that they empirically reduce the dose of pegylated liposomal doxorubicin. Several participants said they would likely give patients pegylated liposomal doxorubicin at doses of 40 mg/m² every 4 weeks to minimize toxicities.

Results of preliminary studies in patients with MBC suggest that alternative dosing regimens may improve the tolerability of pegylated liposomal doxorubicin without compromising its antitumor activity [31]. A retrospective analysis was performed to test the hypothesis that toxicities can be decreased by administering lower doses of pegylated liposomal doxorubicin at less frequent intervals and to evaluate the efficacy of this regimen [31]. The rationale for this analysis was based on anecdotal experience that a dosage of 40 mg/m² every 4 weeks was well tolerated. The results of this retrospective analysis, as well as other analyses in patients with ovarian cancer [32, 33], suggest that pegylated liposomal doxorubicin at a dose of 40-45 mg/m² every 4 weeks deserves prospective study in patients with MBC.

	CONCLUSIONS

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
Although conventional anthracyclines are still among the most active agents available for the treatment of breast cancer, their clinical use can be substantially limited by their acute and chronic toxicity profiles, particularly myelosuppression, acute nausea and vomiting, alopecia, and cardiotoxicity. Several liposomal anthracycline formulations have been developed to improve the therapeutic index of conventional anthracyclines. These liposomal formulations maintain the efficacy of conventional doxorubicin while reducing many of the toxicities commonly associated with these agents, including cardiotoxicity.

Pegylated liposomal doxorubicin is the most extensively studied of the liposomal anthracyclines in the treatment of patients with MBC. Pegylated liposomal doxorubicin has demonstrated similar efficacy and a better safety profile than conventional doxorubicin, including significantly less cardiotoxicity, as well as less myelosuppression, nausea and vomiting, and alopecia. Pegylated liposomal doxorubicin has shown activity as both a single agent and in combination with cyclophosphamide, paclitaxel, docetaxel, and gemcitabine, with response rates ranging from 33%-75%. More importantly, pegylated liposomal doxorubicin is effective and well tolerated in patients with prior conventional doxorubicin use.

In conclusion, several clinical trials support the use of liposomal anthracyclines in patients with MBC, particularly pegylated liposomal doxorubicin. These agents exhibit comparable efficacy with conventional anthracyclines, with better safety profiles. There is growing evidence supporting the use of pegylated liposomal doxorubicin as first-line treatment for patients with MBC, owing to its antitumor activity in both anthracycline-naïve patients and in patients with previous anthracycline exposure. There is also the potential for administration of pegylated liposomal doxorubicin in combination with trastuzumab in patients with HER-2-positive disease.

	FOOTNOTES

Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 
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Top Learning Objectives Abstract Introduction Liposomal Anthracyclines Pegylated Liposomal Doxorubicin... Anthracyclines Plus Trastuzumab:... Roundtable Discussion Conclusions References

 

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