Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis (original) (raw)
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Cancer Chemotherapy and Pharmacology, 2010
Purpose Anthracyclines and fluoropyrimidines are very active in breast cancer, while liposomal doxorubicin has low cardiotoxicity. We conducted a dose-finding study of the combination of liposomal doxorubicin and capecitabine in patients with pretreated metastatic breast cancer. Patients and methods Patients received liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2 bid (level 0) or 1,000 mg/m2 bid (level 1) on days 1–14 of each 21-day cycle to establish the maximum tolerated dose (MTD) and cardiac safety. Results Nine patients were enrolled and a total of 52 courses were delivered (median 6 cycles per patient [range 4–7]). Grade 4 neutropenia occurred in 15% of cycles, with one episode of febrile neutropenia; most nonhematological toxicities were mild or moderate. No formal MTD was established, and the study was closed because two cardiac events were observed at dose level 1 and another at dose level 0 in patients pretreated with epirubicin ≥ 560 mg/m2. Conclusions The recommended dose for phase II studies is liposomal doxorubicin 60 mg/m2 on day 1 plus capecitabine 825 mg/m2/bid on days 1–14 of each 21-day cycle. Despite the lower cardiotoxicity of liposomal doxorubicin, the risk of cardiac damage persists in anthracycline-pretreated individuals and mandates close cardiac monitoring and careful evaluation of the overall cumulative dose.
Liposomal Anthracyclines in Metastatic Breast Cancer: Clinical Update
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.
Annals of Oncology, 2004
Background: This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX™ [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC). Patients and methods: Women (n = 509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m 2 (every 4 weeks) or doxorubicin 60 mg/m 2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose. Results: PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR) = 1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR = 3.16; 95%CI 1.58-6.31; P <0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR = 0.94; 95%CI 0.74-1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin. Conclusions: In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.
Cancer Gene Therapy, 2017
Despite benefits of systemic chemotherapy in breast cancer treatment, several patients with early-stage breast cancer will develop metastatic breast cancer (MBC). Doxorubicin is among the most active agents against MBC. However, the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product claimed to achieve these two objectives because of its different pharmacokinetic profile. The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials. A literature search in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical systems, 'breast cancer' and 'doxorubicin'. Articles were evaluated according to the inclusion criteria. Reported hematological and non-hematological side effects were categorized. Out of 718 articles that were initially identified, 8 were in accordance with the inclusion criteria. We found that the most important side effects of PLD were skin toxicity and mucositis, but the proportion of patients who showed grade III and IV of these side effects was relatively low. On the other hand, the occurrence of cardiotoxicity, the most important problem with doxorubicin, was considerably reduced in patients treated with PLD. Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines, it has also new side effects. However, it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC, especially in those with risk factors for cardiac diseases.
Role of liposomal anthracyclines in breast cancer
Annals of Oncology, 2007
Anthracyclines are among the most effective drugs for patients with breast cancer. Their use, however, has been limited by associated toxic effects, 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 two liposomal formulations available for treatment of advanced disease: a not pegylated liposomal doxorubicin and a pegylated liposomal doxorubicin. This review will focus on both liposomal formulations of doxorubicin which are approved in Europe and Canada for use in patients with metastatic breast cancer.