The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials

Abstract

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.

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

“…They interact with DNA base pairs and inhibit macromolecular biosynthesis; likewise, they are related with topoisomerase II after it has broken the DNA chain, stopping DNA replication. Their most important side effect is cardiotoxicity, which considerably hinders the scope of their use [86]. There are many studies that have evaluated the efficacy of antracyclines, but the most recent is a PELICAN trial: a phase III study that noticed that both doxorrubicin and capecitabine are effective as first line therapy for metastatic BC [87].…”

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

“…Therefore, patients on DOX chemotherapy are monitored regularly to assess cardiac LVEF and chemotherapy cessation is recommended when values drop below 40% [14]. PEGylated liposomal formulations of DOX can reduce the incidence of cardiotoxicity, though they have been associated with other side effects such as skin toxicity [15]. Currently, there are no cardiotoxicity-specific treatments, neither prophylactic nor curative, and cardioprotective drugs trialled in patients to treat DOX cardiotoxicity are sparse and include standard heart failure medications such as renin angiotensin system blockers and beta blockers [12,16].…”

Soft and flexible poly(ethylene glycol) nanotubes for local drug delivery

“… 19 Doxorubicin is commonly used as part of the treatment regime for both early stage and metastatic breast cancer, but has severe toxicity issues. 20 Local drug delivery strategies represent a way to enhance the effectiveness of the drug, whilst reducing its side effects, by releasing a high concentration of the drug focally to the tumor. Local drug delivery is already in use for a range of malignancies, and drug delivery devices in development take on a range of different forms including wafers, films, nanoparticles, gels and rods (reviewed elsewhere 21 ).…”

“…We speculate that this could be due to cardiotoxicity, a well-known side effect of doxorubicin therapy. 20 , 35 Assessment of tumor weight at the end of the study showed that i.v. doxorubicin dosing reduced the average tumor mass from 549 mg ± 326 ( i.e.…”