Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts

Rakowski, J.A.; Ahmad, Sarfraz; Holloway, Robert W.

doi:10.1586/era.11.187

Cited by 12 publications

(8 citation statements)

References 49 publications

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“…In this context, we propose that our findings may be relevant in the treatment of cancers such as breast and ovarian cancers, particularly in older women, because the consumption of a calcium‐rich diet or a dietary supplement that counteracts osteoporosis (Turck ) could alter the efficacy of doxorubicin, a commonly used chemotherapeutic (Rakowski et al . ; Lao et al . ).…”

Section: Discussionmentioning

confidence: 99%

Calcium modulation of doxorubicin cytotoxicity in yeast and human cells

et al. 2016

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Doxorubicin is a widely used chemotherapeutic agent, but its utility is limited by cellular resistance and off‐target effects. To understand the molecular mechanisms regulating chemotherapeutic responses to doxorubicin, we previously carried out a genomewide search of doxorubicin‐resistance genes in Schizosaccharomyces pombe fission yeast and showed that these genes are organized into networks that counteract doxorubicin cytotoxicity. Here, we describe the identification of a subgroup of doxorubicin‐resistance genes that, when disrupted, leads to reduced tolerance to exogenous calcium. Unexpectedly, we observed a suppressive effect of calcium on doxorubicin cytotoxicity, where concurrent calcium and doxorubicin treatment resulted in significantly higher cell survival compared with cells treated with doxorubicin alone. Conversely, inhibitors of voltage‐gated calcium channels enhanced doxorubicin cytotoxicity in the mutants. Consistent with these observations in fission yeast, calcium also suppressed doxorubicin cytotoxicity in human breast cancer cells. Further epistasis analyses in yeast showed that this suppression of doxorubicin toxicity by calcium was synergistically dependent on Rav1 and Vph2, two regulators of vacuolar‐ATPase assembly; this suggests potential modulation of the calcium–doxorubicin interaction by fluctuating proton concentrations within the cellular environment. Thus, the modulatory effects of drugs or diet on calcium concentrations should be considered in doxorubicin treatment regimes.

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Section: Discussionmentioning

confidence: 99%

Calcium modulation of doxorubicin cytotoxicity in yeast and human cells

et al. 2016

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“…For example, PEGylated-liposomal doxorubicin (Doxil) was characterized by a very long circulating half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues compared with conventional liposomal doxorubicin or free doxorubicin [110,111]. Numerous liposomal drug formulations containing chemotherapeutic agents, antisense-oligodeoxynucleotides, siRNA, deoxyribonucleic acid (DNA), or radioactive particles that can target multiple signaling pathways are in various stages of development [71,92,112].…”

Section: Use Of Nanotechnology To Develop Mtismentioning

confidence: 99%

Use of Nanotechnology to Develop Multi-Drug Inhibitors for Cancer Therapy

Gowda¹,

Jones

Banerjee³

et al. 2013

J Nanomed Nanotechnol

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Therapeutic agents that inhibit a single target often cannot combat a multifactorial disease such as cancer. Thus, multi-target inhibitors (MTIs) are needed to circumvent complications such as the development of resistance. There are two predominant types of MTIs, (a) single drug inhibitor (SDIs) that affect multiple pathways simultaneously, and (b) combinatorial agents or multi-drug inhibitors (MDIs) that inhibit multiple pathways. Single agent multi-target kinase inhibitors are amongst the most prominent class of compounds belonging to the former, whereas the latter includes many different classes of combinatorial agents that have been used to achieve synergistic efficacy against cancer. Safe delivery and accumulation at the tumor site is of paramount importance for MTIs because inhibition of multiple key signaling pathways has the potential to lead to systemic toxicity. For this reason, the development of drug delivery mechanisms using nanotechnology is preferable in order to ensure that the MDIs accumulate in the tumor vasculature, thereby increasing efficacy and minimizing off-target and systemic side effects. This review will discuss how nanotechnology can be used for the development of MTIs for cancer therapy and also it concludes with a discussion of the future of nanoparticle-based MTIs as well as the continuing obstacles being faced during the development of these unique agents.’

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“…In addition, it was suggested that PLD had a more favorable toxicity profile than CϩP [7], but these findings were not always corroborated in other clinical trials [9,11]. There is a need to clarify the efficacy and toxicity profiles of CϩPLD compared with CϩP in order to facilitate therapeutic decision making and optimize patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Recent clinical trials suggest that combination therapy consisting of carboplatin with PLD (CϩPLD) may have similar or better rates of progression-free survival (PFS) and similar overall survival (OS) when compared with CϩP, the current first-line regimen [7][8][9][10]. In addition, it was suggested that PLD had a more favorable toxicity profile than CϩP [7], but these findings were not always corroborated in other clinical trials [9,11]. There is a need to clarify the efficacy and toxicity profiles of CϩPLD compared with CϩP in order to facilitate therapeutic decision making and optimize patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

et al. 2013

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Background. Recent studies suggest that carboplatin with pegylated liposomal doxorubicin (CϩPLD) is as efficacious as carboplatin with paclitaxel (CϩP) and possibly is more tolerable for ovarian cancer therapy. Pegylated liposomal doxorubicin(PLD)mayalsobeefficaciousandtolerableasmonotherapyin recurrent or platinum-resistant disease. We performed a metaanalysis of randomized trials in order to elucidate the role of PLD in ovarian cancer. Methods. We searched PubMed, Scopus, and ISI Web of Knowledge for studies comparing CϩPLD with CϩP and comparing PLD with another monotherapy. Summary hazard ratios (HRs) and relative risks with their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effects model. Results. Three trials were included in the doublet regimen analysis, and five trials were included in the monotherapy regimen analysis. CϩPLD provided superior progression-free survival (PFS) (HR, 0.87; 95% CI, 0.78 -0.96) and similar overall survival (OS; HR, 0.95; 95% CI, 0.84 -1.07) compared with CϩP. There was no evidence of improved tolerability: CϩPLD had more gastrointestinal toxicity, anemia, thrombocytopenia, cutaneous toxicity, and mucositis/stomatitis, although there was less neutropenia, neuropathy, and alopecia. PLD monotherapy had similar PFS (HR, 0.99; 95% CI, 0.89 -1.11) and OS (HR, 0.99; 95% CI, 0.88 -1.11) to other monotherapies, but it was more tolerable. There was less neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity, although cutaneous toxicity was increased. Conclusion. CϩPLD had better PFS and similar OS compared with CϩP and had a very different toxicity profile. Therapy selection could be based on patient risks for side effects. PLD is as efficacious as other monotherapies and is more tolerable. The Oncologist 2013;18:1022-1031 Implications for Practice: Carboplatin with paclitaxel (CϩP) has been the standard first-line chemotherapy regimen for ovarian cancer patients; however, two large randomized trials of carboplatin and pegylated liposomal doxorubicin (CϩPLD) versus CϩP suggest that CϩPLD is as efficacious as CϩP and possibly is more tolerable. The results of our analysis showed that CϩPLD has better progression-free survival than CϩP and similar overall survival; however, we did not find CϩPLD to be more tolerable than CϩP. The toxicity profiles were very different, and therapy selection could reasonably be based on individual patient risks of side effects. Pegylated liposomal doxorubicin (PLD) is also a treatment option for recurrent or platinum-resistant ovarian cancer, but there is no clear distinction among any of the monotherapy options in this setting. The results of our analysis showed that PLD is as efficacious as other monotherapies and is more tolerable. Consequently, it may be the preferred agent in the palliative setting. INTRODUCTIONOvarian cancer is the leading cause of death from gynecologic malignancies in the United States [1]. Standard first-line treatment includes surgical debulking and platinum-based chemotherapy, us...

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Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts

Cited by 12 publications

References 49 publications

Calcium modulation of doxorubicin cytotoxicity in yeast and human cells

Calcium modulation of doxorubicin cytotoxicity in yeast and human cells

Use of Nanotechnology to Develop Multi-Drug Inhibitors for Cancer Therapy

The Role of Pegylated Liposomal Doxorubicin in Ovarian Cancer: A Meta-Analysis of Randomized Clinical Trials

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