nab-Paclitaxel for the treatment of breast cancer: an update across treatment settings

Brufsky, Adam

doi:10.1186/s40164-017-0066-5

Cited by 25 publications

(17 citation statements)

References 60 publications

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“…Nano-sized drug carrier systems can also prolong the circulation time of anti-cancer drugs, protect them from degradation, and sustain therapeutic drug concentrations due to prolonged/ controlled drug release. In addition, nanoparticles can be used 60 to administer poorly soluble agents, as demonstrated for Nab-paclitaxel, an HSA nanoparticlebased paclitaxel preparation approved for the treatment of different forms of cancer [Brufsky, 2017;Mir et al, 2017;Ricciardi et al, 2018;Rodallec et al, 2018;Tan et al, 2018;Zhao et al, 2018].…”

Section: Introduction 45mentioning

confidence: 99%

Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity

Pieper

Onafuye

Mulac

et al. 2018

Preprint

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20Nanoparticles are under investigation as carrier systems for anti-cancer drugs. They have been shown to accumulate in cancer tissues through the enhanced permeability and retention (EPR) effect, to reduce toxicity to non-target tissues, and to protect drugs from preliminary inactivation. However, nanoparticle preparations are not commonly compared for their anticancer effects at the cellular level. Here, we prepared doxorubicin-loaded nanoparticles based 25 on poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) by solvent displacement and emulsion diffusion approaches. The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement resulted in the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH7 reaching 53 µg doxorubicin/mg nanoparticle. 30In addition, these PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anti-cancer effects. In conclusion, 35 doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anti-cancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anti-cancer efficacy. The design of drug-loaded nanoparticles with optimised anti-cancer activity at the cellular level is an important step in the development of improved 40 nanoparticle preparations for anti-cancer therapy.

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Section: Introduction 45mentioning

confidence: 99%

Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity

Pieper

Onafuye

Mulac

et al. 2018

Preprint

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“…HSA nanoparticles may be internalised upon interaction with cellular albumin receptors [30–31]. Notably, nab-paclitaxel, an HSA nanoparticle-based preparation of paclitaxel (another ABCB1 substrate [21]), which is approved for the treatment of different forms of cancer [32], had previously been shown not to avoid ABCB1-mediated drug efflux [33]. However, nab-paclitaxel is not produced by the use of cross-linkers, and the interaction of paclitaxel with albumin may differ from that of doxorubicin.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin-loaded human serum albumin nanoparticles overcome transporter-mediated drug resistance in drug-adapted cancer cells

Onafuye¹,

Pieper²,

Mulac³

et al. 2019

Beilstein J. Nanotechnol.

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Resistance to systemic drug therapy is a major reason for the failure of anticancer therapies. Here, we tested doxorubicin-loaded human serum albumin (HSA) nanoparticles in the neuroblastoma cell line UKF-NB-3 and its ABCB1-expressing sublines adapted to vincristine (UKF-NB-3rVCR1) and doxorubicin (UKF-NB-3rDOX20). Doxorubicin-loaded nanoparticles displayed increased anticancer activity in UKF-NB-3rVCR1 and UKF-NB-3rDOX20 cells relative to doxorubicin solution, but not in UKF-NB-3 cells. UKF-NB-3rVCR1 cells were re-sensitised by nanoparticle-encapsulated doxorubicin to the level of UKF-NB-3 cells. UKF-NB-3rDOX20 cells displayed a more pronounced resistance phenotype than UKF-NB-3rVCR1 cells and were not re-sensitised by doxorubicin-loaded nanoparticles to the level of parental cells. ABCB1 inhibition using zosuquidar resulted in similar effects like nanoparticle incorporation, indicating that doxorubicin-loaded nanoparticles successfully circumvent ABCB1-mediated drug efflux. The limited re-sensitisation of UKF-NB-3rDOX20 cells to doxorubicin by circumvention of ABCB1-mediated efflux is probably due to the presence of multiple doxorubicin resistance mechanisms. So far, ABCB1 inhibitors have failed in clinical trials probably because systemic ABCB1 inhibition results in a modified body distribution of its many substrates including drugs, xenobiotics, and other molecules. HSA nanoparticles may provide an alternative, more specific way to overcome transporter-mediated resistance.

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“…27 Additionally, recent clinical trials with nab-P demonstrating high pathologic complete response rates in the neoadjuvant setting in early stage breast cancer, particularly in the difficult-to-treat subgroup of TNBC, are encouraging. 28,29 Considering the safety of nab-P treatment for patients with MBC, the NIS NABUCCO observed a favorable riskebenefit profile in the real-world setting. The safety profile of nab-P was consistent with safety data published in past clinical trials, including the registrational phase III trial.…”

Section: Norbert Marschner Et Almentioning

confidence: 99%

Final Effectiveness and Safety Results of NABUCCO: Real-World Data From a Noninterventional, Prospective, Multicenter Study in 697 Patients With Metastatic Breast Cancer Treated With nab-Paclitaxel

Marschner¹,

Salat²,

Söling³

et al. 2018

Clinical Breast Cancer

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The noninterventional study NABUCCO evaluated effectiveness and safety of nab-paclitaxel in 697 patients with metastatic breast cancer (MBC) treated in routine care. The results confirm the clinical trial outcomes, the favorable benefiterisk profile of nab-paclitaxel, and the sustained global quality of life in patients with MBC in a real-world setting. Background: One of the most effective chemotherapies for metastatic breast cancer (MBC) is nab-paclitaxel (nab-P), which is approved for treatment of MBC after failure of first-line therapy and when anthracyclines are not indicated. Randomized clinical trials have shown high efficacy and acceptable toxicity. Real-world data of nab-P in MBC, however, are still limited. Patients and Methods: The prospective multicenter noninterventional study NABUCCO collected data on the routine treatment of patients with MBC receiving nab-P in 128 sites across Germany. The primary objective was time to progression. Secondary objectives were overall response rate, overall survival, safety, and quality of life. Results: Between April 2012 and April 2015, a total of 705 patients with MBC at 128 active sites had been enrolled. A total of 697 patients had evaluable data with a median follow-up of 17.7 months. Median time to progression was 5.9 months (95% confidence interval, 5.6-6.4), overall response rate was 37.2%, and median overall survival was 15.6 months (95% confidence interval, 14.2-17.2). The results were similar in patients aged < 65 versus ! 65 years as well as in patients who received nab-P on a weekly or a triweekly schedule. The most frequently reported grade 3/4 adverse events were leukopenia (55, 7.9%), peripheral sensory neuropathy (30, 4.3%), and infections (29, 4.2%). Patients reported no apparent treatment-related impact on global quality of life. Conclusion: The results of the NABUCCO study confirm the clinical trial outcomes and the favorable safety profile of nab-P in patients with metastatic breast cancer in a real-world setting.

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nab-Paclitaxel for the treatment of breast cancer: an update across treatment settings

Cited by 25 publications

References 60 publications

Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity

Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity

Doxorubicin-loaded human serum albumin nanoparticles overcome transporter-mediated drug resistance in drug-adapted cancer cells

Final Effectiveness and Safety Results of NABUCCO: Real-World Data From a Noninterventional, Prospective, Multicenter Study in 697 Patients With Metastatic Breast Cancer Treated With nab-Paclitaxel

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