Use of paclitaxel carried in lipid core nanoparticles in patients with late-stage solid cancers with bone metastases: Lack of toxicity and therapeutic benefits

Vital, Carolina Graziani; Maranhão, Raul Cavalcante; Freitas, Fatima R.; Eyll, Brigitte M. Van; Graziani, Silvia Regina

doi:10.1016/j.jbo.2022.100431

Cited by 4 publications

(7 citation statements)

References 60 publications

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“…The pharmacokinetic studies of LDE-paclitaxel in humans confirmed that dissociation of the drug from the nanoparticle vehicle does not occur in the bloodstream and showed that the residence time of the formulation is markedly longer than that of paclitaxel-Cremophor L, which per se is a consistent pharmacological advantage over the commercial formulation [12,13]. LDE-paclitaxel had no observable laboratorial or clinical toxicity used as 3 rd or later lines of patients with ovarian adenocarcinoma [16] and in end-of-life patients with metastatic cancers [17], as administered as intravenous infusions at 175 mg/ m 2 body surface dose every 3 weeks. Uninterrupted treatments up to one year were performed without occurrence of cumulative toxicity [16,17].…”

Section: Introductionmentioning

confidence: 74%

“…To increase the lipophilicity of paclitaxel and thereby to improve the yield of association to LDE and stability of LDEpaclitaxel, we synthesized a paclitaxel derivative, paclitaxel oleate, as previously described [16,17]. The LDE-paclitaxel formulation was prepared from a lipid mixture composed of 135 mg cholesteryl oleate, 333 mg egg phosphatidylcholine, 132 mg Miglyol 812 N, 6 mg cholesterol and 60 mg of paclitaxel and the aqueous phase comprised 100 mg of polysorbate 80 and 10 ml tris-HCl buffer, pH 8.05.…”

Section: Preparation Of Paclitaxel Oleate Associated With Ldementioning

confidence: 99%

“…LDE-paclitaxel had no observable laboratorial or clinical toxicity used as 3 rd or later lines of patients with ovarian adenocarcinoma [16] and in end-of-life patients with metastatic cancers [17], as administered as intravenous infusions at 175 mg/ m 2 body surface dose every 3 weeks. Uninterrupted treatments up to one year were performed without occurrence of cumulative toxicity [16,17].…”

Section: Introductionmentioning

confidence: 99%

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Use of Paclitaxel Associated to Lipid Core Nanoparticles (LDE) in the Second or Third Line Treatment of Advanced Pancreatic Adenocarcinoma

2023

J Oncol Res Ther

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Background: Previously, we showed that paclitaxel carried in non-protein Lipid Core Nanoparticles (LDE) resembling the lipid structure of LDL has remarkably reduced toxicity in patients with advanced solid cancers, as used in 3 rd line chemotherapy or further. The aim was to test LDE-paclitaxel treatment in progressive, advanced pancreatic adenocarcinoma as second or third line of therapy.Methods: This was a prospective, single-arm study enrolling patients that had been previously submitted to at least one standard chemotherapy scheme. LDE-paclitaxel was administered at weekly infusion of 85mg/m² B.W. dose, with two-week intervals between the 7 th and the next dose.Results: Nine consecutive patients were studied. Maximum 5 cycles were performed before disease progression or death. In none of the patients treatment was discontinued or dose was reduced for drug toxicity. LDE-paclitaxel presented only CTCAE grade 1 and 2 toxicities, anemia and neuropathy being most frequent, with no grade 3 or 4 toxicities. Patient survival after initiation of LDE-paclitaxel use was 4.7 months with no decline in the assessed quality of life indices while they were being treated. Total overall survival was 20.14 months. Conclusion:LDE-paclitaxel treatment in patients with advanced pancreatic adenocarcinoma at 2 nd or 3 rd line setting showed remarkably low toxicity and tolerability and the survival data seem satisfactory in view of the previous studies from the literature. Thus, the results pave the way for future clinical trials on LDE-paclitaxel and encourage testing this formulation in 1 st line therapy schemes in pancreatic adenocarcinoma.

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Section: Introductionmentioning

confidence: 74%

Section: Preparation Of Paclitaxel Oleate Associated With Ldementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of Paclitaxel Associated to Lipid Core Nanoparticles (LDE) in the Second or Third Line Treatment of Advanced Pancreatic Adenocarcinoma

2023

J Oncol Res Ther

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“…Nanotechnologies ICD inducer ClinicalTrials.gov Phase Reference NBTXR3 RT NCT02379845 Phase II/III [197] PTX-lipid core nanoparticles PTX -Phase II [ 198,199] Anti-EGFR-IL-dox Dox NCT02833766 Phase II [200] CRLX101 RT NCT02010567…”

Section: T Ecm -Ns Reduce Ros In Tumor Tissuementioning

confidence: 99%

Promotion of ICD via Nanotechnology

Qin

Zhang

et al. 2023

Macromolecular Bioscience

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Immunotherapy represents the most promising treatment strategy for cancer, but suffers from compromised therapeutic efficiency due to low immune activity of tumor cells and an immunosuppressive microenvironment, which significantly hampers the clinical translations of this treatment strategy. To promote immunotherapy with desired therapeutic efficiency, immunogenic cell death (ICD), a particular type of death capable of reshaping body's antitumor immune activity, has drawn considerable attention due to the potential to stimulate a potent immune response. Still, the potential of ICD effect remains unsatisfactory because of the intricate tumor microenvironment and multiple drawbacks of the used inducing agents. ICD has been thoroughly reviewed so far with a general classification of ICD as a kind of immunotherapy strategy and repeated discussion of the related mechanism. However, there are no published reviews, to the authors’ knowledge, providing a systematic summarization on the enhancement of ICD via nanotechnology. For this purpose, this review first discusses the four stages of ICD according to the development mechanisms, followed by a comprehensive description on the use of nanotechnology to enhance ICD in the corresponding four stages. The challenges of ICD inducers and possible solutions are finally summarized for future ICD‐based enhanced immunotherapy.

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“…[5] Once bone metastasis occurs, patients often experience pathological fractures, bone pain, or other complications. [6,7] The 5-year survival rate of patients with bone metastases is remarkably lower than that of patients without bone metastases (3% vs 56%). [8] To date, only 3 nomograms have been targeted for bone metastasis in PCa.…”

Section: Introductionmentioning

confidence: 99%

Establishment and assessment of a nomogram for predicting prognosis in bone-metastatic prostate cancer

Liu,

Wang,

et al. 2023

Medicine

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Objective: For the purposes of patients’ consultation, condition assessments, and guidance for clinicians’ choices, we developed a prognostic predictive model to evaluate the 1-, 3-, and 5-year overall survival (OS) rates of bone-metastatic prostate cancer (PCa) patients. Methods: We gathered data from 5522 patients with bone metastatic PCa registered in the Surveillance, Epidemiology, and End Results (SEER) database to develop a nomogram. A total of 359 bone metastatic PCas were collected from 2 hospitals to validate the nomogram and assess its discriminatory ability. In addition, we plotted the actual survival against the predicted risk to assess the calibration accuracy. Moreover, we designed a web calculator to quickly obtain accurate survival probability outcomes. Results: Univariate and multivariate Cox hazard regression analyses suggested that age, marital status, prostate-specific antigen (PSA) level, Gleason score, clinical T stage, N stage, surgery, and chemotherapy were closely associated with OS rates. The calibration charts of the training and validation groups showed a high accuracy and reliability. The decision curve analysis (DCA) suggested a favorable clinical net benefit. Conclusion: Based on demography and clinical pathology, we developed a reliable nomogram to help clinicians more accurately predict the 1-, 3-, and 5-year OS rates of patients with bone metastatic PCa to guide evaluation and treatment.

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Use of paclitaxel carried in lipid core nanoparticles in patients with late-stage solid cancers with bone metastases: Lack of toxicity and therapeutic benefits

Cited by 4 publications

References 60 publications

Use of Paclitaxel Associated to Lipid Core Nanoparticles (LDE) in the Second or Third Line Treatment of Advanced Pancreatic Adenocarcinoma

Use of Paclitaxel Associated to Lipid Core Nanoparticles (LDE) in the Second or Third Line Treatment of Advanced Pancreatic Adenocarcinoma

Promotion of ICD via Nanotechnology

Establishment and assessment of a nomogram for predicting prognosis in bone-metastatic prostate cancer

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