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Clinical Genitourinary Cancer Dec 2020The addition of docetaxel and abiraterone to androgen deprivation therapy (ADT) heralded a new era in the first-line treatment of metastatic castration-sensitive... (Review)
Review
The addition of docetaxel and abiraterone to androgen deprivation therapy (ADT) heralded a new era in the first-line treatment of metastatic castration-sensitive prostate cancer (mCSPC). Following the success of these combination regimens, 3 new trials presented data on using enzalutamide or apalutamide in men with mCSPC, which showed similar success. These seminal trials collectively established the addition of docetaxel, enzalutamide, apalutamide, or abiraterone to ADT as standards in the upfront treatment of mCSPC. Notably, a subset of patients in these more recent trials were treated with a combination of docetaxel, ADT, and androgen receptor signaling inhibitors or maintenance androgen receptor signaling inhibitors after docetaxel and ADT that provided an initial glimpse into the efficacy of these triplet or maintenance strategies. We discuss the implications of these recent findings and place them in context of the current mCSPC treatment landscape.
Topics: Androgen Antagonists; Androgens; Castration; Docetaxel; Humans; Male; Prostatic Neoplasms; Receptors, Androgen; Treatment Outcome
PubMed: 32631766
DOI: 10.1016/j.clgc.2020.05.003 -
Cancer Chemotherapy and Pharmacology Feb 2022Large interindividual variability in the pharmacokinetic properties of docetaxel has been reported, with the clearance of docetaxel varying nearly six fold, in which... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Large interindividual variability in the pharmacokinetic properties of docetaxel has been reported, with the clearance of docetaxel varying nearly six fold, in which pharmacogenetics of docetaxel may play an essential role in addition to physiological factors. The association between the gene polymorphism and risk of adverse clinical effects in docetaxel treated patients has been examined in several studies, but their conclusions are, to some extent, controversial. To clarify the role of gene polymorphism in the clinical outcomes of docetaxel treatment, a meta-analysis was performed in the present study.
METHODS
Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of gene polymorphisms of CYP3A4, CYP3A5 and ABCB1. Four studies with 485 subjects were included in this study. Fixed or random-effects model was chosen according to heterogeneity to conduct the meta-analysis. Publication bias was evaluated by fail-safe numbers.
RESULTS
Significant association was identified between the ABCB1 C3435T (rs1045642) polymorphism and risk of short-term recurrent hematological toxicity (TT vs. CC + TC OR = 2.91, 95% CI 1.30-6.52, P = 0.009; TT vs. CC OR = 4.23, 95% CI 1.69-10.57 P = 0.002). The association of the ABCB1 G2677T/A (rs2032582) polymorphism with risk of fluid retention was statistically significant (T(A)/T(A) vs. GG + GT(A) OR = 2.08, 95% CI 1.16-3.73, P = 0.01). No statistically significant association between the CYP3A5 A6986G (rs776746) polymorphism and adverse effects was observed in this study. Due to the limitations of included literature, we did not conduct meta-analysis on CYP3A4 gene polymorphism and adverse effects.
CONCLUSION
An association between the ABCB1 C3435T (rs1045642), ABCB1 G2677T/A (rs2032582) polymorphism and risk of adverse effects of docetaxel was found by our meta-analysis. Namely, the TT homozygotes of the ABCB1 C3435T polymorphism may be associated with the risk of hematological toxicity. ABCB1 G2677T T(A)/T(A) genotype may be associated with the fluid retention.
TRAIL REGISTRATION
PROSPERO 2020 CRD42020203132.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antineoplastic Agents; Cytochrome P-450 CYP3A; Docetaxel; Genotype; Humans; Neoplasms; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 34988655
DOI: 10.1007/s00280-021-04374-3 -
Cancer Science Feb 2024Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance...
Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance and in the absence of effective treatment options. Consequently, it is essential to investigate the mechanisms generating docetaxel resistance and develop novel alternative therapeutic targets. RNA sequencing was undertaken on docetaxel-sensitive and docetaxel-resistant prostate cancer (PCa) cells. Subsequently, chemoresistance, cancer stemness, and lipid metabolism were investigated. To obtain insight into the precise activities and action mechanisms of NOTCH3 in docetaxel-resistant PCa, immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, cell metabolism, and animal experiments were performed. Through RNA sequencing analysis, we found that NOTCH3 expression was markedly higher in docetaxel-resistant cells relative to parental cells, and that this trend was continued in docetaxel-resistant PCa tissues. Experiments in vitro and in vivo revealed that NOTCH3 enhanced stemness, lipid metabolism, and docetaxel resistance in PCa. Mechanistically, NOTCH3 is bound to TUBB3 and activates the MAPK signaling pathway. Moreover, NOTCH3 was directly regulated by MEF2A in docetaxel-resistant cells. Notably, targeting NOTCH3 and the MEF2A/TUBB3 signaling axis was related to docetaxel chemoresistance in PCa. Overall, these results demonstrated that NOTCH3 fostered stemness, lipid metabolism, and docetaxel resistance in PCa via the TUBB3 and MAPK signaling pathways. Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.
Topics: Male; Animals; Humans; Docetaxel; Drug Resistance, Neoplasm; Cell Line, Tumor; Prostatic Neoplasms; Signal Transduction; Tubulin; Receptor, Notch3
PubMed: 38115797
DOI: 10.1111/cas.16040 -
Future Medicinal Chemistry Feb 2021Glioblastoma multiforme (GBM) is the most prevalent and aggressive form of glioma, with poor prognosis and high mortality rates. As GBM is a highly vascularized cancer,... (Review)
Review
Glioblastoma multiforme (GBM) is the most prevalent and aggressive form of glioma, with poor prognosis and high mortality rates. As GBM is a highly vascularized cancer, antiangiogenic therapies to halt or minimize the rate of tumor growth are critical to improving treatment. In this review, antiangiogenic therapies, including small-molecule drugs, nucleic acids and proteins and peptides, are discussed. The authors further explore biomaterials that have been utilized to increase the bioavailability and bioactivity of antiangiogenic factors for better antitumor responses in GBM. Finally, the authors summarize the current status of biomaterial-based targeting moieties that target endothelial cells in GBM to more efficiently deliver therapeutics to these cells and avoid off-target cell or organ side effects.
Topics: Angiogenesis Inhibitors; Biocompatible Materials; Brain Neoplasms; Combined Modality Therapy; Docetaxel; Glioblastoma; Humans; Minocycline; Nucleic Acids; Small Molecule Libraries
PubMed: 33399488
DOI: 10.4155/fmc-2020-0289 -
Journal of Oncology Pharmacy Practice :... Jul 2019This article compares gravimetry vs. high-performance liquid chromatography (HPLC) as quality control (QC) methods for paclitaxel, docetaxel and oxaliplatin...
This article compares gravimetry vs. high-performance liquid chromatography (HPLC) as quality control (QC) methods for paclitaxel, docetaxel and oxaliplatin preparations. We aimed at assessing the preparation method reliability in our hospital, evaluating compounding accuracy and estimating the influence of personnel training and standardized homogenization on compounding accuracy. Agreement, correlation, concordance, accuracy and precision between methods were evaluated for each drug. Conforming preparation percentages (CPs) at different tolerance limits (TLs) and compounding accuracy were calculated for each method and drug. Compounding accuracy was compared before and after personnel training and standardized homogenization implantation. SPSS v 20.0 and Ene v 2.0 were used. A total of 222 samples (58 docetaxel, 95 paclitaxel and 69 oxaliplatin) were analyzed. Gravimetry and HPLC are comparable methods. Overall CP was 81% for gravimetry at 10% TL and 85% for HPLC at 15% TL. Compounding accuracy is shown to be good for all methods and drugs. Homogenization optimization and personnel training make measurements more accurate for docetaxel and paclitaxel HPLC, but seem to worsen accuracy for docetaxel gravimetry. Gravimetry has shown to be a good alternative to HPLC for routine QC. Coupling with electronic methods should be considered in the future.
Topics: Antineoplastic Agents; Chromatography, High Pressure Liquid; Docetaxel; Humans; Paclitaxel; Quality Control; Reproducibility of Results
PubMed: 30895861
DOI: 10.1177/1078155219834999 -
International Journal of Nanomedicine 2021Nanocarriers, with a high drug loading content and good safety, to achieve desirable therapeutic effect are always the goals for industry and research.
PURPOSE
Nanocarriers, with a high drug loading content and good safety, to achieve desirable therapeutic effect are always the goals for industry and research.
METHODS AND RESULTS
In the present study, we developed a docetaxel loaded poly-2-oxazoline polymer micellar system which employed poly-2-butyl-2 oxazoline and poly-2-methyl-2 oxazoline as the hydrophobic chain and hydrophilic chain, respectively. This micellar system achieves a high load up to 25% against the docetaxel, and further demonstrates an IC50 as low as 40% of the commercialized docetaxel injection in vitro and a double maximum tolerated dose in MCF-7 cells in vivo.
CONCLUSION
The high drug loading content, superior safety, and considerable anti-cancer activity make this newly developed docetaxel loaded poly(2-oxazoline) micelle go further in future clinical research.
Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Docetaxel; Drug Carriers; Drug Liberation; Endocytosis; Humans; Hydrophobic and Hydrophilic Interactions; MCF-7 Cells; Male; Maximum Tolerated Dose; Mice, Inbred BALB C; Mice, Nude; Micelles; Neoplasms; Oxazoles; Particle Size; Surface-Active Agents; Tissue Distribution; Mice
PubMed: 33859475
DOI: 10.2147/IJN.S298093 -
Investigative and Clinical Urology Nov 2020To assess the efficacy and safety of docetaxel rechallenge in the salvage setting in metastatic castration-resistant prostate cancer (mCRPC) patients.
PURPOSE
To assess the efficacy and safety of docetaxel rechallenge in the salvage setting in metastatic castration-resistant prostate cancer (mCRPC) patients.
MATERIALS AND METHODS
Clinicopathologic data from patients treated with docetaxel rechallenge were collected from a single-center cancer registry. Among 227 patients who received first-line docetaxel for mCRPC between January 2011 and June 2019, 23 undergo rechallenge docetaxel after failure to androgen receptor targeting agents and/or cabazitaxel treatment. Endpoints included radiologic progression-free survival (PFS), treatment duration, and prostate-specific antigen (PSA) response and safety.
RESULTS
Overall, 30%, 44%, 13%, and 13% of patients received docetaxel rechallenge as either the third, fourth, fifth, or sixth-line therapy, respectively, at a median of 23.6 months after stopping first-line docetaxel. With first-line docetaxel and rechallenge, median treatment duration was 6.4 and 3.3 months, respectively. With docetaxel rechallenge, PSA response was 35% (95% confidence interval [CI], 15% to 54%) and median PFS was 4.5 months (95% CI, 1.9 to 7.1 months). The median OS was 24.3 months (95% CI, 4.6 to 44.0 months). There were 7 severe adverse events (grade 3 or more) including anemia (8.7%), neutropenia, thrombocytopenia, leukopenia, diarrhea, and nausea (4.3% each).
CONCLUSIONS
Docetaxel rechallenge showed meaningful anti-tumor activity with acceptable toxicity in heavily pretreated patients with mCRPC.
Topics: Aged; Antineoplastic Agents; Docetaxel; Humans; Male; Middle Aged; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome
PubMed: 32985144
DOI: 10.4111/icu.20200214 -
Scientific Reports Nov 2023Ganoderma lucidum polysaccharide is the most widely used complementary therapy in cancer. The present study aims to investigate the possible interaction between...
Ganoderma lucidum polysaccharide is the most widely used complementary therapy in cancer. The present study aims to investigate the possible interaction between Ganoderma lucidum polysaccharide and Docetaxel (a chemotherapy drug) and the first-line medication for prostate cancer treatment (Flutamide) and sensitizing the cells to these treatments. The cytotoxic effects of Ganoderma lucidum polysaccharide in combination with Docetaxel and Flutamide on prostate cancer cells were investigated by the MTT test, Hoechst staining, and flow cytometry. In addition, the expression of genes related to apoptosis, angiogenesis, Epithelial-Mesenchymal Transition pathway (EMT), and prostate cancer biomarkers by Real-Time PCR was investigated. The results demonstrated that IC50 values for Ganoderma lucidum polysaccharide (30 μM and 20 μM), Docetaxel (10 μM and 5 μM), and Flutamide (20 μM and 12 μM) with MTT were confirmed by flow cytometry in a dose and time-dependent manner. Regarding the high efficacy of Ganoderma lucidum polysaccharide in combination with Flutamide and Docetaxel, 10 μM and 5 μM Flutamide were used instead of 20 μM and 12 μM and 5 μM and 2 μM Docetaxel was used instead of 10 μM and 5 μM in PC3 and LNCap, respectively. Moreover, for the first time, it was shown that Ganoderma lucidum polysaccharide alone and in combination with Docetaxel and Flutamide significantly augmented apoptosis, reduced cell migration and colonization, and downregulated expression of KLK2 and EMT pathway genes in both PC3 and LNCap cell line (P < 0.01). Ganoderma lucidum polysaccharide synergistically increased the effect of Docetaxel and Flutamide and increased the sensitivity of the prostate cancer cell lines to these drugs. Therefore, it may provide a new therapeutic strategy against prostate cancer.
Topics: Male; Humans; Docetaxel; Reishi; Prostate; Flutamide; Prostatic Neoplasms; Cell Line, Tumor; Polysaccharides
PubMed: 37919464
DOI: 10.1038/s41598-023-46118-8 -
Current Drug Delivery 2020Since the discovery of liposomes, these vesicular carriers have attracted the researchers from all the vistas of the biomedical domain to explore and harness the... (Review)
Review
Since the discovery of liposomes, these vesicular carriers have attracted the researchers from all the vistas of the biomedical domain to explore and harness the potential benefits. Many novel drug delivery-based products have been approved by the United States Food and Drug Administration (USFDA) and other federal agencies of the globe, out of which the major share is of the liposomes and related carriers. Taking cognizance of it, the US-FDA has recently come up with 'Guidance for Industry on Liposome Drug Products'. In cancer management, chemotherapy is the most frequently employed approach which is still not devoid of untoward challenges and side effects. In chemotherapy, the taxanes, esp. Docetaxel shares a huge percentage in the prescription pattern. Also, the first marketed liposomal product was encasing one drug of this category. Henceforth, the present review will highlight the advances in the delivery of taxanes, in particular docetaxel, with an emphasis on the need, success and pharmacoeconomic aspects of such vesicular-carrier mediated docetaxel delivery.
Topics: Docetaxel; Drug Carriers; Drug Delivery Systems; Humans; Liposomes; Neoplasms; Taxoids
PubMed: 32576129
DOI: 10.2174/1567201817666200623121633 -
Biomedicine & Pharmacotherapy =... Sep 2021Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis and migration of cancer cells to neighboring cells and tissues. Morphologically,... (Review)
Review
Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis and migration of cancer cells to neighboring cells and tissues. Morphologically, epithelial cells are transformed to mesenchymal cells, and at molecular level, E-cadherin undergoes down-regulation, while an increase occurs in N-cadherin and vimentin levels. Increasing evidence demonstrates role of EMT in mediating drug resistance of cancer cells. On the other hand, paclitaxel (PTX) and docetaxel (DTX) are two chemotherapeutic agents belonging to taxene family, capable of inducing cell cycle arrest in cancer cells via preventing microtubule depolymerization. Aggressive behavior of cancer cells resulted from EMT-mediated metastasis can lead to PTX and DTX resistance. Upstream mediators of EMT such as ZEB1/2, TGF-β, microRNAs, and so on are involved in regulating response of cancer cells to PTX and DTX. Tumor-suppressing factors inhibit EMT to promote PTX and DTX sensitivity of cancer cells. Furthermore, three different strategies including using anti-tumor compounds, gene therapy and delivery systems have been developed for suppressing EMT, and enhancing cytotoxicity of PTX and DTX against cancer cells that are mechanistically discussed in the current review.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Docetaxel; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Humans; Neoplasms; Paclitaxel
PubMed: 34175815
DOI: 10.1016/j.biopha.2021.111824