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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 -
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 -
American Journal of Men's Health 2022Due to the COVID-19 pandemic, major congresses and many teaching opportunities as well as the usual visits from medical advisors of pharmaceutical firms have been...
Due to the COVID-19 pandemic, major congresses and many teaching opportunities as well as the usual visits from medical advisors of pharmaceutical firms have been postponed and canceled. The major trials of prostate cancer in the last 5 years in each state are shortly discussed providing a panoramic overview of the available evidence and data on prostate cancer treatment. Apalutamide, enzalutamide, and darolutamide have proven to have clinical benefits when added to androgen deprivation therapy for patients with nonmetastatic castration-resistant prostate cancer. In patients in the metastatic hormone-sensitive setting, next to docetaxel, abiraterone, enzalutamide, and apalutamide have been shown to significantly improve overall survival and progression-free survival in comparison to standard hormone therapy. In addition, docetaxel abiraterone and enzalutamide are widely used in the metastatic setting. For second-line therapy of metastasized prostate cancer patients who have received either docetaxel or abiraterone or enzalutamide, olaparib, cabazitaxel, radium, and lutetium therapy have been shown to be beneficial in selected patient groups.
Topics: Androgen Antagonists; COVID-19; Docetaxel; Hormones; Humans; Male; Pandemics; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 35950609
DOI: 10.1177/15579883221115593 -
In Vivo (Athens, Greece) 2021Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of...
BACKGROUND/AIM
Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC.
PATIENTS AND METHODS
We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival.
RESULTS
Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group.
CONCLUSION
The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Treatment Outcome
PubMed: 34697189
DOI: 10.21873/invivo.12653 -
Disease Markers 2022To compare the clinical efficacy and long-term survival between anlotinib monotherapy and anlotinib plus docetaxel in patients with lung carcinoma. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare the clinical efficacy and long-term survival between anlotinib monotherapy and anlotinib plus docetaxel in patients with lung carcinoma.
METHODS
Between October 2019 and December 2021, 84 patients with lung cancer diagnosed and treated at our hospital were enrolled and randomly allocated to the control ( = 42) and experimental ( = 42) groups. Patients in the control group only received anlotinib, whereas those in the experimental group were administered both anlotinib and docetaxel. The clinical effectiveness, long-term survival, and other associated variables of the two groups were compared.
RESULTS
There were no CR cases, 7 PR cases, 22 SD cases, and 13 PD cases in the control group. In the experimental group, there were 4 cases of CR, 20 cases of CR, 11 cases of SD, and 7 cases of PD. The overall clinical effectiveness of the experimental group was much higher than that of the control group. There were 3 cases of anemia, 5 cases of pyrexia, 6 cases of proteinuria, 9 cases of nausea and vomiting, and 4 cases of abnormal liver and renal function in the control group. ( < 0.05). In the experimental group, there were 2 cases of anemia, 3 cases of pyrexia, 1 case of proteinuria, 5 cases of nausea and vomiting, and 1 case of abnormal liver and kidney function. The incidence of adverse reactions in the experimental group was significantly lower than in the control group (64.29%) ( < 0.05). According to the two-year follow-up results, the survival rate was 19.05% in the control group and 54.76% in the experimental group, and the mortality rate was 80.95% in the control group and 45.24% in the experimental group. The experimental group had a significantly higher survival rate than the control group ( < 0.05).
CONCLUSION
Anlotinib combined with docetaxel is a safe and effective treatment for lung carcinoma to reduce the incidence of adverse reactions and improve the long-term survival rate. These benefits make it worthy of a broader clinical application. Although pharmacological treatment was applied in this study based on the mechanism, specific bioeffective markers are yet to be identified, presenting a direction for future research.
Topics: Humans; Carcinoma; Docetaxel; Fever; Lung; Lung Neoplasms; Nausea; Proteinuria; Treatment Outcome; Vomiting
PubMed: 36277984
DOI: 10.1155/2022/2483816 -
Current Oncology (Toronto, Ont.) Dec 2022In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway... (Meta-Analysis)
Meta-Analysis
Addition of New Androgen Receptor Pathway Inhibitors to Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Metanalysis.
In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway inhibitors (ARPI) have been shown to improve overall survival (OS) compared to androgen deprivation therapy (ADT). Recent data could once again radically change mHSPC treatment. PEACE-1 and ARASENS trials demonstrated a survival benefit of the addition of ARPI to docetaxel and ADT combination (triplet therapy), compared to docetaxel and ADT. With multiple options to choose from, it is crucial to identify the patients who would benefit most from triplet therapy. In this meta-analysis, we evaluated the activity of the triplet therapy versus docetaxel plus ADT in mHSPC. A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed. Five RCTs fulfilled the inclusion criteria. PEACE-1 and ARASENS studies reported disease-free survival (DFS) and OS. Post hoc analysis of three other trials evaluated the combination of ARPI, docetaxel and ADT. Globally, 2538 patients were included (1270 triplet therapy; 1268 docetaxel + ADT). Triplet therapy was associated with improved OS (hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.66-0.83, < 0.00001). A statistically significant benefit was shown in high-volume mHSPC patients (HR 0.76; 95% CI 0.59-0.97, = 0.03) and in patients with de novo metastatic disease (HR 0.73; 95% CI, 0.64-0.82, < 0.00001). The addition of ARPI to standard therapy was associated with DFS improvement (HR 0.41; 95% CI, 0.35-0.49, < 0.00001). This metanalysis shows a significant OS benefit from concomitant administration of ARPI, docetaxel and ADT in high volume and de novo mHSPC.
Topics: Humans; Male; Androgens; Docetaxel; Prostatic Neoplasms; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36547161
DOI: 10.3390/curroncol29120747 -
Lipids in Health and Disease Feb 2021The association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (DR-CRPC) is not fully understood. While it is known...
BACKGROUND
The association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (DR-CRPC) is not fully understood. While it is known that increases in select lipids correlate to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments is well characterized.
METHODS
This gap-in-knowledge was addressed using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS (LC-ESI-MS/MS) lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment Analysis (LIPEA).
RESULTS
Several lipid regulatory pathways were identified that are associated with Docetaxel resistance in prostate cancer (PCa). These included those controlling glycerophospholipid metabolism, sphingolipid signaling and ferroptosis. In total, 7460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). Alterations were also identified in the levels of phosphatidic acid (PA) and diacylglyceride (DAG), whose levels are regulated by Lipin (LPIN), a phosphatidic acid phosphatase that converts PA to DAG. Data derived from cBioPortal demonstrated a population of PCa patients expressing mutations aligning with amplification of LPIN1, LPIN2 and LPIN3 genes. Lipin amplification in these genes correlated to decreased survival in these patients. Lipin-1 mRNA expression also showed a similar trend in PCa patient data. Lipin-1, but not Lipin-2 or - 3, was detected in several prostate cancer cells, and was increased in 22RV1 and PC-3 cell lines. The increased expression of Lipin-1 in these cells correlated with the level of PA.
CONCLUSION
These data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of PCa. The data also suggest a correlation between the expression of Lipin-1 in cells and patients with regards to prostate cancer cell aggressiveness and patient survivability. Ultimately, these data may be useful for identifying markers of lethal and/or metastatic prostate cancer.
Topics: Adult; Aged; Antineoplastic Agents; Cell Line, Tumor; Docetaxel; Drug Resistance, Neoplasm; Ferroptosis; Gene Expression Regulation, Neoplastic; Humans; Lipid Metabolism; Lipidomics; Lipids; Male; Middle Aged; Neoplasm Metastasis; Nuclear Proteins; Phosphatidate Phosphatase; Prostatic Neoplasms; Signal Transduction
PubMed: 33596934
DOI: 10.1186/s12944-021-01437-5 -
Journal of Biomedical Science Feb 2022Docetaxel has been approved by USFDA as a first-line treatment for castration-resistant prostate cancer (CRPC) patients. Patients receiving androgen deprivation therapy...
Combination treatment of docetaxel with caffeic acid phenethyl ester suppresses the survival and the proliferation of docetaxel-resistant prostate cancer cells via induction of apoptosis and metabolism interference.
BACKGROUND
Docetaxel has been approved by USFDA as a first-line treatment for castration-resistant prostate cancer (CRPC) patients. Patients receiving androgen deprivation therapy along with docetaxel result in superior survival, lower serum prostate specific antigen (PSA) level, and better quality of life. However, a significant proportion of these patients ultimately develop resistance to docetaxel within months. Caffeic acid phenethyl ester (CAPE), one of the main bioactive components extracted from the propolis, has been reported to be effective for repressing the tumor growth, the migration and invasion of prostate cancer (PCa) cells, as well as the downstream signaling and stability of androgen receptor (AR). We hence determined if combination treatment of docetaxel with CAPE can suppress the proliferation and the survival of docetaxel-resistant PCa cells.
METHODS
We established docetaxel-resistant PC/DX25 and DU/DX50 CRPC cell lines from PC-3 and DU-145 human PCa cells, respectively. Proliferation assay, MTT assay, flow cytometry with Annexin V staining, Comet Assay, and nude mice xenograft model were applied to determine the effects of combination treatment on cell proliferation and survival of the docetaxel-resistant PCa cells. Micro-Western Array (MWA) and qRT-PCR were used to investigate the molecular mechanism lying underneath.
RESULTS
Combination treatment effectively suppressed the proliferation, survival and tumor growth of docetaxel-resistant PCa cells both in vitro and in nude mice. Comet assay and flow cytometry indicated that combination treatment induced apoptosis in docetaxel-resistant PCa cells. MWA and Western blotting assay revealed that combination treatment suppressed protein expression of Bcl-2, AKT2, c-Myc, apoptosis and caspase activation inhibitor (AVEN), pyruvate kinase M2 (PKM2) but increased protein expression of Bax, caspase 3, cytochrome c, glucose-6-phosphate dehydrogenase (G6PD) and acylglycerol kinase (AGK). Overexpression of Bcl-2 in the docetaxel-resistant PCa cells enhanced cell proliferation of docetaxel-resistant PCa cells under combination treatment. Analysis with qRT-PCR suggested that combination treatment decreased cholesterol biosynthesis genes DHCR24 (24-dehydrocholesterol reductase) and LSS (lanosterol synthase) but increased genes involved in glycolysis and TCA cycle.
CONCLUSIONS
Combination treatment of docetaxel with CAPE effectively suppressed the proliferation and survival of docetaxel-resistant PCa cells via inhibition of Bcl-2 and c-Myc as well as induction of metabolism interference. Combination treatment can be beneficial for patients with docetaxel-resistant PCa.
Topics: Androgen Antagonists; Animals; Apoptosis; Caffeic Acids; Cell Line, Tumor; Cell Proliferation; Docetaxel; Humans; Male; Mice; Mice, Nude; Phenylethyl Alcohol; Prostatic Neoplasms; Quality of Life
PubMed: 35197069
DOI: 10.1186/s12929-022-00797-z -
Thoracic Cancer Nov 2021To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer: A meta-analysis.
BACKGROUND
To investigate the efficacy and safety of apatinib alone or apatinib plus paclitaxel/docetaxel versus paclitaxel/docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC) through pooling of open published data.
METHODS
The electronic databases of Medline (1960-2021.5), Cochrane central register of controlled trials (CENTRAL), EMBASE(1980-2021.5) and Wan fang (1986-2021.5) were systematically searched by two reviewers to identify the relevant clinical trials related to the above subject. The objective response rate (ORR), disease control rate (DCR) and drug relevant adverse reactions were pooled and demonstrated by risk ratio (RR) and 95% confidence interval (95% CI). The statistical heterogeneity across studies was assessed by I-square test. The publication bias was evaluated by Egger's line regression test and demonstrated by Begg's funnel plot.
RESULTS
Eleven prospective studies were included in the meta-analysis. The pooled results indicated that the ORR (RR = 1.62, 95% CI: 1.32-2.00, p < 0.05) and DCR (RR = 1.29, 95% CI: 1.18-1.41, p < 0.05) of apatinib alone or apatinib plus paclitaxel/docetaxel was significantly higher than that of the paclitaxel/docetaxel group for advanced NSCLC, respectively. The drug-related adverse reaction was not statistically different between apatinib alone or apatinib plus paclitaxel/docetaxel with regard to the hand-foot syndrome, gastrointestinal reaction, thrombocytopenia, anemia and leukocytopenia (p > 0.05) except for hypertension (RR = 3.60, 95% CI: 1.26-10.31, p < 0.05). Subgroup analysis also indicated that the hypertension and hand-foot syndrome in apatinib + paclitaxel/docetaxel were higher than that of the paclitaxel/docetaxel group with a statistical difference (p < 0.05).
CONCLUSIONS
Apatinib alone or apatinib plus paclitaxel/docetaxel was superior to paclitaxel/docetaxel for ORR and DCR. However, combined treatment with apatinib appears to increase the risk of a patient developing an adverse reaction, especially hypertension and hand-foot syndrome.
Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Humans; Lung Neoplasms; Paclitaxel; Protein Kinase Inhibitors; Pyridines
PubMed: 34622571
DOI: 10.1111/1759-7714.14131