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Journal of Comparative Effectiveness... Feb 2023In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was... (Meta-Analysis)
Meta-Analysis Review
In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was conducted to compare the relative efficacy of these treatments. A systematic literature review of randomized controlled trials evaluating first-line-to-progression and second-line treatments for advanced NsqNSCLC informed Bayesian NMAs for overall survival (OS) and progression-free survival (PFS) end points. Among first-line-to-progression treatments, pembrolizumab + pemetrexed + platinum showed the greatest OS benefit versus other regimens and a PFS benefit versus all but three regimens. Among second-line treatments, an OS benefit was seen for atezolizumab, nivolumab and pembrolizumab versus docetaxel. Pembrolizumab + pemetrexed + platinum showed the maximum OS benefit in the first-line setting. In the second-line setting, anti-PD-1/anti-PD-L1 monotherapies were better than docetaxel.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Docetaxel; Pemetrexed; Network Meta-Analysis; Platinum; Bayes Theorem; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36621905
DOI: 10.2217/cer-2022-0016 -
Scientific Reports Mar 2021Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin....
Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Docetaxel; Doxorubicin; Female; Humans; Triple Negative Breast Neoplasms; Xenograft Model Antitumor Assays
PubMed: 33782404
DOI: 10.1038/s41598-021-85962-4 -
Drug Design, Development and Therapy 2022To evaluate the prostate cancer therapy efficiency of the synergistic combination docetaxel (DTX) and formononetin (FMN) in one nano-sized drug delivery system....
Prostate Cancer Therapy Using Docetaxel and Formononetin Combination: Hyaluronic Acid and Epidermal Growth Factor Receptor Targeted Peptide Dual Ligands Modified Binary Nanoparticles to Facilitate the in vivo Anti-Tumor Activity.
OBJECTIVE
To evaluate the prostate cancer therapy efficiency of the synergistic combination docetaxel (DTX) and formononetin (FMN) in one nano-sized drug delivery system. Hyaluronic acid (HA) and epidermal growth factor receptor-targeted peptide (GE11) dual ligands were applied to modify the nano-systems.
METHODS
In this study, GE11-modified nanoparticles (GE-NPs) were applied for the loading of DTX, and HA-decorated NPs (HA-NPs) were used to encapsulate FMN. HA and GE11 dual ligand-modified binary nanoparticles (HAGE-DTX/FMN-NPs) were constructed by the self-assembling of GE-NPs and HA-NPs. The anti-PCa ability of the system was evaluated in vitro on PC-3 human prostate carcinoma cells (PC3 cells) and in vivo on PC3 tumor-bearing mice in comparison with single NPs and free drugs formulations.
RESULTS
HA/GE-DTX/FMN-NPs were nano-sized particles with smaller particles coating on the inner core and achieved a size of 189.5 nm. HA/GE-DTX/FMN-NPs showed a cellular uptake efficiency of 59.6%, and a more efficient inhibition effect on PC3 cells compared with single ligand-modified NPs and free drugs. HA/GE-DTX/FMN-NPs showed significantly higher tumor inhibition efficiency than their single drug-loaded counterparts and free drugs.
CONCLUSION
HA/GE-DTX/FMN-NPs have a synergistic anti-tumor effect and also could the reduce unexpected side effects during the cancer therapy. It could be used as a promising anti-PCa system.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Docetaxel; Drug Carriers; ErbB Receptors; Humans; Hyaluronic Acid; Isoflavones; Ligands; Male; Mice; Nanoparticles; Peptides; Prostate; Prostatic Neoplasms; Taxoids
PubMed: 35983428
DOI: 10.2147/DDDT.S366622 -
Deutsches Arzteblatt International Sep 2022For many years, the standard treatment of metastatic, hormone-sensitive prostatic carcinoma (mHSPC) was androgen deprivation therapy (ADT) alone. By lowering the...
BACKGROUND
For many years, the standard treatment of metastatic, hormone-sensitive prostatic carcinoma (mHSPC) was androgen deprivation therapy (ADT) alone. By lowering the testosterone level into the castration range, ADT deprives the tumor of a key growth factor.
METHODS
For this article, we evaluated the treatment recommendations contained in national and international guidelines (German S3 guidelines and those of the European Society for Medical Oncology [ESMO], European Association of Urology [EAU], and National Comprehensive Cancer Network [NCCN]), as well as pertinent publications revealed by a PubMed search and the congress abstracts of the ESMO and of the American Society of Clinical Oncology [ASCO].
RESULTS
The past few years have witnessed fundamental changes in the treatment of mHSPC. Treatment intensification with docetaxel or with the new drugs directed against the androgen receptor signal pathway (abiraterone, apalutamide and enzalutamide) has been found to lower mortality by 19-40% and is now an integral component of first-line therapy. Relevant new findings have also been obtained with threefold combinations of ADT, docetaxel, and abiraterone or darolutamide. For patients with a light tumor burden, local radiotherapy of the primary tumor improves the probability of survival at 3 years by 8% (45.4 versus 49.1 months, difference 3.6 months; 95% confidence interval, 1.0 to 6.2 months).
CONCLUSION
The treatment of mHSPC is constantly changing. Phase III trials that are now in the recruitment stage, as well as our continually improving understanding of the underlying molecular-pathological mechanisms, will be altering the treatment landscape still further in the years to come.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Docetaxel; Carcinoma; Hormones
PubMed: 35912436
DOI: 10.3238/arztebl.m2022.0294 -
BMC Cancer Jun 2023The CARD trial was conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who had received docetaxel and experienced disease progression...
Real-world effectiveness of third-line cabazitaxel in patients with metastatic castration-resistant prostate cancer: CARD-like analysis of data from a post-marketing surveillance in Japan.
BACKGROUND
The CARD trial was conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who had received docetaxel and experienced disease progression within 1 year on an androgen receptor-axis-targeted therapy (ARAT). Subsequent treatment with cabazitaxel had improved clinical outcomes compared with an alternative ARAT. This study aims to confirm the effectiveness of cabazitaxel in real-world patients in Japan and compare their characteristics with those of patients from the CARD trial.
METHODS
This was a post-hoc analysis of a nationwide post-marketing surveillance registering all patients who were prescribed cabazitaxel in Japan between September 2014 and June 2015. Included patients had received docetaxel and ≤ 1 year of an ARAT (abiraterone or enzalutamide) prior to receiving cabazitaxel or an alternative ARAT, as their third-line therapy. The primary effectiveness endpoint was the time to treatment failure (TTF) of the third-line therapy. Patients were matched (1:1) from the cabazitaxel and second ARAT arms based on propensity score (PS).
RESULTS
Of the 535 patients analysed, 247 received cabazitaxel and 288 the alternative ARAT as their third-line therapy, of which, 91.3% (n = 263/288) received abiraterone and 8.7% (n = 25/288) received enzalutamide as their second third-line ARAT. Patients in the cabazitaxel and second ARAT arms had TNM classification of M1 or MX in 73.3% and 68.1%, Gleason score of 8-10 in 78.5% and 79.2% and mean (standard deviation) serum PSA levels of 483 (1370) and 594 (1241) ng/mL, respectively. Initial cabazitaxel dose was ≤ 20 mg/m in 61.9% (n = 153/247) of the patients in the cabazitaxel arm. The median TTF (95% confidence interval [CI]) of the third-line therapy was 109 (94-128) days for cabazitaxel and 58 (57-66) days for the second ARAT, with a hazard ratio (95% CI) of 0.339 (0.279-0.413) favouring cabazitaxel. Similar results were obtained after PS-matching, with a hazard ratio (95% CI) of 0.323 (95% CI 0.258-0.402) favouring cabazitaxel.
CONCLUSIONS
Consistent with the CARD trial, cabazitaxel demonstrated superior effectiveness over a second alternative ARAT in a real-world patient population in Japan, despite the population having more advanced disease status and a lower dose of cabazitaxel being more frequently administered, than in the CARD trial.
Topics: Male; Humans; Docetaxel; Japan; Prostatic Neoplasms, Castration-Resistant; Product Surveillance, Postmarketing
PubMed: 37308888
DOI: 10.1186/s12885-023-10998-w -
The Korean Journal of Internal Medicine Nov 2020We evaluated the efficacy of docetaxel and epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer and assessed the predictive factors for response to...
BACKGROUND/AIMS
We evaluated the efficacy of docetaxel and epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer and assessed the predictive factors for response to neoadjuvant chemotherapy and prognostic factors related to relapse-free survival.
METHODS
Forty patients who received docetaxel and epirubicinas neoadjuvant chemotherapy for locally advanced breast cancer were evaluated retrospectively. Neoadjuvant chemotherapy consisted of intravenous injection of 75 mg/m2 docetaxel and 60 mg/m2 epirubucin on day 1, every 21 days, and two to six cycles.
RESULTS
Twenty-five (62.5%) patients showed a partial response, and 15 (37.5%) patients showed a stable disease in the first response evaluation after two or three cycles of neoadjuvant chemotherapy. In the second response evaluation of nine patients who received six cycles of neoadjuvant chemotherapy, one patient achieved a complete response, but two patients with hormone receptor-negative, human epidermal growth factor receptor 2-positive breast cancer experienced disease progression. Twenty-five (62.5%) patients experienced downstaging after neoadjuvant chemotherapy. Patients with > 20% pretreatment Ki-67 and decrease of Ki-67 between pre- and post-neoadjuvant chemotherapy showed a trend for better response. In multivariate analysis, advanced pathological stage showed a significant negative effect on relapse-free survival.
CONCLUSION
Docetaxel and epirubicin neoadjuvant chemotherapy showed a good response in locally advanced breast cancer. Pretreatment Ki-67 and change of Ki-67 may play a role as predictive factor for response to neoadjuvant chemotherapy.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Epirubicin; Female; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Retrospective Studies; Taxoids; Treatment Outcome; Young Adult
PubMed: 32069523
DOI: 10.3904/kjim.2019.031 -
Molecules (Basel, Switzerland) May 2024Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, and chemotherapy,...
Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, and chemotherapy, but these come with side effects and limitations. Researchers are exploring natural compounds like baicalin and baicalein, derived from the plant, as potential complementary therapies. This study investigated the effects of baicalin and baicalein on the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel, commonly used chemotherapeutic drugs for breast cancer. The analysis included breast cancer cells (MCF-7) and human endothelial cells (HUVEC-ST), to assess potential effects on healthy tissues. We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein. Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells. In comparison, their effects on endothelial cells were mixed and depended on concentration and time. The results suggest that baicalin and baicalein might be promising complementary agents to improve the efficacy of doxorubicin and docetaxel anticancer activity. However, further research is needed to validate their safety and efficacy in clinical trials.
Topics: Humans; Flavonoids; Flavanones; Docetaxel; Doxorubicin; MCF-7 Cells; Apoptosis; Breast Neoplasms; Female; DNA Damage; Drug Synergism; Antineoplastic Agents; Cell Survival; Human Umbilical Vein Endothelial Cells
PubMed: 38893380
DOI: 10.3390/molecules29112503 -
Arteriosclerosis, Thrombosis, and... May 2023The recent identification of the cell-surface protein DSC1 (desmocollin 1) as a negative regulator of HDL (high-density lipoprotein) biogenesis has attracted us to... (Review)
Review
The recent identification of the cell-surface protein DSC1 (desmocollin 1) as a negative regulator of HDL (high-density lipoprotein) biogenesis has attracted us to revisit the old HDL biogenesis hypothesis: HDL biogenesis reduces atherosclerosis. The location and function of DSC1 suggest that DSC1 is a druggable target for the promotion of HDL biogenesis, and the discovery of docetaxel as a potent inhibitor of the DSC1 sequestration of apolipoprotein A-I has provided us with new opportunities to test this hypothesis. The FDA-approved chemotherapy drug docetaxel promotes HDL biogenesis at low-nanomolar concentrations that are far lower than used in chemotherapy. Docetaxel has also been shown to inhibit atherogenic proliferation of vascular smooth muscle cells. In accordance with these atheroprotective effects of docetaxel, animal studies have shown that docetaxel reduces dyslipidemia-induced atherosclerosis. In the absence of HDL-directed therapies for atherosclerosis, DSC1 constitutes an important new target for the promotion of HDL biogenesis, and the DSC1-targeting compound docetaxel serves as a model compound to prove the hypothesis. In this brief review, we discuss opportunities, challenges, and future directions for using docetaxel in the prevention and treatment of atherosclerosis.
Topics: Animals; Lipoproteins, HDL; Docetaxel; Atherosclerosis; Cholesterol, HDL
PubMed: 36861478
DOI: 10.1161/ATVBAHA.122.318275 -
British Journal of Clinical Pharmacology Feb 2023We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure.
AIMS
We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure.
METHODS
A PK/PD study was performed in 27 early breast cancer patients treated with doxorubicin and cyclophosphamide for 4 cycles followed by 4 cycles of docetaxel 75-100 mg/m infused every 21 days. Individual Bayesian estimates of docetaxel PK parameters were obtained using a nonparametric population PK model developed with data from patients with metastatic breast cancer who received dose-intensified docetaxel (300-350 mg/m ). Docetaxel area under the curve (AUC) and maximum concentration (Cmax) in each cycle and total cumulative AUC (AUCcum) were calculated and related to the incidence of adverse effects and tumour recurrence.
RESULTS
Docetaxel clearance showed no change over the 4 treatment cycles, but a gradual increase in the volume of distribution was observed. One third of the patients had at least 1 dose reduction of docetaxel due to toxicity. The mean AUC, AUCcum and Cmax in patients showing docetaxel-associated adverse events were significantly higher than in patients free of toxicity (P < .05). Fatigue and decrease in haemoglobin and haematocrit levels were related to docetaxel AUC and Cmax and pain to AUC. AUC and Cmax >4.5 mg*h/L and 3.5 mg/L, respectively, were risk factors for docetaxel toxicity, while an AUC <4.5 mg*h/L was associated with tumour recurrence.
CONCLUSION
We report for the first time a relation between docetaxel exposure and toxicity and recommend specific targets of drug exposure with implications for the clinical management of early breast cancer patients.
Topics: Humans; Female; Docetaxel; Breast Neoplasms; Neoplasm Recurrence, Local; Bayes Theorem; Taxoids; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36098504
DOI: 10.1111/bcp.15526 -
Gastric Cancer : Official Journal of... Nov 2023A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587-0.871; p = 0.0008). This final report analyzed 5-year survival outcomes along with the incidence and pattern of late recurrences.
PATIENTS AND METHODS
Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed.
RESULTS
Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613-0.922; p = 0.0059). The incidence of late recurrence at > 3 years after randomization was similar in both groups (7.3% versus 7.2%). Peritoneal dissemination was the most common pattern of late recurrence. Addition of docetaxel significantly suppressed relapse through the lymphatic (6.8% [95% CI 4.52-9.17] versus 15% [95% CI 11.76-18.30]; p < 0.0001) and hematogenous (10.2% [95% CI 7.37-12.94] versus 15.7% [95% CI 12.36-19.01]; p < 0.0137) pathways throughout the 5 years of follow-up.
CONCLUSION
The survival benefit of postoperative chemotherapy with S-1 and docetaxel in terms of 5-year overall survival rate was confirmed for patients with pathologically Stage III gastric cancer, although late recurrences were not prevented.
Topics: Humans; Stomach Neoplasms; Docetaxel; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Proportional Hazards Models; Neoplasm Staging; Gastrectomy
PubMed: 37548812
DOI: 10.1007/s10120-023-01419-9