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In primary analysis, enzalutamide plus androgen deprivation therapy improved radiographic progression-free survival in patients with metastatic hormone-sensitive prostate cancer patients with metastatic hormone-sensitive prostate cancer; however, overall survival results were immature. Patients with mHSPC were randomly assigned 1:1 to either enzalutamide plus ADT or placebo plus ADT, stratified by disease severity and prior docetaxel use. After blindly failing 180 percentage-free patients randomly assigned to placebo plus ADT, the transition to open-label enzalutamide plus ADT was reversed. 154 of 574 patients randomly assigned to enzalutamide plus ADT as of May 28, 2021, and 202 of 576 patients randomly assigned to placebo plus ADT had died as a result of random chance ADT. Enzalutamide plus ADT reduced the risk of death by 34% compared to placebo plus ADT. Enzalutamide plus ADT continued to increase rPFS and other secondary end points. Enzalutamide plus ADT in patients with mHSPC prolongs life by a significant amount.
Source link: https://doi.org/10.1200/jco.22.00193
Purpose is a mismatch from a recent docetaxel therapy of metastatic prostate cancer patients has progressed to the hormone-sensitive stage of the disease. Different studies on docetaxel's toxicology in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients have contradicted. Moreover, serum docetaxel transporting 1-acid glycoprotein were measured, and docetaxel toxicity was determined. According to the plasma concentration versus time curve 1710 [coefficient of variation 28. 4%] and 1486 ng/mL*h, respectively, the docetaxel PK was not different between mCRPC and mHSPC patients, with areas under the plasma concentration curve 1710 [coefficient of variation 28. 4%] and 1486 ng/mL*h versus time curve 1710 [coefficient of variation 28. 4%]. In 50% of the mCRPC patients and 11% of the mHSPC patients, Docetaxel doses were reduced in 50% of the mCRPC patients and 11% of the mHSPC patients. Conclusions Docetaxel's PK profile was similar in mCPRC and mHSPC patients. According to the differences in docetaxel PK in our study population, there are no differences in toxicity between mCRPC and mHSPC patients.
Source link: https://doi.org/10.1007/s00280-022-04433-3
In 2020, prostate cancer is the second most common cancer among men worldwide. Metastatic prostate cancer patients have regular events such as pathologic fracture or spinal cord compression. Denosumab, a monoclonal antibody, blocks osteoclast-mediated bone resorption in bone metastasis from solid tumors and reduces bone turnover and destruction by bone resorption, inhibiting bone turnover and destruction. Case study Our patient is a 69-year-old man with extensive skeletal metastatic disease from primary prostate cancer who presented to the hospital complaining of generalized exhaustion and joint pain. On presentation, serum calcium was found to be dangerously poor at 5. 9 mg/dl, contributing to severe debilitating low back pain related to osteochondral lesions. The long-lived Denosumab's long elimination half-life, the repeat serum calcium level remained low at 6. 7 percent, which is likely. Denosumab's maximum serum drug concentration reaches 7 to 21 days after administration.
Source link: https://doi.org/10.1177/10781552211055407
Introduction: Epidemiologic investigations have uncovered a genetic imbalance in prostate cancer aggressiveness, but no definite consensus has been reached. Both bone metastases and hypertension were investigated in advanced PCa. In 25 patients with advanced PCa and bone metastases compared to 41 patients with advanced non-metastatic PCa, we investigated hypertension, hypercholesterolemia, and cardiovascular disease. Hypercholesterolemia was also strongly associated with active metastatic PCa. Metastatic PCa and vascular disease are linked in a significant association, according to the author.
Source link: https://doi.org/10.6000/1927-7229.2014.03.01.5
In vitro, we show that IFN treatment resulted in the expression of key histocompatibility class-I genes and PD-L1 in prostate cancer cells. In addition, IFN treatment resulted in a decrease in E-cadherin expression, which in turn raised resistance to chemotherapy in vitro. In an in vivo murine tumor model of spontaneous metastatic prostate cancer, IFN-A and decreased E-cadherin expression in the primary tumor, but more importantly in the metastatic site led to increased apoptosis and limited micrometastases in combination with paclitaxel therapy in combination with diffuse metastatic disease in both control and monotherapy treatment groups.
Source link: https://doi.org/10.1038/s41598-022-10724-9
Background PSMA PET is a commonly used tool for staging prostate cancer patients. In addition, interest in using PET results for personalized local treatment plans in surgery and radiotherapy, especially for focus treatment strategies is on the rise. Methods This is a retrospective review of 135 patients with non-metastatic prostate cancer and PSMA PET before any medical treatment was administered. For all measurements except ASP, which did not have a significant relationship with Gleason scores, a low to moderate, but significant, correlation of imaging parameters with PSA values and Gleason scores was found. AUC tests comparing quantitative PET results by DeLong test showed significant improvement of SUV max for the detection of high-risk patients relative to SUV means. Conclusion Our results confirm prior studies with a smaller number of patients that reported moderate correlations of PSMA PET parameters with clinical risk factors.
Source link: https://doi.org/10.3389/fonc.2022.879089
When added to androgen deprivation therapy in patients with newly diagnosed metastatic hormone-sensitive prostate cancer, we investigated the clinical value of orteronel. paraphrasedoutput:METHODS Participants with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel or ADT with bicalutamide in this open-label randomized phase III study. RESULTS Among the 1,279 patients included in the study, 638 were randomly assigned to the ADT plus orteronel arm and 641 to the control arm, with 638 being assigned to the control arm. Patients in the control arm and 63% of patients in the orteronel arm received 77. 4% of patients and 61. 3% in the orteronel arm. CONCLUSION The report did not meet the primary end point of improved OS with orteronel. The lack of a connection between PFS and PSA responses with OS has sparked questions about the possibility that OS is a source of increased postprotocol therapy in this context.
Source link: https://doi.org/10.1200/jco.21.02517
We present a comprehensive therapeutic and biomarker analysis of a large cohort of chemotherapy-resistant, metastatic castrate resistant prostate cancer patients derived xenografts and organoids in this large cohort. In 70% of models, In vitro and in vivo therapy using an anti-B7H3 specific antibody conjugated to a pyrrolobenzodiazepine cytotoxic agent was safe. The presence of SLFN11 in SCNPC and adenocarcinoma models correlated perfectly with vulnerability, but an absence of SLFN11 was not predictive. We also found that vulnerable models were specifically linked to the loss of specific downstream DNA repair proteins. In about 70% of mPC clinical samples, the above biomarkers are present in toto, indicating a wide potential for mechanistically compatible therapy of tumors with new regimens. One Sentence Summary B7H3-PBD-ADC's sensitivity to metastatic prostate cancer is attributed to replication stress, SLFN11 expression related to interferon signaling, and changes in specific DNA repair factors.
Source link: https://doi.org/10.1101/2022.04.19.488784
Abstract Docetaxel chemotherapy is a common treatment strategy for metastatic castrate resistant prostate cancer patients. However, the clonal variation of these key driver cancer genes during chemotherapy in mCRPC patients has yet to be described. We performed a retrospective review of cell-free DNA alterations in blood samples collected from mCRPC patients before and after starting chemotherapy, with results and clinical outcomes being monitored. In the clinical setting, the ability to monitor these driver gene clonal changes during chemotherapy may be useful.
Source link: https://doi.org/10.1038/s41598-022-08520-6
Abstract The unique microenvironment of the prostate plays a vital role in prostate cancer formation and progression. In a typical orthotopic xenograft model, we investigated the effects of cancer-associated fibroblasts on PCa progression using patient-derived fibroblast primary cultures. Tumor formation was similar to tumor cells alone when NCAFs or BPHFs were coinjected. Compared to injection of LNCaP cells alone, all three fibroblast types in LNCaP xenografts significantly accelerated primary tumor formation in LNCaP xenografts. This is the first research using an orthotopic spheroid culture xenograft model to demonstrate a positive effect of patient-derived CAFs on PCa growth.
Source link: https://doi.org/10.1038/s41598-020-69424-x
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