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Medicine Sep 2016Recently, increasing relevant studies researched the efficacy of castration resistant prostate cancer (CRPC) patients using chemotherapy with or without estramustine, in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recently, increasing relevant studies researched the efficacy of castration resistant prostate cancer (CRPC) patients using chemotherapy with or without estramustine, in order to assess the efficacy and toxicity of combining estramustine with chemotherapy for the treatment of CRPC.
METHODS
Relevant randomized clinical trials were systematically searched from the databases Pubmed, Embase, and Web of science up to April 1, 2016. Data were centrally extracted and analyzed from the previous studies by 2 independent reviewers. The primary endpoint was overall survival (OS) with pooled hazard ratios. Secondary endpoints were prostate-specific antigen (PSA) response and grade 3 or 4 toxicity using pooled odds ratios. Stata version 12.0 software was used for statistical analysis.
RESULTS
Overall, this meta-analysis identified 9 eligible articles, including a total of 956 patients, who had been accrued between January 1, 1993 and December 1, 2010 and randomly divided into chemotherapy with estramustine and without estramustine. Chemotherapy (with or without estramustine) consisted of docetaxel, paclitaxel, ixabepilone, epirubicin, and vinblastine. Patients who received chemotherapy with estramustine had a better improvement in PSA response rate, comparing those without estramustine (OR = 1.84, 95% CI = 1.20-2.80). However, OS between the 2 groups indicated no significant differences (HR = 0.90, 95% CI = 0.77-1.05). Besides, these results of meta-analysis showed no obvious differences between these 2 groups in grade 3 or 4 adverse effects, including anemia (OR = 0.78, 95% CI = 0.38-1.57), neutropenia (OR = 0.91, 95% CI = 0.59-1.43), thrombocytopenia (OR = 0.68, 95% CI = 0.19-2.42), nausea (OR = 2.34, 95% CI = 0.81-6.72), vomiting (OR = 2.43, 95% CI = 0.69-8.51), diarrhea (OR = 3.45, 95% CI = 0.93-12.76), fatigue (OR = 0.67, 95% CI = 0.32-1.41), neuropathy (OR = 0.54, 95% CI = 0.21-1.44), allergic reaction (OR = 1.60, 95% CI = 0.37-6.84), thromboembolic event (OR = 2.18, 95% CI = 0.86-5.51), and edema (OR = 1.02, 95% CI = 0.18-5.95).
CONCLUSIONS
This meta-analysis indicated chemotherapy with additional estramustine increased the PSA response rate. However, OS and grade 3 or 4 toxicity were not improved for these patients with CRPC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Estramustine; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 27684806
DOI: 10.1097/MD.0000000000004801 -
World Journal of Clinical Oncology Aug 2015There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often... (Review)
Review
There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.
PubMed: 26266099
DOI: 10.5306/wjco.v6.i4.35 -
International Journal of Surgery... Aug 2018The aim of this study was to compare the efficacy and safety of docetaxel, cabazitaxel, docetaxel + estramustine, mitoxantrone in the management of... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
The aim of this study was to compare the efficacy and safety of docetaxel, cabazitaxel, docetaxel + estramustine, mitoxantrone in the management of castration-resistant prostate cancer (CRPC).
METHODS
Electronic databases including PubMed, Cochrance Library and Embase were searched for studies published from when the databases were established to January 1st, 2018. Randomized controlled trials (RCTs) that compared docetaxel + prednisone (DP), cabazitaxel + prednisone (CP), docetaxel + estramustine + prednisone (DEP), and mitoxantrone + cabazitaxel + prednisone (MP) for CRPC treatment were identified. The network meta-analysis was conducted with software R 3.3.2. We analyzed the main outcomes, including the overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) response, tumor response and severe adverse events (AEs). Ranking of the chemotherapeutic agents was based on probabilities of interventions for each of the outcomes that were performed. The consistency of direct and indirect evidence was assessed by node splitting.
RESULTS
10 RCTs, with 3590 patients, were analyzed. The network meta-analysis results revealed that CP significantly increased OS, PFS, PSA response, tumor response, and severe AEs compared to MP. DP showed similar results with CP except for tumor response, where it showed slight inferiority in effectiveness. DEP was associated with clearly improved outcomes in PFS, PSA response and tumor response compared to those of MP, but this was not the case for OS benefit and severe AEs. No significant difference was detected in DP, CP and DEP except for the outcomes of severe AEs. MP was less effective in survival and clinical benefit, but much safer in safety outcomes than other chemotherapy agents. The probabilities of rank plots showed that CP ranked first in OS and tumor response; DEP ranked first in PFS time and PSA response; MP was the best treatment mode for safety.
CONCLUSIONS
DP and CP survival benefit (OS, PFS) and clinical benefit (PSA response and tumor response) were comparable, as well as their associated AEs. DEP was associated with less survival benefit, similar clinical improvement and more AEs than DP or CP. MP had the lowest survival and clinical benefit but excellent safety than other agents. Based on evidences of current results, we recommended CP as the most suitable chemotherapy agent for CRPC patients, followed by DP, MP as third, and DEP as the last choice. However, considering limitations of our network meta-analysis, additional high-quality studies are needed for further evaluation.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Estramustine; Humans; Male; Middle Aged; Mitoxantrone; Network Meta-Analysis; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Taxoids; Treatment Outcome
PubMed: 29906643
DOI: 10.1016/j.ijsu.2018.06.010 -
Cellular Physiology and Biochemistry :... 2013The nitrogen mustard derivative of estradiol-17β-phosphate estramustine is used for the treatment of prostate cancer. Estramustine may trigger suicidal death of cancer...
BACKGROUND
The nitrogen mustard derivative of estradiol-17β-phosphate estramustine is used for the treatment of prostate cancer. Estramustine may trigger suicidal death of cancer cells. Side effects of estramustine include anemia. At least in theory, estramustine could cause anemia by stimulation of eryptosis, the suicidal death of erythrocytes. Hallmarks of eryptosis include cell shrinkage, increased cytosolic Ca2+ activity ([Ca2+]), ceramide formation and phosphatidylserine translocation to the outer leaflet of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Eryptosis is stimulated by increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether estramustine triggers eryptosis.
METHODS
[Ca2+]i was estimated from Fluo3 fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding, and hemolysis from hemoglobin release.
RESULTS
A 24 h exposure to estramustine (≤ 100 μM) significantly increased [Ca2+]i, increased annexin V binding and increased hemoglobin release. The effect of estramustine on annexin V binding was significantly blunted by removal of extracellular Ca2+.
CONCLUSIONS
Estramustine stimulates both, eryptosis and hemolysis. The estramustine induced translocation of phosphatidylserine to the cell surface is at least partially due to increase of cytosolic Ca2+ activity.
Topics: Annexin A5; Antineoplastic Agents, Hormonal; Calcium; Cell Death; Cell Size; Ceramides; Cytosol; Erythrocytes; Estramustine; Humans; Phosphatidylserines
PubMed: 24296399
DOI: 10.1159/000356580 -
Prostate Cancer and Prostatic Diseases Jun 2016Contemporary therapies for metastatic castration-resistant prostate cancer (mCRPC) have shown survival improvements, which do not account for patient experience and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Contemporary therapies for metastatic castration-resistant prostate cancer (mCRPC) have shown survival improvements, which do not account for patient experience and health-related quality of life (HRQoL).
METHODS
This literature review included a search of MEDLINE for randomized clinical trials enrolling ⩾50 patients with mCRPC and reporting on patient-reported outcomes (PROs) since 2010.
RESULTS
Nineteen of 25 publications describing seven treatment regimens (10 clinical trials and nine associated secondary analyses) met the inclusion criteria and were critically appraised. The most commonly used measures were the Functional Assessment of Cancer Therapy-Prostate (n=5 trials) and Brief Pain Inventory Short Form (n=4 trials) questionnaires. The published data indicated that HRQoL and pain status augmented the clinical efficacy data by providing a better understanding of treatment impact in mCRPC. Abiraterone acetate and prednisone, enzalutamide, radium-223 dichloride and sipuleucel-T offered varying levels of HRQoL benefit and/or pain mitigation versus their respective comparators, whereas three treatments (mitoxantrone, estramustine phosphate and docetaxel, and cabazitaxel) had no meaningful impact on HRQoL or pain. The main limitation of the data were that the PROs utilized were not developed for use in mCRPC patients and hence may not have comprehensively captured symptoms important to this population.
CONCLUSIONS
Recently published randomized clinical trials of new agents for mCRPC have captured elements of the patient experience while on treatment. Further research is required to standardize methods for measuring, quantifying and reporting on HRQoL and pain in patients with mCRPC in the clinical practice setting.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Humans; Immunotherapy; Male; Neoplasm Metastasis; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Treatment Outcome
PubMed: 26832363
DOI: 10.1038/pcan.2015.42 -
The Oncologist 2011The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy and durability with currently available... (Review)
Review
The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy and durability with currently available therapeutics. The epothilones represent a novel class of anticancer therapy that stabilizes microtubules, causing cell death and tumor regression in preclinical models. The structure of the tubulin-binding site for epothilones is distinct from that of the taxanes. Moreover, preclinical studies suggest nonoverlapping mechanisms of resistance between epothilones and taxanes. In early-phase studies in patients with CRPC, treatment with ixabepilone, a semisynthetic analog of epothilone B, induced objective responses and prostate-specific antigen declines in men previously progressing on docetaxel-based regimens. Clinical activity has been observed in nonrandomized trials for patients with CRPC using ixabepilone in the first- and second-line settings as a single agent and in combination with estramustine. Patupilone and sagopilone were also shown to have promising efficacy in phase II clinical trials of patients with CRPC. All three epothilones appear to be well tolerated, with modest rates of neutropenia and peripheral neuropathy. The lack of crossresistance between epothilones and taxanes may allow sequencing of these agents. Evaluating epothilones in phase III comparative trials would provide much-needed insight into their potential place in the management of patients with CRPC.
Topics: Epothilones; Humans; Male; Prostatic Neoplasms
PubMed: 21964003
DOI: 10.1634/theoncologist.2010-0014 -
The New England Journal of Medicine Oct 2004Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer.
METHODS
We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels.
RESULTS
Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups.
CONCLUSIONS
The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Resistance, Neoplasm; Estramustine; Follow-Up Studies; Humans; Male; Middle Aged; Mitoxantrone; Palliative Care; Prednisone; Prostatic Neoplasms; Quality of Life; Survival Analysis; Taxoids
PubMed: 15470214
DOI: 10.1056/NEJMoa041318 -
Cancer Feb 2007Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and... (Review)
Review
Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single-agent activity in HRPC. Next-generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum-based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum-based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression-free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second-line chemotherapy. Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second-line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Neoplasms, Hormone-Dependent; Organoplatinum Compounds; Prostatic Neoplasms
PubMed: 17186531
DOI: 10.1002/cncr.22439 -
Archivos Espanoles de Urologia Sep 2019Estramustine is an stable estradiol and nitrogenated mustard conjugatewith antymicotic properties. Currently, with the appearance of chemotherapy and new molecules,... (Review)
Review
OBJECTIVE
Estramustine is an stable estradiol and nitrogenated mustard conjugatewith antymicotic properties. Currently, with the appearance of chemotherapy and new molecules, estramustin acetate is not a drug of choice for castration resistant prostate cancer.
METHODS
We describe two patients with castration resistant prostate cancer under treatment with estramustine acetate and complete biochemical response and stable disease. We review the literature to elucidate if the drug should be stopped and changed for the new molecules that have demonstrated survival increase.
RESULTS
To our knowledge, there are not data in the literature to either solve the questions posed or shed light regarding cumulative toxicity due to prolongued use of estramustine acetate.
CONCLUSIONS
We recognize that these clinical cases do not translate that estramustine acetate is a first line treatment for patients with CRPC. Nevertheless, they translate the heterogeneity of CRPC. It would be interesting to investigate the combination of new agents with estramustine acetate as well as the search of biomarkers that enable selection of candidates who could respond to estramustine acetate.
Topics: Antineoplastic Agents, Alkylating; Estramustine; Humans; Male; Prostatic Neoplasms
PubMed: 31475684
DOI: No ID Found -
Asian Journal of Andrology 2017Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC) has changed the... (Review)
Review
Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC) has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA). However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Disease Progression; Estramustine; Flutamide; Humans; Kallikreins; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant
PubMed: 27270339
DOI: 10.4103/1008-682X.179159