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Drug Intelligence & Clinical Pharmacy May 1984Estramustine phosphate is approved by the Food and Drug Administration for oral use in the palliative treatment of patients with metastatic and/or progressive carcinoma... (Clinical Trial)
Clinical Trial Review
Estramustine phosphate is approved by the Food and Drug Administration for oral use in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a conjugate of 17 beta-estradiol and the carbamate of nitrogen mustard. Although its therapeutic efficacy has been demonstrated, it is not clear to what extent each constituent contributes to estramustine's effectiveness. Estramustine phosphate therapy achieves objective response rates of 60-90 percent in advanced stage D prostatic cancer patients with no prior hormonal therapy. These results are consistent with those obtained with conventional hormonal therapy in similar patient populations. Therapeutic efficacy does not appear to increase when estramustine is used concurrently with other cytotoxic chemotherapeutic agents. An objective response rate of 20-30 percent can be anticipated in patients refractory to conventional hormonal therapy. It is in this group, the estrogen-resistant patients, that estramustine shows the most promise. Adverse effects of estramustine are similar to those of diethylstilbestrol. Gastrointestinal and cardiovascular side effects appear to be the most important and may be severe enough to require discontinuation of therapy.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular System; Clinical Trials as Topic; Costs and Cost Analysis; Digestive System; Estramustine; Female; Humans; Kinetics; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms
PubMed: 6373212
DOI: 10.1177/106002808401800502 -
General Pharmacology Aug 1999Estramustine (EM), a conjugate of nornitrogen mustard and estradiol, is a antimicrotubule drug currently in use for the treatment of advanced prostatic carcinoma.... (Review)
Review
Estramustine (EM), a conjugate of nornitrogen mustard and estradiol, is a antimicrotubule drug currently in use for the treatment of advanced prostatic carcinoma. Experimental data are accumulating concerning the antitumor effect of EM in other malignancies, and clinical studies in other malignancies are ongoing. This review summarizes the information available to date concerning the effects of EM and the development of drug resistance. EM depolymerizes microtubules by binding to microtubule-associated proteins (MAPs) as well as tubulin. Because of the radiosensitizing effect of this drug there has been a recent increase in interest concerning estramustine and its clinical use. Recently, it was proposed that EM induces an apoptotic cell death in glioma cells in vitro and in a rat model. EM resistance is distinct from MDR phenotype; it has been used in combination with antimitotic agents which are part of the MDR phenotype. Observations made with estramustine-resistant cell lines show the acquisition of estramustine resistance is a function of multiple adaptation by changes at tubulin expression pattern, and is also associated with changes in tau expression and phosphorylation.
Topics: Animals; Antineoplastic Agents, Hormonal; Drug Resistance, Neoplasm; Estramustine; Male; Microtubule-Associated Proteins; Prostatic Neoplasms; Rats; Tubulin; tau Proteins
PubMed: 10461848
DOI: 10.1016/s0306-3623(98)00272-9 -
Cancer Treatment and Research 1995
Review
Topics: Animals; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Estramustine; Humans; Male; Prostatic Neoplasms
PubMed: 8595142
DOI: 10.1007/978-1-4615-2007-8_8 -
Journal of Neuro-oncology Oct 1996Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma.... (Review)
Review
Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramustine has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demonstrated for other carbamate esters. Estramustine does not impair proliferation of nonneoplastic astrocytes at concentrations that inhibit glioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulation of estramustine in human glioma tissue have been demonstrated. Estramustine has been shown to enhance the cytotoxic effects of irradiation in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an anti-mitotic drug but recently other effects such as inhibition of DNA synthesis, induction of apoptosis, and membrane alterations have been shown. This report summarizes the preclinical observations concerning the effects of estramustine and related compounds on human malignant gliomas. These findings form the basis for proposing further laboratory and clinical investigation regarding estramustine and human malignant gliomas.
Topics: Animals; Antineoplastic Agents, Hormonal; Brain Neoplasms; Carrier Proteins; Estramustine; Glioma; Humans; Molecular Structure; Prostatic Secretory Proteins; Radiation-Sensitizing Agents
PubMed: 8865006
DOI: 10.1007/BF00177446 -
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 -
Seminars in Urologic Oncology Feb 1997Long misclassified as an alkylating agent, estramustine phosphate is a stable conjugate of estradiol and nornitrogen mustard with antimitotic properties. Binding of the... (Review)
Review
Long misclassified as an alkylating agent, estramustine phosphate is a stable conjugate of estradiol and nornitrogen mustard with antimitotic properties. Binding of the drug to microtubule-associated proteins, tubulin, and proteins of the nuclear matrix are presently considered to be the most likely mechanisms underlying the cytotoxicity of estramustine in androgen-independent prostatic carcinoma. Identification of these mechanisms of action has led to clinical reevaluation of estramustine phosphate (EMP) in several rationally designed drug combinations. Combination of EMP with either vinblastine, paclitaxel or etoposide has produced antitumor responses in 30% to 60% of patients with metastatic hormone-refractory prostate carcinoma as determined by reduction in bidimensionally measurable soft tissue disease, pain, and serum prostate-specific antigen. Whereas the antitumor activity of the combinations has been greater than additive for the single agents, the toxicities of treatment have not been greater than predicted for the individual drugs. The promising results of EMP-based chemotherapy encourage additional laboratory and clinical investigations to develop more effective therapy for hormone-refractory disease and for selected patients with earlier stages of prostate cancer.
Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Screening Assays, Antitumor; Estramustine; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms
PubMed: 9050135
DOI: No ID Found -
Pharmacology & Therapeutics 1989
Review
Topics: Animals; Estramustine; Humans; Microtubules; Mitosis; Nitrogen Mustard Compounds
PubMed: 2682681
DOI: 10.1016/0163-7258(89)90012-0 -
International Urology and Nephrology 1989This review presents the most important hormonal, cytotoxic and pharmacokinetic properties of estramustine phosphate. Furthermore the results of randomized Phase III... (Review)
Review
This review presents the most important hormonal, cytotoxic and pharmacokinetic properties of estramustine phosphate. Furthermore the results of randomized Phase III trials are described in patients with hormone refractory prostatic cancer with and without previous irradiation. Several randomized studies are reported with Estracyt also in the primary treatment of this disease.
Topics: Estramustine; Humans; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms
PubMed: 2693392
DOI: 10.1007/BF02559635 -
Drugs & Aging Jul 1995Estramustine phosphate sodium (estramustine phosphate), a unique antitumour agent, is selectively taken up by prostate cells and exerts antineoplastic effects by... (Review)
Review
Estramustine phosphate sodium (estramustine phosphate), a unique antitumour agent, is selectively taken up by prostate cells and exerts antineoplastic effects by interfering with microtubule of dynamics and by reducing plasma levels of testosterone. In noncomparative studies of estramustine phosphate in patients with hormone-refractory disease, objective response rates ranging from 19 to 69% have been reported. Preliminary clinical investigations indicate that combining estramustine phosphate with vinblastine, etoposide or paclitaxel improves objective response rates over single-agent treatment, although no survival benefit over single-agent treatment has been demonstrated to date. In comparative studies, estramustine phosphate produces similar objective response rates to conventional antineoplastic agents in patients with hormone-refractory prostate cancer. In previously untreated patients with advanced metastatic hormone-responsive prostate cancer, objective responses are achieved in approximately 80% of patients. Estramustine phosphate appears to be at least as effective as estrogen or flutamide therapy in these patients. Nausea and vomiting are the most frequently observed adverse effects of treatment with estramustine phosphate. While these symptoms are usually mild to moderate in nature, they may occasionally be more troublesome to the patient and necessitate withdrawal of treatment. Cardiovascular complications are a more serious, though less frequently encountered, adverse effect of the drug. However, these complications may be avoided by careful patient selection and prophylactic treatment measures. Unlike some other antineoplastic agents, estramustine phosphate is rarely associated with myelosuppression. In addition to producing similar objective response rates to other established agents, estramustine phosphate improves the subjective status of many patients and has been shown to reduce the intensity of pain and improve the performance status of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Absorption; Aging; Antineoplastic Agents; Clinical Trials as Topic; Drug Administration Routes; Estramustine; Humans; Male; Prostatic Neoplasms; Tissue Distribution
PubMed: 7579781
DOI: 10.2165/00002512-199507010-00006 -
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