estramustine and Carcinoma

Combinations of cytotoxic chemotherapy with estramustine phosphate (EMP), a nornitrogen mustard-estrogen conjugate, are used to treat patients with hormone-refractory prostate carcinoma (HRPC). However, thromboembolic events (TE), including deep venous thrombosis (DVT), pulmonary embolism, stroke, myocardial infarction, and arterial thrombosis, are significant toxicities of these regimens. The current study sought to establish the rate of TE and to determine risk factors for TE.. A MEDLINE-based search identified EMP-based clinical trials published in the English-language peer-reviewed literature after 1990 in which > or = 20 patients with HRPC were enrolled and TE were clearly documented. Patient characteristics and the dose of EMP given were analyzed to determine their association with the rate of TE.. Twenty-three studies, enrolling a total of 896 patients, were included in the analysis. The overall risk of TE was 0.07 (95% confidence interval [95% CI], 0.05-0.11). The risk of DVT was 0.06 (95% CI, 0.04-0.09). The risks of all other types of TE were <0.01. Using univariate logistic regression analysis, the dose of EMP administered, baseline patient age, and baseline prostate-specific antigen level were not found to be associated with the total risk of TE. The rates of total TE and DVT may be inflated because one of the analyzed studies initially had a very high rate of DVT (25%) when compared with the others.. The rate of TE in men with HRPC who are treated with EMP-based regimens is significant, but it does not appear to be related to the dose of EMP. Whether TE can be prevented with anticoagulant prophylaxis remains to be determined.

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Drug Resistance, Neoplasm; Estramustine; Humans; Male; Prostatic Neoplasms; Risk Factors; Thromboembolism; Venous Thrombosis

The national Prostatic Cancer Project has evaluated single and combination chemotherapeutic agents for the treatment of patients with advanced prostatic cancer that has been unresponsive to hormonal therapy. Although regression rates have been modest, a number of drugs have shown some efficacy and are now undergoing testing in combination. Current trials of the LH-RH agonists and the antiandrogen flutamide are in progress. These trials have demonstrated a role for chemotherapy in the treatment of the patient who has failed hormonal therapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carmustine; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Diethylstilbestrol; Doxorubicin; Estramustine; Fluorouracil; Humans; Imidazoles; Lomustine; Male; Methotrexate; Mitomycin; Mitomycins; Prednimustine; Prednisone; Procarbazine; Prostatic Neoplasms; Random Allocation; Streptozocin; Vincristine

We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer.. We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration.. There were no significant differences in the improvement rating for subjective/objective symptoms or in progression-free survival between the two groups. However, overall survival was significantly prolonged in the combination therapy group (log-rank test, P = 0.0394; generalized Wilcoxon's test, P = 0.0145). In particular, overall survival was significantly prolonged, compared to that in the endocrine monotherapy group, in patients in the combination therapy group who were less than 74 years old, those with a performance status (PS) of 1 to 3, a pretreatment prostate-specific antigen (PSA) level of more than 20 ng/ml, moderately or poorly differentiated carcinoma, or a partial response (PR) based on the PSA level 12 weeks after the start of treatment. There was no significant difference in the incidence of side effects between the combination therapy and the endocrine monotherapy groups.. A combination of EMP with endocrine therapy may be useful for initial treatment in younger patients (aged 73 or younger) and in patients at high risk of progressive prostate cancer.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Disease Progression; Disease-Free Survival; Estramustine; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostatic Neoplasms; Survival Analysis

The current study determined the efficacy and toxicity of weekly paclitaxel in combination with estramustine phosphate (EMP) in patients with androgen-independent prostate carcinoma (AIPC).. Patients with progressive AIPC received 90 mg/m2 paclitaxel by 1-hour intravenous infusion weekly for 3 weeks, followed by a 1-week treatment rest. Patients received 140 mg EMP orally 3 times daily on the day before, the day of, and the day after paclitaxel administration. Patients received 1 mg warfarin daily to prevent thromboembolism.. Sixty-six patients with progressive AIPC received treatment at 29 centers. Forty-two percent of patients had a 50% decline in prostate-specific antigen (PSA; 95% confidence interval [CI], 30-54%). For 26 patients with bidimensionally measurable disease, the objective response rate was 15% (95% CI, 1-30%). The median time to disease progression was 6.3 months, and the median time to PSA progression was 11.4 months. The median survival period was 15.6 months. Grade 3-4 toxicities were uncommon and included thromboembolism (8%), anemia (3%), neutropenia (3%), and peripheral neuropathy (2%). There was one treatment-related death.. This regimen of EMP plus weekly paclitaxel was an active and well tolerated treatment for patients with AIPC.

Topics: Aged; Aged, 80 and over; Androgens; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Drug Administration Schedule; Estramustine; Humans; Infusions, Intravenous; Male; Middle Aged; Paclitaxel; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance.. A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression.. The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Carcinoma; Combined Modality Therapy; Estramustine; Humans; Infusions, Intravenous; Male; Middle Aged; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Treatment Outcome; Vinblastine

The maximum tolerated dose (MTD) and efficacy of weekly 1-hour paclitaxel with 3 days of high dose oral estramustine were evaluated in patients with hormone-refractory prostate carcinoma.. Patients enrolled in cohorts of three received two cycles of six weekly treatments with 1 week of rest: Cohort I received paclitaxel 40 mg/m2 and estramustine 600 mg/m2, and Cohorts II-IV received paclitaxel 60 mg/m2, 75 mg/m2, or 90 mg/m2, respectively, and estramustine 900 mg/m2. Toxicity was assessed weekly, and response was measured by serum prostate specific antigen (PSA), abdominal computed tomography scans, and bone scans at Week 13.. Eighteen patients were enrolled, with 12 in Cohorts III and IV. Four patients did not complete treatment. Grade 3 toxicity included one patient with nausea and diarrhea in Cohort III and one patient each with neutropenia and edema followed by Grade 4 thromboembolism in Cohort IV. Grade 1-2 anemia or myelotoxicity were not observed; 3 patients had neuropathy, 5 patients had hair loss, and 8 patients had gastrointestinal symptoms. A decline in the serum PSA level > or = 50% occurred in none of three patients, one of three patients, four of six patients, and four of six patients in Cohorts I-IV, respectively. An intent-to-treat analysis showed responses in 9 of 18 patients (50%) in Cohorts I-IV, with 9 of 15 responders (60%) in Cohorts II-IV. Seven patients achieved declines in serum PSA levels > 75%. The median duration of PSA response was 16.7 weeks. Response was observed in one of three patients with measurable disease.. The MTD for 1-hour weekly paclitaxel was 90 mg/m2 with 3 days of 900 mg/m2 estramustine. Hematologic and neurotoxicity were reduced markedly, and gastrointestinal symptoms were ameliorated, but thromboembolic events were unaffected. PSA response rates were within the expected 60% range for these agents.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Dose-Response Relationship, Drug; Estramustine; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Prostatic Neoplasms; Treatment Outcome

A Phase II study was initiated to evaluate the effectiveness of an oral regimen of etoposide and estramustine in patients with early recurrent prostate carcinoma.. Patients with early recurrent prostate carcinoma as indicated by an increasing prostate specific antigen (PSA) level and without any evidence of metastatic disease were treated with oral etoposide 50 mg/m2/day and estramustine 15 mg/kg/day in divided doses for 21 days, followed by a 7-day rest period. Patients received a maximum of four cycles.. Eighteen patients were entered in this study. The median serum PSA was 3.1 (range, 0.3-30.3) at the time of entry into the trial. Sixteen patients were assessable for response. Serum PSA declined to undetectable levels in 13 patients with 2 additional patients meeting the criteria for partial response; the median duration of response was 8.5 months (range, 1-18 months). Most patients developed gastrointestinal, cardiac, or hematologic complications. Grade 3 toxicities included neutropenia (one patient), deep venous thrombosis (three patients), and chest pain (one patient). One patient developed acute myelogenous leukemia (French-American-British, acute myelogenous leukemia M5) 23 months after initiating the chemotherapy.. The combination of oral etoposide and oral estramustine resulted in a high rate but only a short duration of response in patients with early recurrent prostate carcinoma. The regimen was poorly tolerated, and the toxicity was significant. This regimen should not be considered standard therapy for the treatment of early recurrent prostate carcinoma, but further exploration of treatment in this setting is warranted.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Disease Progression; Disease-Free Survival; Estramustine; Etoposide; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

Nearly all cases of metastatic prostate carcinoma progress, after hormonal ablation, to a hormone refractory status. To the authors' knowledge no standard chemotherapy for patients with hormone refractory prostate carcinoma (HRPC) exists. In a prospective study, the efficacy and toxicity of an oral combination of estramustine and cyclophosphamide were evaluated.. Between March 1996 and April 1998, 32 consecutive patients (median age 74 years; range, 53-84 years) with metastatic HRPC were treated with oral estramustine (10 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 14 days every 28 days. Inclusion criteria were previous complete androgen blockade, antiandrogen withdrawal evaluation, and clinical or biochemical disease progression. Response assessment was based on a decrease > or =50% in the prostate specific antigen (PSA) level associated with improvement (or no worsening) in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and relief of bone pain (if present).. All patients were evaluable for efficacy and toxicity. PSA levels decreased by at least 50% in 14 patients (43.7%) (95% confidence interval, 26.5-60.9), remained stable in 12 patients (37.5%), and rose in 6 patients (18.8%). ECOG PS was 0 in 5 of 14 patients, improved from 1 to 0 in 7 patients, and remained unchanged in 2 patients. Bone pain, present in 8 of 14 patients, disappeared in 7 and was partially relieved in 1. The median duration of response was 30 weeks (range, 8-88+ weeks). An objective partial response was obtained in two cases. Toxicity was mild and mainly gastrointestinal (World Health Organization [WHO] Grade 1). No cases of WHO Grade 3-4 hematologic toxicity occurred.. The oral combination of estramustine and cyclophosphamide appears to be safe and effective in patients with HRPC. In responding patients its use shows a clinical benefit in terms of improvement of ECOG PS and pain control.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Chi-Square Distribution; Confidence Intervals; Cyclophosphamide; Disease Progression; Estramustine; Follow-Up Studies; Humans; Male; Middle Aged; Pain; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Safety

Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases. The drugs were first given separately, each to six patients, for five days, and then concomitantly for the same period. The bioavailabilities of the drugs were calculated on the last day of each treatment period. When clodronate was given alone, its concentrations in serum and AUC for one dose interval (6 hr) did not differ from those obtained with the drug given concomitantly with estramustine phosphate, nor did the combination of estramustine phosphate change the excretion of clodronate in urine. The serum concentrations of estramustine phosphate were elevated by about 80% when the drug was given together with clodronate. The AUC for one dose interval (12 hr) was also significantly higher for estramustine phosphate with clodronate than without clodronate. The urinary excretion of estrone, a major metabolite of estramustine phosphate, was also significantly higher after the admission with clodronate. The results suggest that clodronate increases the oral bioavailability of estramustine phosphate.

Topics: Administration, Oral; Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Analysis of Variance; Antineoplastic Agents, Hormonal; Biological Availability; Bone Neoplasms; Carcinoma; Clodronic Acid; Drug Synergism; Drug Therapy, Combination; Estramustine; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms

Topics: Antineoplastic Agents; Carcinoma; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Drug Administration Schedule; Estramustine; Europe; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms; Random Allocation

A prospective randomized trial for metastatic prostatic cancer in 220 patients who were refractory to hormone therapy was conducted by the National Prostatic Cancer Project from 1984 to 1985. As of July, 1986, the evaluation of these patients reflected no difference in response to either estramustine phosphate (Emcyt) or flutamide. Toxicities were minimal, and the observed survival and progression-free survival intervals were noteworthy in view of the overall prospects for such patients. Future studies dealing with specific quality of life issues seem to be indicated by our results.

Topics: Anilides; Carcinoma; Clinical Trials as Topic; Estramustine; Flutamide; Hematologic Diseases; Humans; Male; Nausea; Nitrogen Mustard Compounds; Prospective Studies; Prostatic Neoplasms; Random Allocation; Vomiting

From July, 1980, to June, 1983, 319 patients with newly diagnosed metastatic prostatic cancer were randomized to one of three treatment protocols: diethylstilbestrol (DES) or bilateral orchiectomy, cyclophosphamide plus 5-fluorouracil plus DES, and estramustine phosphate (Emcyt). Ninety-three per cent of 296 patients were eligible for evaluation. This report shows no difference in survival, disease-free progression time, or status regarding pain at entry. Other prognostic factors failed to reveal any difference within any of the treatment protocols.

Topics: Blood Platelets; Carcinoma; Clinical Trials as Topic; Cyclophosphamide; Diethylstilbestrol; Estramustine; Fluorouracil; Humans; Leukocytes; Male; Nitrogen Mustard Compounds; Orchiectomy; Prostatic Neoplasms; Random Allocation

In a randomized phase III trial performed by the Urological Group of the European Organization for Research on Treatment of Cancer low dose estramustine phosphate (280 mg. twice daily for 8 weeks and 140 mg. twice daily thereafter) was compared to diethylstilbestrol (1 mg. 3 times daily) in patients with stages T3 to T4, M0 or M1 prostatic cancer. Of 248 patients entered 227 were evaluable for analysis: 115 received estramustine phosphate and 112 received diethylstilbestrol. The best response of the local tumor as assessed by palpation was seen in patients receiving diethylstilbestrol. There was no significant difference between treatments for response rate of metastases, interval to local progression, distant progression, over-all survival and death of carcinoma of the prostate. Duration of survival was correlated with the assessment of local response as determined by palpation. The response of distant lesions also was correlated closely with survival. Diethylstilbestrol (1 mg. 3 times daily) was associated with a significantly worse degree of cardiovascular toxicity than estramustine phosphate. This finding was especially obvious in patients who had no history of cardiovascular disease. Gastrointestinal toxicity occurred in 25 patients treated with estramustine phosphate, including 6 in whom cessation of treatment was necessary. Further studies are required to determine the optimum dose of diethylstilbestrol and estramustine phosphate, and to establish the best form of hormonal treatment for prostatic carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Cardiovascular Diseases; Clinical Trials as Topic; Diethylstilbestrol; Estramustine; Europe; Gastrointestinal Diseases; Humans; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation

We have investigated a group of 30 patients with newly diagnosed metastatic carcinoma of the prostate who were randomly assigned to receive, as primary treatment, either diethylstilbestrol (DES) or estramustine phosphate (Emcyt). Clinical response was assessed following the guidelines of the National Prostatic Cancer Project and the Eastern Cooperative Oncology Group. Effective reduction in the levels of androgens was noted in all patients in both groups regardless of response. During the follow-up period (ranging between 2-5 years) relapses were noted despite the presence of androgen levels at or below castrate values. The most relevant endocrine observation was the detection of early elevations in serum prolactin in a majority of patients. It was noted, however, that those patients in whom hyperprolactinemia did not occur or appeared only briefly at the beginning of therapy, experienced a prolonged, symptom-free survival. Persistent hyperprolactinemia, on the other hand, carried an ominous prognosis. The differences in survival between normoprolactinemic and hyperprolactinemic groups carried statistical significance.

Topics: Carcinoma; Clinical Trials as Topic; Diethylstilbestrol; Double-Blind Method; Estramustine; Humans; Male; Nitrogen Mustard Compounds; Prolactin; Prostatic Neoplasms; Random Allocation; Testosterone

The national Prostatic Cancer Project has evaluated single and combination chemotherapeutic agents for the treatment of patients with advanced prostatic cancer that has been unresponsive to hormonal therapy. Although regression rates have been modest, a number of drugs have shown some efficacy and are now undergoing testing in combination. Current trials of the LH-RH agonists and the antiandrogen flutamide are in progress. These trials have demonstrated a role for chemotherapy in the treatment of the patient who has failed hormonal therapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carmustine; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Diethylstilbestrol; Doxorubicin; Estramustine; Fluorouracil; Humans; Imidazoles; Lomustine; Male; Methotrexate; Mitomycin; Mitomycins; Prednimustine; Prednisone; Procarbazine; Prostatic Neoplasms; Random Allocation; Streptozocin; Vincristine

Topics: Capsules; Carcinoma; Castration; Clinical Trials as Topic; Diethylstilbestrol; Double-Blind Method; Estramustine; Humans; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation; Time Factors

The antimicrotubule drug estramustine phosphate (EMP) has been shown to sensitize prostate carcinoma cells to radiation via synchronization at the G2/M phase of the cell cycle. This synchronization may also render cells more sensitive to hyperthermia, providing a rationale for multimodal treatment approaches. We have investigated the effects of EMP and hyperthermia, as well as the regulation of heat shock proteins (HSP) in the PC-3 prostatic carcinoma cell line. Cells were incubated with four doses of EMP for 48 h followed by a 1-h hyperthermia treatment ranging from 41 degrees C to 44 degrees C. Cell cycle distribution at the end of the EMP incubation was investigated by flow cytometry. Cytotoxicity was assessed by colony formation assays. HSP accumulation was investigated by Western immunoblotting. Doses of 1, 5, 10 and 15 microM EMP synchronized 27, 28, 46, and 68% of PC-3 cells at G2/M. With 5, 10 and 15 microM, a sensitizing effect of EMP was assessed at hyperthermic temperatures of 42, 43 and 44 degrees C. EMP did not alter the expression of HSP72, but substantially induced the synthesis of HSP27 in PC-3 cells. Our data show that EMP sensitizes PC-3 cells to hyperthermia induced cytotoxicity. This observation supports the rationale for multimodal treatment approaches in locally advanced prostate cancer.

Topics: Antineoplastic Agents; Carcinoma; Cell Cycle; Estramustine; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Humans; Hyperthermia, Induced; Male; Molecular Chaperones; Neoplasm Proteins; Prostatic Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay

This study was conducted to evaluate whether estramustine (estrogen mustard [EM]) is a promising alternative in the treatment of patients with epithelial ovarian carcinoma (OVCA). EM is a microtubule-associated protein (MAP) specific antimicrotubule agent with low toxicity.. The authors investigated the ability of EM to induce apoptosis and suppress colony formation of OVCA cells. Paclitaxel was used as a positive control. DNA electrophoresis and terminal deoxynucleotidyl dUTP-X nick end labeling (TUNEL) assays were used to detect internucleosomal DNA fragmentation. Flow cytometry was used to identify apoptotic cells and disturbance of the cell cycle of EM-treated OVCA cells further. Quantitation of detached cultured cells also provided a relative estimate of the apoptotic response of OVCA cells to treatment with EM. The colony formation assay was used to evaluate the effects of EM on clonogenicity.. The effects of EM on four OVCA cell lines in culture were highly similar to those of paclitaxel in causing apoptosis and inhibiting clonogenicity. DNA electrophoresis and TUNEL assays showed that EM induced internucleosomal DNA fragmentation in OVCA cells. Flow cytometry showed changes typical of apoptotic changes and cell cycle block and synchronization at the G2/M-phase. Counting of detached cells showed a log-dose response to EM treatment. The colony formation assay also showed a log-dose response suppression of OVCA cell clonogenicity after treatment with EM.. EM may be a promising candidate in the clinical treatment of patients with OVCA. The lower toxicity and MAP specific action of EM is a novel chemotherapy for OVCA.

Topics: Antineoplastic Agents, Alkylating; Apoptosis; Carcinoma; Estramustine; Female; Humans; In Situ Nick-End Labeling; Ovarian Neoplasms; Paclitaxel; Tumor Cells, Cultured; Tumor Stem Cell Assay

An estramustine-resistant human ovarian carcinoma cell line, SKEM, was generated to explore resistance mechanisms associated with this agent. Cytogenetic analysis revealed that SKEM cells have a homogeneously staining region (hsr) at chromosome 9q34. Microdissection of the hsr, followed by fluorescence in situ hybridization to SKEM and normal metaphase spreads, confirmed that the amplified region was derived from sequences from 9q34. In situ hybridization with a probe specific for ABC2, a gene located at 9q34 that encodes an ATP-binding cassette 2 (ABC2) transporter, indicated that this gene is amplified approximately 6-fold in the estramustine-resistant cells. Southern analysis confirmed that ABC2 was amplified in SKEM, and Northern analysis indicated that the ABC2 transcript was overexpressed approximately 5-fold. The ABC1 gene located at 9q22-31 was not amplified in the resistant cells, and mRNA levels of several other ABC transporter genes were unaltered. Consistent with the concept that increased ABC2 expression contributes to the resistant phenotype, we observed that the rate of efflux of dansylated estramustine was increased in SKEM compared with control cells. In addition, antisense treatment directed toward ABC2 mRNA sensitized the resistant cells to estramustine. Together, these results suggest that amplification and overexpression of ABC2 contributes to estramustine resistance and provides the first indication of a potential cellular function for this product.

Topics: Antineoplastic Agents, Hormonal; ATP-Binding Cassette Transporters; Carcinoma; Chromosomes, Human, Pair 9; Down-Regulation; Drug Resistance, Neoplasm; Estramustine; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization, Fluorescence; Oligonucleotides, Antisense; Ovarian Neoplasms; Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

The time from first diagnosis of primary multiple metastatic prostate carcinoma until progression and until death in patients less than 60 years old under two different therapeutic regimens was evaluated.. In the group with pure androgen deprivation (n = 21), the mean time until progression was 11.3 (6-55) months, the mean survival time being 21.4 (11-75) months. In the group with androgen deprivation plus cytostatic therapy (n = 10), progression was noted after 26.7 (15-77) months with a medium survival time of 26.2 (16-82) months.. The data argue in favor of changing the usual treatment strategy to combination therapy in "young' patients with primary metastatic prostatic cancer.

Topics: Adult; Androgens; Antineoplastic Agents; Bone Neoplasms; Carcinoma; Castration; Cisplatin; Combined Modality Therapy; Doxorubicin; Estramustine; Gonadotropin-Releasing Hormone; Guidelines as Topic; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; World Health Organization

The usefulness of estramustine phosphate (ECT) for preventing flare-up in goserelin acetate depot therapy for advanced prostate cancer was studied. Pretreatment with ECT 560 mg daily for 3 weeks almost completely prevented the rise in testosterone level seen in goserelin acetate depot therapy and no signs or symptoms of tumor flare were observed. Long-term ECT completely blocked the rise in luteinizing hormone and testosterone level, but ECT at this dosage was likely to cause complications. The administration of ECT 560 mg daily for 3 weeks prior to goserelin acetate depot therapy was considered sufficient to prevent tumor flare, and its effect was considered to be more marked than that of short-term treatment with antiandrogens.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Disease Progression; Drug Therapy, Combination; Estramustine; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Estramustine previously has been shown to interact with P-glycoprotein and to restore intracellular accumulation of vinblastine and paclitaxel in cells overexpressing this drug transporter. However, the ability of estramustine to potentiate the cytotoxicities of several drugs was less than that expected. To resolve this apparent discordance, the authors examined the effects of serum on the actions of estramustine.. The cytotoxicities of anticancer drugs with or without estramustine or verapamil toward MCF-7 breast carcinoma cells and a P-glycoprotein-overexpressing subline MCF-7/ADR were determined using the sulforhodamine-binding assay. The extent of intracellular accumulation of [3H]vinblastine and [3H]paclitaxel was determined for each using standard methods, and the binding of radiolabeled drugs to plasma proteins was characterized by equilibrium dialysis.. Without serum, the sensitivities of MCF-7/ADR cells to several P-glycoprotein-transported drugs were increased by estramustine and verapamil. Conversely, when the cells were treated with a 10% serum, the cytotoxicities of these drugs were increased by verapamil, but not by estramustine. Without serum, intracellular accumulation of [3H]vinblastine and [3H]paclitaxel by MCF-7/ADR cells was increased markedly by verapamil and estramustine; however, serum suppressed the effects of estramustine much more strongly than those of verapamil. Equilibrium dialysis experiments demonstrated that [3H]estramustine binds to plasma proteins, predominantly albumin, whereas [3H]paclitaxel binds to albumin and alpha 1-acid-glycoprotein, and [3H]vinblastine binds predominantly to alpha 1-acid-glycoprotein.. Although estramustine can bind to P-glycoprotein, its effectiveness as a reversing agent in vivo likely is limited by binding to plasma proteins.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood Proteins; Breast Neoplasms; Carcinoma; Dialysis; Drug Resistance, Multiple; Estramustine; Gene Expression Regulation, Neoplastic; Humans; Orosomucoid; Paclitaxel; Protein Binding; Serum Albumin; Tritium; Tumor Cells, Cultured; Verapamil; Vinblastine

This report provides new morphological insights, based on diagnostic methods, into metastases to the bone in prostate cancer patients. Lumbar CT examination is available to evaluate whether metastases are truly present or not, especially in aged patients with positive bone scans. The evaluation of response is clearer on CT. Furthermore, CT is useful not only in estimating the presence of metastases, CT also provides definite details on the extent of the metastatic condition.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Carcinoma; Chlormadinone Acetate; Diagnosis, Differential; Estramustine; False Positive Reactions; Follow-Up Studies; Humans; Male; Middle Aged; Osteolysis; Prostatic Neoplasms; Radionuclide Imaging; Spinal Diseases; Spinal Neoplasms; Tomography, X-Ray Computed

Estramustine (EM) and taxol, two antimicrotubule agents with distinct and apparently opposing mechanisms of action, were found to be effective in combination in the preclinical treatment of EM-resistant and sensitive, wild-type human prostatic carcinoma cell lines. Estramustine combined with 1 nM taxol (concentration 100-fold less than that measured in plasma of patients treated with taxol) produced greater than additive effects on the inhibition of cell survival of both wild-type and EM-resistant cells. When taxol was used with another microtubule-destabilizing drug, vinblastine, no significantly increased cytotoxicity was observed. Other effects on wild-type and EM-resistant cells produced by the combination of EM and taxol included (a) an increased proportion of the cells in the S phase of the cell cycle; (b) no mitotic block; and (c) an increase in the percentage of micronucleated cells from a control value of less than 1% to greater than 20% after drug treatment. Immunofluorescent microscopic analysis of the effect of this drug combination on the mitotic spindle apparatus revealed specific examples of aberrant mitotic figures, including multiple asters, cells with two distinct spindles, and tripolar spindles able to traverse mitosis and complete cytokinesis. These data provide supportive preclinical evidence for the potential development of an EM/taxol combination clinical regimen either for prostate or other cancers.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cell Cycle; Drug Screening Assays, Antitumor; Estramustine; Flow Cytometry; Humans; Male; Micronucleus Tests; Microtubules; Paclitaxel; Prostatic Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay

The usefulness of serum acid phosphatase (SAP) in monitoring patients with advanced prostate carcinoma has been questioned. We reviewed a series of 59 patients with stage D2 prostate carcinoma. All patients had extended follow-up through at least one clinical relapse, or death. Responses to a variety of therapies were characterized as absent, subjective, or objective. All patients with an elevated pre-treatment SAP that fell to normal following therapy had prolonged survivals and improved prognoses. Conversely, all patients with an elevated SAP which did not normalize following therapy had poorer survivals. Among 36 objective responses to therapy, the SAP was elevated prior to or simultaneous with disease progression in 33 (93% sensitivity). In each ease where the pretreatment SAP normalized following therapy, any subsequent elevation in SAP above normal was always associated with clinical evidence of disease progression (100% specificity). Changes in SAP following therapy correlate well with both disease regression and disease progression in patients with advanced prostatic carcinoma.

Topics: Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Cyclophosphamide; Estramustine; Estrogens; Flutamide; Follow-Up Studies; Humans; Male; Neoplasm Proteins; Neoplasm Staging; Orchiectomy; Predictive Value of Tests; Prostatic Neoplasms; Treatment Outcome

Estramustine is one of the main metabolites of estramustine phosphate (EstracytR), a drug used in the treatment of advanced prostatic cancer. In the present study the hormone independent human prostatic carcinoma cell line DU 145 implanted subcutaneously in nude mice (NMRI) was used to investigate the mode of action of estramustine in vivo. Metaphase arrest was found in mice treated with estramustine intraperitoneally, 200 and 400 micrograms daily for 2 weeks, 5 days a week. A significant dose dependent decrease in the number of anaphase figures was found. A 7 to 8 fold increase in the number of abnormal metaphases, i.e., highly contracted and unaligned chromosomes, was found. Uptake and retention of 3H-estramustine was found in tumour tissue. No increase in the mitotic index or the number of abnormal metaphases was found in animals treated with polyestradiol phosphate (EstradurinR). This is the first time evidence has been presented demonstrating the anti-mitotic effect of estramustine in vivo.

Topics: Animals; Carcinoma; Estramustine; Humans; Male; Mice; Mice, Nude; Mitotic Index; Neoplasm Transplantation; Prostatic Neoplasms; Tumor Cells, Cultured

The expression of the proliferation-associated antigen Ki-67 was studied in human prostatic cancer. The antigen was analyzed with an immuno-histochemical technique in TUR specimens. A correlation was seen between Ki-67 positivity and differentiation grade. All TUR specimens (15/15) with poorly differentiated carcinomas expressed the antigen. Moderately differentiated carcinomas constituted an intermediate group and slightly less than half of the cancers (12/27) were positive for the antigen. Only one of the highly differentiated carcinomas (1/12) expressed the antigen. All TUR specimens from patients with benign prostatic hyperplasia (8/8) were negative. The effect on Ki-67 positivity was also investigated in a human prostatic cancer heterotransplanted to nude mice and subjected to ionizing irradiation with or without concomitant estramustine treatment. The antigen expression was compared with that seen in tumour tissues from untreated mice and from mice treated with estramustine alone. A pronounced effect was seen in the combination treatment group with an approximately 50% reduction of the Ki-67 positive cells. The results are discussed in relation to prognosis and follow-up after radiation therapy and the possible use of estramustine in combination with radiation therapy.

Topics: Animals; Carcinoma; Combined Modality Therapy; Estramustine; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Male; Mice; Mice, Nude; Neoplasm Transplantation; Nuclear Proteins; Prostatic Neoplasms; Tumor Cells, Cultured

In this retrospective study, 71 patients with secondary hormone-refractory prostatic carcinomas were treated with estramustine phosphate (EMP), at three different dosages (280, 560, 840 mg orally). All patients were completely followed up until cancer-induced death. In 12 cases of further progression polychemotherapy was administered. As this was not a randomized study, an analysis of statistical significance was not performed. The higher dosages of EMP caused an extended progression-free interval accompanied by an equally considerable alleviation of carcinoma-induced pain. The overall survival time was not influenced by subsequent polychemotherapy. An elevation of liver function parameters was observed in 5 patients. One of these patients died of toxic liver damage, possibly therapy-related, on the basis of a preexisting cirrhosis. Cardiovascular side effects were not observed. With regard to survival time, the positioning of polychemotherapy as a third-line treatment for prostatic cancer should be examined critically. Before administration of high-dose EMP, it is mandatory to control liver functions carefully.

Topics: Aged; Carcinoma; Estramustine; Humans; Liver Function Tests; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Retrospective Studies; Time Factors

In this paper the authors review the completed and current EORTC Genitourinary Group trials for metastatic carcinoma of the prostate. In terms of time to progression and length of survival, there is no significant difference between any of the effective endocrine treatments that have been studied. The statistical analysis of the different variables used in trials 30,761 and 30,762 determines three risk groups of patients. There is no need for very special laboratory investigations to establish a prognosis. Orchiectomy is the cheapest and safest endocrine treatment in metastatic carcinoma of the prostate.

Topics: Androgen Antagonists; Carcinoma; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Europe; Gonadotropin-Releasing Hormone; Hormones; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

Prostata cancer is one of the most dangerous tumours occurring in the older man. No general accepted therapy has existed up to now. In this study we were engaged on the pharmacokinetics of fosfestrol (Honvan) after oral administration. Its active principle is E-diethylstilbestrol (E-DES), the main metabolite. 250-1600 ng/ml E-DES are measurable after 60-110 min in the plasma of 11 patients suffering from metastatic prostata cancer who have been administered 360 mg fosfestrol orally. This range is equivalent to E-DES concentrations in plasma of 1-4 x 10(-6) mol/l. Thus that E-DES concentration range (5 x 10(-6) mol/l) is nearly attained for a short time to the concentration which hinders the mitosis of human breast cancer cells. Surprisingly similar but not higher concentration - time courses may be measured after a bolus infusion of 360 mg fosfestrol (lasting 45 min). Furthermore, E-DES-glucuronide, E-DES-sulphate and the mixed E-DES-glucuronide-sulphate could be observed in plasma after oral administration. In spite of the high sensitivity of the analytical method (limit of detection for fosfestrol 0.1 micrograms/ml and for E-DES and its mono-conjugates 2-5 ng/ml) neither fosfestrol nor E-DES-monophosphate are detectable in plasma due to the biotransformation of fosfestrol, which is already metabolized by the enzymes of the gut wall. Both phosphates only exist in plasma after intravenous infusion. Further investigations are linked with the question if phase II-conjugates of E-DES can eventually be prodrugs delivering E-DES by cleavage of the ester bonds.

Topics: Administration, Oral; Aged; Androgen Antagonists; Antineoplastic Agents; Biological Availability; Biotransformation; Carcinoma; Chemical Phenomena; Chemistry; Diethylstilbestrol; Estramustine; Estrogens; Humans; Ketoconazole; Male; Middle Aged; Neoplasm Metastasis; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Protein Binding

Plasma and tumour concentrations of estramustine, estromustine, estradiol and estrone, the major metabolites of estramustine phosphate (estracyt), were determined in patients with prostatic carcinoma treated between one and nine years with repeated oral doses of estracyt (560 to 840 mg./day). The last dose was given 12 to 16 hours before sampling. The binding of radioactive estramustine and estromustine was determined in the tumour tissue to examine the possible role of estramustine-binding protein for the accumulation of these metabolites into the tumour. Comparison was made with benign prostate hyperplastic tissue from untreated patients. Estromustine was the main metabolite in plasma as well as in the tumour (range 235 to 450 and 205 to 485 ng./gm., respectively), whereas estramustine (20 to 45; 95 to 370), estrone (62 to 140; 63 to 160) and estradiol (8 to 15; 7 to 36) were found in lower concentrations. Interestingly the concentration of estramustine was as an average six times higher in the tumour than in plasma contrasting with the other metabolites which were present in equal amounts of the two localities. Binding of 3H-estramustine and 3H-estromustine was two to three times higher in the tumour than in benign hyperplastic tissue and negligible in plasma samples. The present study is the first where substantial amounts of cytotoxically active estramustine and estromustine are demonstrated in tumour tissue from estracyt treated patients. Our findings suggest a mechanism for selective uptake of these metabolites in prostatic cancer (estramustine-binding protein). The uptake and binding of estramustine and estromustine in the tumour may account for the clinical effects of estracyt in prostatic carcinoma.

Topics: Aged; Carcinoma; Carrier Proteins; Estradiol; Estramustine; Estrone; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostate; Prostatic Neoplasms; Prostatic Secretory Proteins

Estramustine (EM) is a conjugate of estradiol and nor-nitrogen mustard (nor-HN2), which is effective in the treatment of prostate cancer. We have compared the effect of EM with that of the known microtubule inhibitor vinblastine (VLB) on the following functions of malignant MO4 mouse cells and of DU-145 human prostate cancer cells in vitro: directional migration, invasion; and the organization and the assembly/disassembly equilibrium of microtubule complexes. The circular area covered by cells migrating from an aggregate explanted on a solid substrate was taken as an index of directional migration. Invasion was studied through confrontation of MO4 or DU-145 cells with fragments of embryonic chick heart in organ culture. Microtubules were investigated immunocytochemically and through immunodetection on protein blots. VLB and EM inhibited directional migration and invasion of MO4 and DU-145 cells in a dose-dependent manner; equimolar combinations of estradiol plus nor-nitrogen mustard did not mimic these effects. At anti-invasive concentrations VLB led to partial disassembly of microtubule complexes, whereas EM resulted in an abnormal pattern of microtubule complexes without alteration of the overall assembly/disassembly equilibrium. Combined treatment with VLB and EM resulted in an enhanced VLB effect, namely complete disassembly. In all tests DU-145 cells were more sensitive to both VLB and EM than were MO4 cells, and the effects were less reversible. The present experiments showed that EM shares an anti-invasive activity with other microtubule inhibitors.

Topics: Animals; Carcinoma; Cell Movement; Estradiol; Estramustine; Humans; Male; Mechlorethamine; Mice; Microtubules; Nitrogen Mustard Compounds; Organ Culture Techniques; Prostatic Neoplasms; Tubulin; Vinblastine

Topics: Animals; Buserelin; Carcinoma; Dogs; Estramustine; Gonadotropin-Releasing Hormone; Humans; Japan; Male; Orchiectomy; Prostate; Prostatic Neoplasms; Testosterone; Ultrasonography

The treatment of prostatic carcinoma with estrogens is associated with an increased risk of cardiovascular as well as thromboembolic complications. In the present study, patients harboring highly or moderately differentiated prostatic carcinoma without signs of metastases were treated with either polyestradiolphosphate + etinylestradiol, estramustine phosphate or given no treatment. Subsequently, these patients were investigated regarding factors (platelet aggregation, plasma and platelet phospholipid composition and lipoprotein patterns) that might contribute to increased thrombogenesis and cardiovascular risk. The results indicate the presence of increased in vitro platelet aggregation in patients treated with polyestradiolphosphate + etinylestradiol compared to those treated with estramustine phosphate or given no treatment. A possible relationship between the availability of arachidonic acid in platelet membrane phospholipids and in vitro platelet aggregation is suggested. On the other hand the alterations in plasma lipoproteins observed during treatment are generally considered positive from an atherogenic point of view and do not seem relevant to the elevated incidence of cardiovascular disease in these patients.

Topics: Aged; Apolipoproteins; Carcinoma; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Drug Therapy, Combination; Estradiol; Estradiol Congeners; Estramustine; Ethinyl Estradiol; Fatty Acids; Humans; Lipoproteins; Male; Nitrogen Mustard Compounds; Platelet Aggregation; Prostatic Neoplasms; Risk; Thromboembolism; Triglycerides

Estramustine phosphate, a combination steroid and alkylating agent, has been used for treatment of cancer of the prostate since 1969. We treated 32 patients with Stages C and D prostate cancer with this compound. Using the National Prostatic Cancer Project criteria of response, no patient achieved complete or partial objective response. Sixty-two per cent of the patients without prior hormonal manipulation and 12 per cent of those who were progressing following hormonal therapy met the criteria for a stable response. Both Stage C patients, 50 per cent of D1 and 28 per cent of D2 patients achieved disease stabilization for a mean duration of 14.8 months. There was no correlation between tumor grade and response to treatment. Fifty per cent of the patients whose elevated acid phosphatase declined remain stable, whereas 80 per cent in whom the acid phosphatase did not decline have progressed. Estramustine is effective in patients without prior hormonal manipulation. In those refractory to hormones, the prognosis is poor yet data exist to support the superiority of estramustine phosphate over conventional therapy.

Topics: Aged; Carcinoma; Estramustine; Hormones; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms

In growth proliferation experiments on two human prostatic carcinoma cell lines, DU 145 cells were found to be more sensitive to the cytotoxic effect of estramustine and nor-nitrogen mustard than PC-3 cells. Estramustine was, however, much more cytotoxic in both cell lines than nor-nitrogen mustard. Cytogenetic experiments revealed that estramustine produced a drastic increase of the mitotic index in both these cell lines. This increase could be accounted for by the arrest of cells in their first treatment-metaphase. The arrested metaphases exhibited all the characteristics commonly found for stathmokinetic agents such as colchicine and vinca-analogues. No mitotic arrest was found for nor-nitrogen mustard but chromosomal aberrations were found at toxic concentrations. Estradiol exhibited minimal toxicity and caused no mitotic arrest in these cell lines. The mitotic arrest induced by estramustine was found to be reversible on removal of the drug.

Topics: Carcinoma; Cell Line; Cell Survival; Cells, Cultured; Drug Evaluation, Preclinical; Estramustine; Humans; In Vitro Techniques; Karyotyping; Male; Mitosis; Nitrogen Mustard Compounds; Prostatic Neoplasms; Time Factors

Estramustine at concentrations ranging from 3-40 x 10(-6) M inhibited the cell growth and clonogenic survival of a human prostatic carcinoma cell line (DU 145). This cell line was found to be unresponsive to estradiol and testosterone at concentrations ranging from 10(-9) M to 5 x 10(-5) M. Metabolism studies with estramustine showed that only a few per cent of the ester linkage was cleaved during the exposure period. This small amount of metabolism could possibly lead to the release of nor-nitrogen mustard, which was however found not to be as inhibitory as estramustine in this cell line. The results indicate that estramustine per se causes the cell death of hormone unresponsive human prostatic carcinoma cells in cell culture.

Topics: Carcinoma; Cell Line; Cell Survival; Cells, Cultured; Estradiol; Estramustine; Humans; In Vitro Techniques; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Testosterone

Plasma concentrations of estramustine phosphate and its major metabolites were measured in patients with prostatic carcinoma treated with increasing oral doses, 70-650 mg/day, of estramustine phosphate (Estracyt). Parent drug and estradiol were measured by radioimmunoassay, and estramustine and its estrone analogue (Leo 271) utilizing gas chromatography. The concentrations of estramustine phosphate and estramustine were below or close to the limits of the methods. A linear correlation was found between the daily dose of estramustine phosphate, and plasma concentrations of Leo 271-the main metabolite-and estradiol, which suggests that no capacity limiting processes are involved in the pharmacokinetics of estramustine phosphate in man. Plasma was also analyzed during prolonged treatment with 560 mg/day. The metabolite pattern was not changed by two to three years of estramustine phosphate treatment.

Topics: Administration, Oral; Aged; Carcinoma; Estradiol; Estramustine; Estrone; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Time Factors

40 patients with inoperable, histologically proved carcinoma of the prostate were treated with estramustine phosphate. 35 patients had progressive, symptomatic, metastatic disease unresponsive to conventional oestrogens and/or castration Estramustine phosphate was given intravenously initially at a dose of 150 mg/day increasing to 300 mg/day. After 3 weeks or more oral therapy was substituted in 23 patients at a dose of 560 mg/day. Of 23 evaluable patients given the drug by both routes, 17 died after a mean treatment period of 12.5 months and 6 are alive and well after a mean treatment period of 27.7 months. The cause of death in 2 patients was probably, and in a third certainly, due to myocardial infarction. The other 31 deaths were due to carcinoma of the prostate. 18 patients showed transient toxic side-effects. No haematological abnormalities were found during treatment. An attempt at active treatment with estramustine phosphate in patients with prostatic cancer is justified when the disease is resistant to treatment with conventional oestrogens.

Topics: Aged; Carcinoma; Estramustine; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms

40 patients with prostatic carcinoma were treated with parenteral and/or oral Estracyt (estramustine phosphate) until 55 months. Metastases were present in 37 patients (stage D). 35 of the 40 patients developed metastases in spite of estrogen therapy and/or orchidectomy. Diminution of metastasic bone pain as well as improvement of hydroureteronephrosis was frequently observed. Paraplegia secondary to metastatic disease improved in 1 case for 6 months. Side effects were relatively rare and were mainly gastrointestinal. A possible hepatotoxic action of the compound has been pointed out previously. On the basis of our studies Estracyt is recommended in the treatment of primary estrogen resistent prostatic carcinoma and in metastatic carcinoma of the prostate not responding to conventional antiandrogenic therapy anymore.

Topics: Administration, Oral; Aged; Bone Neoplasms; Carcinoma; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; Estramustine; Estrogens; Humans; Injections, Intravenous; Long-Term Care; Male; Middle Aged; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neoplasms