Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Estramustine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1999

Daily oral estramustine and intermittent intravenous docetaxel (Taxotere) as chemotherapeutic treatment for metastatic, hormone-refractory prostate cancer.

As part of an extensive search of synergistic combinations of agents that demonstrate cytotoxic activity in tissue culture against prostate cancer cell lines, we have identified estramustine phosphate and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as active. Patients with hormone-refractory metastatic prostate cancer with good performance status were entered onto a phase I trial of this combination. Estramustine phosphate was given on a daily oral dosing schedule of 14 mg/kg; docetaxel was administered intravenously over 1 hour every 3 weeks. Prophylactic corticosteroids were administered to minimize taxane side effects. Four dose levels of docetaxel were studied: 40, 60, 70, and 80 mg/m2. Actual weight was used for dosing calculations. An intermittent docetaxel dose of 70 mg/m2 with estramustine phosphate at 12 mg/kg was determined to be a phase II dose and to allow repetitive dosing. Eight additional patients were entered at this dose level of docetaxel. In all patients, the limiting side effects were fatigue and leukopenia. Thromboembolic events also were seen in 16% of patients. In the first 17 patients treated in the phase I aspect of the study, the biochemical response rate was 82%, demonstrating greater than a 50% decline in prostate-specific antigen. Twenty-four percent had normalization of prostate-specific antigen. These early studies indicate that the combination of estramustine and docetaxel has activity in this population of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

A Phase I/II study of weekly paclitaxel and 3 days of high dose oral estramustine in patients with hormone-refractory prostate carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Administration, Oral↗
PubMedDate not supplied

Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients.

Neuroendocrine (NE) differentiation in prostate cancer (PC) has attracted much attention since it has been shown to be associated with androgen independence and bad prognoses. In this study 34 patients with hormone refractory prostate cancer and elevated Chromogranin A (CgA) serum values were treated with estramustine for 15 months. The results were evaluated by analyzing clinical data and the serially measured total PSA and Chromogranin A serotest concentration, as well as bone scan recordings. In responders to therapy a sharp decline in CgA level was recorded as well as a slight decrease in the number of metastatic lesions in the bone. However, in 6- and 12-month nonresponders, supranormal serum CgA concentrations were measured (mean 305 +/- 122 ng/ml/ and 284 +/- 101 ng/ml, respectively). Statistical significance was found between neither of these groups (p > 0.05). Mean bone lesions data were practically identical in nonresponding groups (9.6 and 9.5) but were much lower in the respective responders (4.9 and 4.1). Twelve patients were found to be nonresponders 3 months after therapy initiation (12 out of 34, 35.3%). From the remaining 22 studied subjects a positive response patients continued in 17 patients during the next 3 months or overall in a six-month period (17 out of 34, 50%, or 17 out of 22, 77.3% from 3-month responders). After 9 months of therapy, 15 responding, patients were found (15 out of 34, 44.1%, or 15 out of 17, 88.2% from 6-month responders) while, after a full year of estramustine administration, 8 patients responded to therapy (8 out of 34, 23.5%, or 8 out of 15, 53.3% from responders after 9 months of treatment). Finally, after 15 months of treatment, only 3 responding patients found (3 out of 34, 8.8% or 3 out of 8, 37.5% from responders after 12 months of treatment). Mean response periods after 12 and 15 months of estramustine treatment were 5.5 and 5.7 months, respectively. In conclusion, the reported results indicate a 12-15 month responding period for estramustine therapy in patients with a slight initial elevation in CgA serotest (up to 150 ng/ml) and less than 10 metastatic osseous lesions. Thus, serum CgA assessment has definitely found a role in monitoring PC patients with NE positive stage D3 disease. This specially holds true as the population of aged men is rapidly increasing, posing a great challenge to urologists and oncologists in treating difficult-to-manage hormone-independent prostatic carcinoma.

Administration, Oral↗
PubMed1992

Molecular conformation of estramustine and two analogues.

The crystal and molecular structures of estramustine and two of its analogues have been determined by X-ray crystallographic techniques (a total of three different compounds). The compounds studied are estramustine [1,3,5(10)-estratriene-3,17 beta-diol-3-N,N-bis(2'- chloroethyl)carbamate] and its monohydrate, estromustine [17-oxo-1,3,5(10)-estratriene-3-yl-N,N-bis(2'-chloroethyl)carbamate], and 17-oxo-5-androsten-3 beta-yl-N,N-bis(2'-chloroethyl)carbamate. Three views of estramustine were obtained from the study of its two crystal forms. The main structural features found are as follows: (a) the geometries of the steroid moieties are closely similar to those of the parent steroids, (b) the bonds around the nitrogen atom of the nitrogen mustard grouping lie approximately in a plane in each structure, (c) the plane through the carbon atoms of the steroid A-ring lies approximately perpendicular to the plane through the carbamate atoms in each structure, (d) the carbonyl C-O of the carbamate points to the alpha side of the steroid moiety in each structure, and (e) one chlorine atom of the nitrogen mustard grouping makes a close contact [3.13 A], in each structure, to the nitrogen atom. Hydrogen bonding to the carbamate appears to occur from the alpha side of the steroid; there is no hydrogen bonding to the nitrogen atom of the carbamate group. These structural data provide some steric explanations for the resistance of the carbamate to enzymatic hydrolysis. The long in vivo half-life of the intact estramustine molecule is a result of this stability. This is responsible for the absence of alkylating ability and the propensity of the drug to bind microtubule-associated proteins and express an antimitotic mechanism of action.

Estramustine↗
PubMed2005

A phase I study of estramustine, weekly docetaxel, and carboplatin chemotherapy in patients with hormone-refractory prostate cancer.

PURPOSE: To define the maximal tolerated dose, safety, and efficacy of docetaxel, carboplatin, and estramustine in patients with hormone-refractory prostate cancer (HRPC). METHODS: Patients with HRPC received docetaxel for 3 weeks, followed by a rest week. Docetaxel (20, 25, 30, 36, or 43 mg/m2) was given on days 2, 9, and 16 of a 28-day cycle. Patients also received estramustine (140 mg p.o. three times daily on days 1-5, 8-12, and 15-19) and carboplatin [area under the curve, AUC (5) or (6) on day 2]. RESULTS: Thirty patients were treated. Five patients received carboplatin [AUC (6)] but experienced delayed thrombocytopenia. After a protocol amendment, 25 subsequent patients received carboplatin [AUC (5)]. Median age was 64 years. Median prostate-specific antigen (PSA) was 117 ng/mL. Fifty-three percent received prior ketoconazole and 10% had mitoxantrone. No dose-limiting toxicities were noted. Although maximal tolerated dose was not reached, docetaxel dose escalation was stopped at 43 mg/m2. Significant myelosuppression was not seen until the highest dose level, when seven and four patients experienced grade 3 and 4 toxicities, respectively. Among all patients, PSA declines of > or =50% occurred in 63%. At the recommended phase II dose, PSA declines of > or =50% occurred in 75% (95% confidence interval, 43-95). Four of 14 (29%) patients with measurable disease had partial responses. Median survival was 14.6 months. CONCLUSIONS: Estramustine, docetaxel, and carboplatin are well tolerated and active in HRPC. Myelosuppression is the primary toxicity. The recommended phase II dose of docetaxel is 43 mg/m2 combined with estramustine and carboplatin. PSA declines were seen at every dose level.

Aged↗
PubMedDate not supplied

Effects of estramustine and its constituents on human malignant glioma cells.

Estramustine, a conjugate of estradiol-17 beta and nor-nitrogen mustard currently used in prostatic cancer, was found to exert a dose-dependent antiproliferative effect on the human malignant glioma cell lines U-251 MG and U-105 MG. At equimolar concentrations the inhibitory effects of the estramustine complex were clearly more pronounced than those of estradiol and nor-nitrogen mustard given alone or in combination. Flow cytometric analyses support the concept that estramustine cytotoxicity is mediated via separate mechanisms. The intact estramustine complex may be important for effects related to microtubule function which add to the cytotoxic potential of the alkylating component.

Cell Cycle↗
PubMed1990

[Clinical evaluation of estramustine phosphate in the treatment of patients with advanced breast cancers].

Estramustine phosphate, an anti-prostatic cancer agent, was investigated on eleven patients to evaluate the efficacy in a treatment of advanced breast cancers. The daily dose of medication was 840 mg. According to criteria of Japan Society for Cancer Therapy, none was assessed as CR, three as PR, four as NC and PD. The response rate was 27.3%. There was no differences in response rates among estrogen receptor status. A favourable response was observed in postmenopausal patients but no response in premenopausal, as well as a good response in lesions of soft tissue and lung, a poor response in lesions of liver and bone. As to toxicity of estramustine phosphate, gastrointestinal disorders such as nausea, vomiting and diarrhea were noted frequently during the treatment, and a long term administration was not able to perform in premenopausal patients because of vaginal bleeding and discharge, and pain in breast. The estramustine phosphate therapy for advanced breast cancers was regarded as one of modalities for a treatment of postmenopausal patients as a second line therapy. This is the first report in Japan discussing the efficacy of estramustine phosphate for a treatment of breast cancer.

Administration, Oral↗
PubMedDate not supplied

Uptake and metabolism of estramustine in the Dunning R3327H tumour.

A time-dependent plasma, tumour cell and nuclear uptake was found after intraperitoneal 3H-estramustine administration, in rats bearing the Dunning H tumour. Uptake of the drug into tumour cells had not reached a maximum after 4 h, whereas no real change was seen in the nuclear fraction after 2 h. Binding to the nuclear protein matrix of Dunning H tumour cells of 3H-estramustine was also found (2.46 pmol/g protein). High performance liquid chromatography demonstrated the existence of estramustine, its oxidized metabolite estromustine, estradiol and estrone in the plasma and the tumour after intravenous administration of 100 microCi 3H-estramustine.

Animals↗
PubMed1983

Cytotoxicity of estramustine, a steroid-nitrogen mustard derivative, through non-DNA targets.

Estramustine is cytotoxic in HeLa and Walker 256 carcinoma cells (with or without acquired resistance to nitrogen mustards) at concentrations equivalent to other alkylating agents. Even at lethal estramustine levels, no damage to DNA occurs. Instead, a disproportionately high amount of intact estramustine binds hydrophobically to the structural proteins of the nucleus, the nuclear matrix. In HeLa cells, estradiol receptors are absent, and estradiol per se is not toxic. Thus, estramustine has a mechanism of action distinct from that of steroids and alkylating agents and may induce cytotoxicity through interactions with the proteins of the nuclear matrix.

Animals↗
PubMed1978

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9 percent of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Drug Therapy, Combination↗
PubMed1997

Response to estramustine phosphate and paclitaxel in patients with advanced breast cancer: a phase I study.

Estramustine phosphate (EMP) is thought to form a chemical link between estradiol and non-nitrogen mustard. An estramustine-binding protein has been isolated in prostate, breast, and brain cancers as well as in malignant melanoma cells. Estramustine phosphate's ability to bind to microtubular-associated proteins and to interfere with mdr-mediated drug efflux are thought to result in its enhancement of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) activity in cell lines and in its ability to affect hormone-resistant prostate cancer. This phase I study administered combined paclitaxel and EMP to 25 women with ovarian, breast, and other tumors and assessed efficacy and toxicity. Estramustine phosphate was administered at two dose levels, 900 or 1,200 mg/m2 daily on days 1, 2, and 3 in 3-week cycles. On day 3, paclitaxel (150, 180, 210, or 225 mg/m2) was given concomitantly by 3-hour infusion. Therapeutic effects were noted in all patients. Partial responses were noted in three of eight patients with breast cancer who had failed to improve on paclitaxel alone. Three other patients experienced prolonged stable disease. Only moderate toxicities were noted until EMP levels of 1,200 mg/m2 were reached. At these dose levels, gastrointestinal toxicities became more prominent. The addition of EMP to paclitaxel allowed patients to receive paclitaxel for longer periods, and may have enhanced the therapeutic effects of paclitaxel. If so, the mechanisms of such enhancement warrant investigation. The two drugs may work on different aspects of microtubular function, for example, or may reduce efflux of paclitaxel in P-glycoprotein overexpressed tumors.

Adult↗
PubMed1997

Paclitaxel, estramustine, and etoposide in the treatment of hormone-refractory prostate cancer.

We previously developed a novel and effective therapy for hormone-refractory prostate cancer using the agents estramustine and etoposide. Although neither of these agents alone is effective in the treatment of advanced, hormone-refractory prostate cancer, we predicted their activity when used in combination based on preclinical assays, and then demonstrated their effectiveness in a phase I-II clinical trial, where they were shown to produce a 50% complete and partial response rate in patients with bidimensionally measurable disease. In preclinical studies, we had demonstrated that estramustine and etoposide interact with the nuclear matrix, which is the site of DNA replication. Expanding these investigations, we determined that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a microtubule inhibitor, interacts with estramustine and etoposide, and the combination of these three agents had significant preclinical activity against androgen-independent prostate cancer cells. These studies led us to conduct a phase II clinical trial of paclitaxel, estramustine, and etoposide in patients with hormone-refractory prostate cancer. Preliminary results demonstrate that this is an active regimen, with 57% of patients demonstrating a response to therapy as measured by a decrease in pretreatment prostate-specific antigen levels of greater than 50%.

Adenocarcinoma↗
PubMed1989

Proteolytic cleavage of high-molecular-weight microtubule-associated proteins by the prostatic estramustine-binding protein.

The rat prostatic estramustine-binding protein was found to inhibit assembly of microtubules in a concentration-dependent manner. The inhibition was caused by a proteolytic cleavage of the high-molecular-weight microtubule associated proteins (MAPs), as judged by sodium dodecyl sulfate-gel electrophoresis. A proteolytic fragment with a molecular weight of 199 kDa appeared, which remained bound to the assembled microtubules. Fragments of lower molecular weights (170, 149 kDa) were also found, but they did not bind to the assembled microtubules. Fragments with identical molecular weights were also found after incubation of purified MAP2 with the estramustine-binding protein, indicating that the fragments derive from MAP2. No proteolysis of tubulin, albumin, or casein was found. The estramustine-binding protein was found to be a Zn2+-dependent protease; it was inhibited by EDTA and reactivated by addition of 1 mM Zn2+. Its proteolytic activity was not affected by binding of the antimitotic drug estramustine.

Animals↗
PubMed2001

Chemotherapy in patients with prostate specific antigen-only disease after primary therapy for prostate carcinoma: a phase II trial of oral estramustine and oral etoposide.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Administration, Oral↗
PubMed2003

Phase II trial of paclitaxel, estramustine, etoposide, and carboplatin in the treatment of patients with hormone-refractory prostate carcinoma.

BACKGROUND: Preclinical data suggest that the combination of intravenous (i.v.) paclitaxel, carboplatin, oral etoposide, and oral estramustine (TEEC) has significant activity in patients with advanced, hormone-refractory prostate carcinoma. The authors conducted this clinical trial to evaluate the addition of carboplatin to the three-drug combination of paclitaxel, estramustine, and etoposide (TEE). METHODS: Twenty patients with carcinoma of the prostate that was progressing despite hormone therapy were enrolled on this Phase II trial. Patients were treated with oral estramustine, 280 mg three times daily, and oral etoposide, 50 mg/m2, once daily on Days 1-7, with i.v. paclitaxel, 135 mg/m2, over 1 hour followed by carboplatin (area under the curve, 5) on Day 2 of each 21-day treatment cycle. Patients were evaluated for response after three cycles, and three additional cycles were given to responding or stable patients. RESULTS: Nineteen patients were evaluable for response, and 12 patients had measurable disease at baseline. The measurable response rate was 58% (7 of 12 patients; 95% confidence interval [95% CI], 28-85%), and all of those were partial responses. Eleven patients had decreases >50% from their baseline prostate specific antigen levels during therapy, for a response rate of 58% (95% CI, 34-80%) by this criterion. The median time to disease progression was 5.5 months, with a median survival of 14.2 months. Major toxicities included Grade (according to version 2 of the National Cancer Institute Common Toxicity Criteria) 4 neutropenia in 4 patients, Grade 4 thrombocytopenia in 4 patients, and anemia > or = Grade 3 in 4 patients. One patient had a deep vein thrombosis. CONCLUSIONS: The combination of TEEC was active in patients with hormone-refractory prostate carcinoma. The regimen was tolerable, with primarily hematologic toxicity. The addition of carboplatin to TEE did not appear to add to the efficacy of the three-drug combination of antimicrotubule agents.

Adenocarcinoma↗
PubMed2003

Weekly paclitaxel, estramustine phosphate, and oral etoposide in the treatment of hormone-refractory prostate carcinoma: results of a Minnie Pearl Cancer Research Network phase II trial.

BACKGROUND: The objective of the current study was to evaluate the efficacy and toxicity of weekly paclitaxel, oral etoposide, and estramustine phosphate in the treatment of patients with advanced, hormone-refractory prostate carcinoma. METHODS: Patients with hormone-refractory prostate carcinoma who had received no more than one previous chemotherapy regimen were eligible for this trial. Forty-two patients were treated between February 1998 and March 2000. Toxicity was excessive in the first 3 patients treated (Grade 3-4 leukopenia, 3 patients; death due to sepsis, 1 patient); the remaining 39 patients received lower doses of etoposide and estramustine phosphate (paclitaxel 50 mg/m(2) as a 1-hour, intravenous infusion on Days 1, 8, 15; etoposide 50 mg orally twice daily on Days 1-10; and estramustine phosphate 280 mg orally 3 times daily on Days 1-10). Courses were repeated every 28 days. Patients were evaluated for objective and/or serologic response after two courses of treatment; responding patients continued treatment for six courses. RESULTS: Fourteen of 40 evaluable patients (35%) had either an objective response or a serologic response to treatment. The median survival for the entire group was 9.5 months, with 1-year, 2-year, and 3-year survival rates of 38%, 12%, and 10%, respectively. Neutropenia was the most common Grade 3-4 toxicity and occurred in 38% of patients (11% of courses). Thirteen patients (33%) had severe fatigue, and 2 patients had treatment-related deaths due to sepsis. CONCLUSIONS: Although the three-drug combination had activity in patients with hormone-refractory prostate carcinoma, the results did not appear any better than the results achieved with less toxic taxane/estramustine phosphate combinations. Further development of this three-drug regimen is not recommended.

Adenocarcinoma↗
PubMed2003

A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma: Cancer and Leukemia Group B 99813.

BACKGROUND: The authors determined the safety and efficacy of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor (G-CSF) support in patients with hormone-refractory prostate carcinoma. METHODS: In the current multicenter, cooperative group study, patients with advanced prostate carcinoma whose disease progressed despite androgen deprivation therapy were treated with a combination of oral estramustine(240 mg three times per day for 5 days), 70 mg/m2 of docetaxel, and carboplatin at a dose of (area under the curve) 5. G-CSF was used to minimize the neutropenia associated with this regimen. Each cycle was repeated every 21 days. RESULTS: Forty patients were treated with a median of 7 cycles of therapy. Of the 34 evaluable patients with elevated pretreatment prostate-specific antigen (PSA) levels, 23 (68%) had a > or = 50% decline in PSA and 20 (59%) had a > or = 75% decline. Twenty-one patients had measurable disease, with 1 complete response (5%) and 10 partial responses (47%), for an overall measurable response rate of 52% (95% confidence interval [95% CI], 30-74%). The most common Grade 3 or Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria) included neutropenia in 23% of patients, thrombocytopenia in 13%, and fatigue in 13%. Febrile neutropenia occurred in 1 patient (3%). The overall median time to disease progression was 8.1 months (95% CI, 6-10 months) and the overall survival period was 19 months (95% CI, 13-26 months). CONCLUSIONS: The combination of estramustine, docetaxel, and carboplatin with G-CSF support was found to have significant clinical activity with an acceptable toxicity profile in patients with progressive hormone-refractory prostate carcinoma.

Aged↗
PubMed1989

Polymorphism of estramustine.

As the solubility in water of the cytotoxic drug estramustine is less than 1 mg/L, polymorphism can have an impact on the bioavailability of orally administered drug. Therefore, the solid state characteristics of estramustine samples, crystallized from different solvents, were investigated by means of X-ray crystallography, thermal analysis, and IR spectroscopy. The DSC data indicated the existence of several phases. Four forms--A, B, C, and D--were confirmed. Phase A was obtained when crystallizing from solvents with a moderate or low dieletric constant (less than approximately 24). This form was an anhydrate and found to be the stable one. When crystallizing from methanol, metastable solvates, with approximately 0.5 mol for phase B or approximately 1 mol for form C, were precipitated. Both types were transformed to phase A during storage. This desolvation was accelerated by heating. Crystallizing from a mixture of acetone and water resulted in a monohydrate, form D, which was converted to the anhydrous type A upon heating. As forms B, C, and D were solvates which transformed to another crystal form upon desolvation, they were polymorphic solvates of the anhydrate, type A. Symmetry and unit cell dimensions of the stable form of estramustine (phase A) were determined by means of a single-crystal X-ray technique (orthorhombic, a = 23.90, b = 20.69, c = 8.76, space group P212121). In addition, the crystallographic parameters of form D were deduced from calculations based on powder diffraction data.

Chemical Phenomena↗