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1

Stearns, M. E., and K. D. Tew. "Estramustine binds MAP-2 to inhibit microtubule assembly in vitro." Journal of Cell Science 89, no. 3 (1988): 331–42. http://dx.doi.org/10.1242/jcs.89.3.331.

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We have investigated the ability of estramustine to bind to rat brain microtubule-associated proteins (MAPs) and purified MAP-2 in vitro. [3H]estramustine's relative affinity for tubulin and MAPs was assessed by gel filtration chromatography, immunoprecipitation and binding assays. Scatchard analysis demonstrated a specific affinity of the drug for MAP-2. Calculations from kinetic parameters and non-linear regression analysis gave a Kd of 15 microM, and a Bmax of 3.4 × 10(−7)M ml-1. Extrapolation of this value suggested that each MAP-2 molecule binds approximately 20 molecules of estramustine.
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2

&NA;. "Estramustine." Reactions Weekly &NA;, no. 913 (2002): 7. http://dx.doi.org/10.2165/00128415-200209130-00019.

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3

&NA;. "Estramustine." Reactions Weekly &NA;, no. 773 (1999): 9. http://dx.doi.org/10.2165/00128415-199907730-00022.

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4

&NA;. "Estramustine phosphate." Drugs & Therapy Perspectives 6, no. 11 (1995): 5–8. http://dx.doi.org/10.2165/00042310-199506110-00002.

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5

Sangrajrang, Suleeporn, Fabien Calvo, and Arlette Fellous. "Estramustine resistance." General Pharmacology: The Vascular System 33, no. 2 (1999): 107–13. http://dx.doi.org/10.1016/s0306-3623(98)00272-9.

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6

Fizazi, K., G. R. Hudes, W. R. Berry, et al. "A meta-analysis of individual patient data from randomized trials assessing chemotherapy with and without estramustine in patients with castration-refractory prostate cancer." Journal of Clinical Oncology 24, no. 18_suppl (2006): 4561. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.4561.

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4561 Background: Estramustine phosphate is a mustard-estradiol conjugate, with evidence of both hormonal and non-hormonal effects. In phase II trials, the response rates of microtubule inhibitors are increased when combined with estramustine. Morbidity includes notably thrombosis in about 7% of cases. Whether combining estramustine with chemotherapy increases survival in castration-refractory prostate cancer (CRPC) is still controversial. Methods: Data from all published and unpublished prospective randomized trials assessing chemotherapy + estramustine versus chemotherapy alone in CRPC were s
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7

Stearns, M. E., M. Wang, and O. Sousa. "Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion." Journal of Cell Science 98, no. 1 (1991): 55–63. http://dx.doi.org/10.1242/jcs.98.1.55.

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Estramustine is a novel anti-microtubule drug shown to bind MAP-1 and MAP-2 (microtubule-associated proteins) in vitro. In this paper we have shown that estramustine specifically binds MAP-1A in Du 145a cells, resulting in disruption of MAP-1A microtubules and inhibition of type IV collagenase secretion. Immunofluorescence studies revealed that at 30 microM levels estramustine blocked type IV collagenase secretion by partial disruption of the MAP-1A microtubule networks. Immunoprecipitation studies with polyclonal antibodies provided quantitative evidence that 30–60 microM estramustine blocked
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8

Stearns, M. E., M. Wang, K. D. Tew, and L. I. Binder. "Estramustine binds a MAP-1-like protein to inhibit microtubule assembly in vitro and disrupt microtubule organization in DU 145 cells." Journal of Cell Biology 107, no. 6 (1988): 2647–56. http://dx.doi.org/10.1083/jcb.107.6.2647.

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The twofold purpose of the study was (a) to determine if a MAP-1-like protein was expressed in human prostatic DU 145 cells and (b) to demonstrate whether a novel antimicrotubule drug, estramustine, binds the MAP-1-like protein to disrupt microtubules. SDS-PAGE and Western blots showed that a 330-kD protein was associated with microtubules isolated in an assembly buffer containing 10 microM taxol and 10 mM adenylylimidodiphosphate. After purification to homogeneity on an A5m agarose column, the 330-kD protein was found to promote 6 S tubulin assembly. Turbidimetric (A350), SDS-PAGE, and electr
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9

&NA;. "Estramustine phosphate sodium." Reactions Weekly &NA;, no. 1312 (2010): 24. http://dx.doi.org/10.2165/00128415-201013120-00084.

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10

Simpson, Dene, and Antona J. Wagstaff. "Estramustine Phosphate Sodium." American Journal of Cancer 2, no. 5 (2003): 373–90. http://dx.doi.org/10.2165/00024669-200302050-00013.

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11

Perry, Caroline M., and Donna McTavish. "Estramustine Phosphate Sodium." Drugs & Aging 7, no. 1 (1995): 49–74. http://dx.doi.org/10.2165/00002512-199507010-00006.

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12

&NA;. "Estramustine phosphate sodium." Reactions Weekly &NA;, no. 920 (2002): 7. http://dx.doi.org/10.2165/00128415-200209200-00017.

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13

&NA;. "Dexamethasone/docetaxel/estramustine." Reactions Weekly &NA;, no. 1337 (2011): 16–17. http://dx.doi.org/10.2165/00128415-201113370-00046.

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14

Wadsten, Tommy, and Nils-Olof Lindberg. "Polymorphism of Estramustine." Journal of Pharmaceutical Sciences 78, no. 7 (1989): 563–66. http://dx.doi.org/10.1002/jps.2600780711.

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15

Giribone, Danilo, and Erminia Fontana. "Synthesis of estromustine, estramustine and estramustine phosphate labelled with deuterium." Journal of Labelled Compounds and Radiopharmaceuticals 47, no. 2 (2004): 161–65. http://dx.doi.org/10.1002/jlcr.809.

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16

&NA;. "Cilazapril/estramustine phosphate sodium." Reactions Weekly &NA;, no. 1159 (2007): 12. http://dx.doi.org/10.2165/00128415-200711590-00034.

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17

Bjermer, Leif, Eva Von Schoultz, Bo Norberg, and Roger Henriksson. "Estramustine inhibits monocyte phagocytosis." Prostate 13, no. 1 (1988): 49–55. http://dx.doi.org/10.1002/pros.2990130106.

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18

von Schoultz, Eva, Tommy Bergenheim, Kjell Grankvist, and Roger Henriksson. "Estramustine binding protein in human brain-tumor tissue." Journal of Neurosurgery 74, no. 6 (1991): 962–64. http://dx.doi.org/10.3171/jns.1991.74.6.0962.

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✓ Estramustine, an estradiol-17β and nornitrogen mustard complex, is used in the treatment of advanced prostatic carcinoma. A specific estramustine binding protein (EMBP) is important for its cytotoxic action, and the presence of EMBP has previously been demonstrated in rat and human prostatic cancer tissue. Significant levels of EMBP were detected by radioimmunoassay in human brain-tumor tissue. The EMBP concentrations (expressed as ng/mg protein) in 16 astrocytomas (mean 2.6 ng/mg, range 0.5 to 6.2 ng/mg) and seven meningiomas (mean 5.1 ng/mg, range 0.3 to 9.3 ng/mg) were significantly highe
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19

Bissinger, Rosi, Paola Modicano, Leonie Frauenfeld, et al. "Estramustine-Induced Suicidal Erythrocyte Death." Cellular Physiology and Biochemistry 32, no. 5 (2013): 1426–36. http://dx.doi.org/10.1159/000356580.

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20

Karlsson, A. E., A. Tommy Bergenheim, Per Björk, and Roger Henriksson. "Estramustine-binding protein in meningioma." Acta Neuropathologica 98, no. 2 (1999): 135–40. http://dx.doi.org/10.1007/s004010051061.

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21

Lidström, Pelle, Thomas A. Bonasera, Marcela Marquez-M, Sten Nilsson, Mats Bergström, and Bengt Långström. "Synthesis and In Vitro Evaluation of [carbonyl-11C]Estramustine and [carbonyl-11C]Estramustine Phosphate." Steroids 63, no. 4 (1998): 228–34. http://dx.doi.org/10.1016/s0039-128x(98)00013-0.

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22

von Schoultz, E., D. Lundblad, J. Bergh, K. Grankvist, and R. Henriksson. "Estramustine binding protein and anti-proliferative effect of estramustine in human glioma cell lines." British Journal of Cancer 58, no. 3 (1988): 326–29. http://dx.doi.org/10.1038/bjc.1988.212.

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23

Machiels, Jean-Pascal, Filomena Mazzeo, Marylene Clausse, et al. "Prospective Randomized Study Comparing Docetaxel, Estramustine, and Prednisone With Docetaxel and Prednisone in Metastatic Hormone-Refractory Prostate Cancer." Journal of Clinical Oncology 26, no. 32 (2008): 5261–68. http://dx.doi.org/10.1200/jco.2008.16.9524.

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PurposeTo assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer.Patients and MethodsOne hundred fifty patients were randomly assigned to D alone (35 mg/m2on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA ≥ 50% from baseline. The study was powered
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24

Edgren, Maliha, Jan-Erik Westlin, Henry Letocha, Hans Nordgren, Karl-Mikael Kälkner, and Sten Nilsson. "Estramustine-Binding Protein (EMBP) in Renal Cell Carcinoma Immunohistochemistry, Immunoscintigraphy and in Vitro Estramustine Effects." Acta Oncologica 35, no. 4 (1996): 483–88. http://dx.doi.org/10.3109/02841869609109927.

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25

Stålberg, Kaarlo, Kalevi Kairemo, Sirkka-Liisa Karonen, Antti Jekunen, Kimmo Taari, and Sakari Rannikko. "Radioiodinated estramustine phosphate and estramustine binding protein Antibody accumulate in the prostate of a mouse." Prostate 32, no. 1 (1997): 1–8. http://dx.doi.org/10.1002/(sici)1097-0045(19970615)32:1<1::aid-pros1>3.0.co;2-q.

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26

Stearns, M. E., D. P. Jenkins, and K. D. Tew. "Dansylated estramustine, a fluorescent probe for studies of estramustine uptake and identification of intracellular targets." Proceedings of the National Academy of Sciences 82, no. 24 (1985): 8483–87. http://dx.doi.org/10.1073/pnas.82.24.8483.

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27

&NA;. "Docetaxel + estramustine + prednisone has "significant impact"." Inpharma Weekly &NA;, no. 1484 (2005): 17. http://dx.doi.org/10.2165/00128413-200514840-00047.

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28

Bergenheim, A. Tommy, and Roger Henriksson. "Pharmacokinetics and Pharmacodynamics of Estramustine Phosphate." Clinical Pharmacokinetics 34, no. 2 (1998): 163–72. http://dx.doi.org/10.2165/00003088-199834020-00004.

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29

&NA;. "Estramustine plus vinorelbine for prostate cancer?" Inpharma Weekly &NA;, no. 1142 (1998): 19. http://dx.doi.org/10.2165/00128413-199811420-00038.

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30

Laing, Naomi, Bjorn Dahllöf, Beryl Hartley-Asp, Sulabha Ranganathan, and Kenneth D. Tew. "Interaction of Estramustine with Tubulin Isotypes†." Biochemistry 36, no. 4 (1997): 871–78. http://dx.doi.org/10.1021/bi961445w.

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31

Solimando, Dominic A., J. Aubrey Waddell, and Andrew J. Watts. "Docetaxel and Estramustine for Prostate Cancer." Hospital Pharmacy 44, no. 6 (2009): 473–78. http://dx.doi.org/10.1310/hpj4406-473.

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32

Bradbury, Jane. "Docetaxel with estramustine for prostate cancer." Lancet Oncology 8, no. 6 (2007): 470. http://dx.doi.org/10.1016/s1470-2045(07)70165-1.

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33

Pedrotti, Barbara, and Khalid Islam. "Estramustine phosphate but not estramustine inhibits the interaction of microtubule associated protein 2 (MAP2) with actin filaments." FEBS Letters 403, no. 2 (1997): 123–26. http://dx.doi.org/10.1016/s0014-5793(96)01524-4.

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34

&NA;. "Ixabepilone ?? estramustine active in metastatic prostate cancer." Inpharma Weekly &NA;, no. 1486 (2005): 8. http://dx.doi.org/10.2165/00128413-200514860-00020.

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35

Olson, Eric L., and Young E. Whang. "Hypertriglyceridemia and Pancreatitis Associated With Estramustine Phosphate." American Journal of Clinical Oncology 25, no. 4 (2002): 342–43. http://dx.doi.org/10.1097/00000421-200208000-00004.

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36

Walz, P., P. Björk, K. Edman, P. Gunnarsson, and B. Hartley-Asp. "Uptake and Distribution of the Estramustine-Phosphate Metabolite Estramustine after Single-Dose Injection in Patients with Prostatic Cancer." Aktuelle Urologie 27, S 1 (1996): 92–93. http://dx.doi.org/10.1055/s-2008-1055666.

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37

Bergenheim, AT, PO Gunnarsson, K. Edman, E. von Schoultz, MI Hariz, and R. Henriksson. "Uptake and retention of estramustine and the presence of estramustine binding protein in malignant brain tumours in humans." British Journal of Cancer 67, no. 2 (1993): 358–61. http://dx.doi.org/10.1038/bjc.1993.65.

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38

Bosset, Pierre-Olivier, Laurence Albiges, Agnes Laplanche, et al. "Long-term tolerance of neoadjuvant docetaxel/estramustine chemotherapy in patients with high-risk localized prostate cancer treated at IGR in the GETUG 12 phase III trial." Journal of Clinical Oncology 31, no. 6_suppl (2013): 168. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.168.

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168 Background: The GETUG 12 phase III trial tested the adjunction of docetaxel-estramustine to standard treatment in 413 patients with high-risk prostate cancer (Eur J Cancer 2012, 48: 209-17). Patients in both arms received androgen deprivation therapy (ADT) for 3 years plus local treatment (radiotherapy: 87%, median dose: 74 Gy). Pts in the chemotherapy arm also received 4 cycles of docetaxel 70mg/m2 /3weeks + estramustine 10 mg/kg/d d1-5, repeated every 3 weeks. Immediate tolerance was acceptable with only 2% of febrile neutropenia and no toxic deaths. As the long-term impact of chemothera
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39

Oudard, Stéphane, Eugeniu Banu, Philippe Beuzeboc, et al. "Multicenter Randomized Phase II Study of Two Schedules of Docetaxel, Estramustine, and Prednisone Versus Mitoxantrone Plus Prednisone in Patients With Metastatic Hormone-Refractory Prostate Cancer." Journal of Clinical Oncology 23, no. 15 (2005): 3343–51. http://dx.doi.org/10.1200/jco.2005.12.187.

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Purpose Mitoxantrone-corticosteroid is currently the standard palliative treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical trials documented the high activity of the docetaxel-estramustine combination. We conducted a randomized phase II study to evaluate prostate-specific antigen (PSA) response (primary end point) and safety of two docetaxel-estramustine-prednisone (DEP) regimens and mitoxantrone-prednisone (MP). Patients and Methods One hundred thirty metastatic HRPC patients were randomly assigned to receive docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 an
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40

Hudes, Gary, Lawrence Einhorn, Eric Ross, et al. "Vinblastine Versus Vinblastine Plus Oral Estramustine Phosphate for Patients With Hormone-Refractory Prostate Cancer: A Hoosier Oncology Group and Fox Chase Network Phase III Trial." Journal of Clinical Oncology 17, no. 10 (1999): 3160–66. http://dx.doi.org/10.1200/jco.1999.17.10.3160.

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PURPOSE: To compare vinblastine versus the combination of vinblastine plus estramustine as treatment for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A total of 201 patients with metastatic prostate cancer, progressive after hormonal therapy and antiandrogen withdrawal (if prior antiandrogen treatment), were randomized to receive vinblastine (V) 4 mg/m2 by intravenous bolus weekly for 6 weeks followed by 2 weeks off, either alone or together with estramustine phosphate (EM-V) 600 mg/m2 PO days 1 through 42, repeated every 8 weeks. Of 193 eligible patients, 98
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41

Pienta, K. J., B. Redman, M. Hussain, et al. "Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate." Journal of Clinical Oncology 12, no. 10 (1994): 2005–12. http://dx.doi.org/10.1200/jco.1994.12.10.2005.

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PURPOSE Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression. RESULTS Forty-two patients have been enrolled onto
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42

Fulfaro, F., V. Serretta, G. Cicero, et al. "A randomized phase II study of estramustine phosphate versus estramustine phosphate plus etoposide in hormone refractory prostate cancer (HRPC)." Journal of Clinical Oncology 26, no. 15_suppl (2008): 20632. http://dx.doi.org/10.1200/jco.2008.26.15_suppl.20632.

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43

Petrylak, Daniel P., Robert B. Macarthur, John O'Connor, et al. "Phase I Trial of Docetaxel With Estramustine in Androgen-Independent Prostate Cancer." Journal of Clinical Oncology 17, no. 3 (1999): 958. http://dx.doi.org/10.1200/jco.1999.17.3.958.

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PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were ass
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44

Smith, David C., Peg Esper, Myla Strawderman, Bruce Redman, and Kenneth J. Pienta. "Phase II Trial of Oral Estramustine, Oral Etoposide, and Intravenous Paclitaxel in Hormone-Refractory Prostate Cancer." Journal of Clinical Oncology 17, no. 6 (1999): 1664. http://dx.doi.org/10.1200/jco.1999.17.6.1664.

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PURPOSE: To evaluate the combination of intravenous (IV) paclitaxel, oral estramustine, and oral etoposide in patients with advanced hormone-refractory prostate cancer. PATIENTS AND METHODS: Forty patients with carcinoma of the prostate that was progressing despite hormonal therapy and who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled onto this phase II trial. Patients were treated with oral estramustine 280 mg tid and oral etoposide 100 mg/d for 7 days, with paclitaxel 135 mg/m2 IV over 1 hour on day 2 of each 21-day treatment cycle. Patients
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45

&NA;. "Estramustine phosphate sodium-based regimen in prostate cancer." Inpharma Weekly &NA;, no. 1337 (2002): 12. http://dx.doi.org/10.2165/00128413-200213370-00028.

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46

&NA;. "Docetaxel/estramustine increases survival in advanced prostate cancer." Inpharma Weekly &NA;, no. 1459 (2004): 13. http://dx.doi.org/10.2165/00128413-200414590-00034.

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47

Benson, Ralph, and Beryl Hartley-Asp. "Mechanisms of Action and Clinical Uses of Estramustine." Cancer Investigation 8, no. 3-4 (1990): 375–80. http://dx.doi.org/10.3109/07357909009012056.

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48

Jennings, A. M., L. Z. Solomon, P. Sharpe, M. C. Hayes, A. J. Cooper, and B. R. Birch. "Estramustine Reversal of Resistance to Intravesical Epirubicin Chemotherapy." European Urology 35, no. 4 (1999): 327–35. http://dx.doi.org/10.1159/000019871.

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49

Mcgregory, Michael, Dominic A. Solimando, and J. Aubrey Waddell. "Taxanes and Estramustine for Hormone-Refractory Prostate Cancer." Hospital Pharmacy 37, no. 8 (2002): 816–86. http://dx.doi.org/10.1177/001857870203700803.

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The increasing complexity of cancer chemotherapy makes it mandatory that pharmacists be familiar with these highly toxic agents. This column focuses on the commercially available and investigational agents used to treat malignant diseases, reviewing issues related to the preparation, dispensing, and administration of cancer chemotherapy.
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50

Rosenthal, M. A., D. Raghavan, R. Stuart-Harris, S. Ackland, and J. Grygiel. "THE TREATMENT OF DISSEMINATED PROSTATE CANCER WITH ESTRAMUSTINE." ANZ Journal of Surgery 62, no. 11 (1992): 871–73. http://dx.doi.org/10.1111/j.1445-2197.1992.tb06942.x.

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