DOCSLIB.ORG

527.Full.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
527.Full.Pdf Vol. 4, 52 7-534, Marc/i 1998 Clinical Cancer Research 527 Review Update on Endocrine Therapy for Breast Cancer Aman U. Buzdar’ and Gabriel Hortobagyi research is ongoing to find new agents with greater efficacy and The University of Texas M. D. Anderson Cancer Center, Houston, improved safety profiles. Certain hormones (estrogens) can have Texas 77030 a major positive impact on the general health of women (i.e., preventing osteoporosis, lowering serum lipid levels, and reduc- ing menopausal symptoms). Thus, new endocrine agents that Abstract improve general health in addition to having antitumor activity The choice of endocrine agent for breast cancer de- would be highly desirable both in the breast cancer setting and pends on the menopausal status of the patient, the stage of for hormone replacement in healthy postmenopausal women disease, prognostic factors, and the toxicity profile of the (2, 3). agent. Endocrine therapies are typically given sequentially, The decision to use endocrine therapy for breast cancer is with the least toxic therapy given first. Tamoxifen is consid- based on a number of prognostic factors. Probably the most ered first-line endocrine therapy for all stages of breast important indicator of response to endocrine therapy is the cancer. New antiestrogens in development include nonste- presence of ERs and PRs in the tumor. Approximately 30% of roidal agents related to tamoxifen and pure steroidal anties- unselected breast cancer patients respond to endocrine therapy. trogens Luteinizing hormone-releasing hormone agonists Estrogen receptor and progesterone receptor data help to iden- are an effective form of endocrine therapy for premeno- tify patient subgroups who may benefit from endocrine therapy. pausal women with advanced breast cancer, and aromatase Endocrine therapy response rates in advanced disease average inhibitors are effective in postmenopausal women. Newer 33% in tumors positive for one hormone receptor and 50-70% and more selective aromatase inhibitors that are p.o. active in tumors positive for both hormone receptors (4). Furthermore, and have improved side-effect profiles have been developed. 20-30% of patients treated with endocrine therapy have stable Recent trials have found these agents to improve survival in disease and achieve similar benefits as those patients responding comparison to the progestins; thus, aromatase inhibitors are to endocrine therapy. Hormone receptor positivity is more com- replacing progestins as second-line therapy for metastatic mon in postmenopausal than premenopausal breast cancer pa- disease. Current trials are examining the potential role of tients (Fig. 1 ; Ref. 5). Other predictors of response include prior aromatase inhibitors as first-line therapy for metastatic dis- response to endocrine therapy, soft tissue or bony (as opposed to ease or as adjuvant therapy for early disease. The antipro- visceral) metastases, long disease-free interval, older age, well- gestins and antiandrogens studied thus far have had only differentiated tumors, and HER-2/neu negativity. limited success in breast cancer clinical trials. Most endocrine agents act by either blocking the produc- tion of estrogen (ovarian ablation and aromatase inhibitors) or Introduction the action of estrogen at the cellular level (antiestrogens); how- It has been over a century since Beatson demonstrated that ever, for some agents (e.g. , supraphysiological doses of estro- oophorectomy was effective for treating advanced breast cancer. gens, androgens, and progestins), the mechanism of action is ( 1) Since then, endocrine therapies have become firmly estab- unknown. The choice of endocrine agent depends on the men- lished for managing all stages of breast cancer. opausal status of the patient, because this factor determines the In the last few years, many advances have been made in source of estrogen: ovarian or adrenal (peripheral; Fig. 2). endocrine approaches to breast cancer therapy. Treatment In premenopausal women, the ovary actively produces high choices have been refined and optimized by the development of basal estrogen levels. One treatment option is ovarian ablation, assays for the presence of estrogen and progesterone receptors which can be accomplished by surgery, radiation, or LHRH in tumors. Surgical techniques (i.e., oophorectomy, hypophy- agonist therapy. Of the surgical techniques, oophorectomy is sectomy, and adrenalectomy) have been largely replaced by a still used in premenopausal women with advanced breast cancer, variety of pharmaceuticals (i.e., antiestrogens, LHRH2 agonists, but hypophysectomy and adrenalectomy were abandoned once aromatase inhibitors, androgens. estrogens, and progestins), and pharmacological approaches became available (6). Antiestrogen therapy (i.e., tamoxifen) has proven effective in premenopausal patients as well. In postmenopausal women, ovarian function has ceased, Received 9/22/97: revised 12/16/97: accepted 12/16/97. and estrogen is primarily produced in peripheral tissues such as The costs of publication of this article were defrayed in part by the fat and muscle. Endocrine therapies for postmenopausal women payment of page charges. This article must therefore be hereby marked include antiestrogens, progestins, and aromatase inhibitors. advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Although endocrine therapies operate through different ‘To whom requests for reprints should be addressed, at Department of mechanisms, they often have similar objective response rates. Breast Medical Oncology, M. D. Anderson Cancer Center, Box 56, Because breast cancer is a progressive disease and the develop- 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792- ment of drug resistance is common, endocrine therapies are 2817; Fax: (713) 794-4385. given sequentially, with the least toxic therapy given first. 2 The abbreviations used are: LHRH, luteininzing hormonereleasing hormone: ER, estrogen receptor; PR, progesterone receptor; FDA, Food In some cases, endocrine therapies have been almost en- and Drug Administration: AG. aminoglutethimide. tirely abandoned on the basis of toxicity. For example, diethyl- Downloaded from clincancerres.aacrjournals.org on September 28, 2021. © 1998 American Association for Cancer Research. 528 Endocrine Therapy for Breast Cancer 70 60 50 Hypothalamus 0 o Premenopausal 0 #{149}Postmenopausal 0 40 47 ‘4- 0 Premenopausal Postmenopausal 30 0 U 0 20 a- (FSH7/’ 10 Gonadotrophins Adrenal gland 0 irJ1 Ovary ER+, PR+ ER+, PR- ER-, PR+ ER-, PR- Prolactin Receptor Status Growth hormone Fig. 1 Breast cancer patients grouped according to their menopausal Corticosterolds status and the hormone receptor status of their tumors. Progesterone ProgesteroneI Androgens stilbestrol was introduced in the 1940s as an endocrine therapy for postmenopausal advanced breast cancer (6). Because dieth- 1 ylstilbestrol was associated with side effects such as upper Peripheral 1ssues gastrointestinal distress, thromboembolic risk, fluid retention, (e.g. muscle, fat, breast tumors) stress incontinence, and withdrawal bleeding, it all but disap- peared from the clinic after the introduction of tamoxifen in the 1970s. Likewise, androgens are associated with virilization, 1 nausea, hepatotoxicity with cholestasis, increased libido, and Estrogens hypercalcemia; as a consequence. they have been relegated to Fig. 2 Routes of synthesis of estrogen and progesterone in premeno- fourth-line therapy for advanced breast cancer in postmeno- pausal and postmenopausal women. pausal women. Current and Future Directions in Endocrine Therapy node-negative breast cancer (10). However, the Eastern Coop- Nonsteroidal Antiestrogens erative Oncology Group recently published preliminary results Tamoxifen Tamoxifen (Fig. 3) is the first-line endocrine (1 1) of a trial showing prolonged disease-free survival with therapy for all stages of breast cancer. It was first approved by longer than 5 years compared with 5 years in women with the FDA in 1977 for the treatment of advanced breast cancer in ER-positive breast cancer. postmenopausal women and has since been approved for: (a) the Because tamoxifen was found to prevent new tumors from treatment of advanced breast cancer in premenopausal women; developing in the opposite breast, the drug is presently being (b) use with chemotherapy; (c) adjuvant monotherapy in post- studied in worldwide breast cancer prevention trials in healthy menopausal women with node-positive breast cancer; (d) the women at increased risk for the disease ( 12). The use of tamox- treatment of node-negative breast cancer; and (e) male breast ifen in healthy women has been controversial. Although tamox- cancer. ifen is generally considered safer than alternative endocrine In postmenopausal women with advanced breast cancer, therapies such as androgens, estrogens, and progestins, it is not tamoxifen induces objective responses in about one-third of without toxicity. In addition to vasomotor and gynecological unselected patients; a higher response rate is observed in women side-effects (e.g., hot flashes, vaginal discharge, and irregular with ER-positive tumors (7). Adjuvant therapy with tamoxifen menses) and an increase in the rate of thromboembolic events has reduced recurrence rates, mortality, and the incidence of (1% in the B-14 trial; Ref. 10), the drug has been associated with contralateral breast cancer (8). The duration for which to give a modest increase in the risk for endometrial cancer (2 cases per adjuvant
Load more

Recommended publications
  • OECD Environment Health and Safety Publications Series on Testing and Assessment No
    OECD Environment Health and Safety Publications Series on Testing and Assessment No. 21 Detailed Review Paper Appraisal of Test Methods for Sex Hormone Disrupting Chemicals Environment Directorate ORGANISATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT Paris May 2001 1 Also Published in the Series Testing and Assessment: No. 1, Guidance Document for the Development of OECD Guidelines for Testing of Chemicals (1993; reformatted 1995) No. 2, Detailed Review Paper on Biodegradability Testing (1995) No. 3, Guidance Document for Aquatic Effects Assessment (1995) No. 4, Report of the OECD Workshop on Environmental Hazard/Risk Assessment (1995) No. 5, Report of the SETAC/OECD Workshop on Avian Toxicity Testing (1996) No. 6, Report of the Final Ring-test of the Daphnia magna Reproduction Test (1997) No. 7, Guidance Document on Direct Phototransformation of Chemicals in Water (1997) No. 8, Report of the OECD Workshop on Sharing Information about New Industrial Chemicals Assessment (1997) No. 9 Guidance Document for the Conduct of Studies of Occupational Exposure to Pesticides During Agricultural Application (1997) No. 10, Report of the OECD Workshop on Statistical Analysis of Aquatic Toxicity Data (1998) No. 11, Detailed Review Paper on Aquatic Testing Methods for Pesticides and industrial Chemicals (1998) No. 12, Detailed Review Document on Classification Systems for Germ Cell Mutagenicity in OECD Member Countries (1998) No. 13, Detailed Review Document on Classification Systems for Sensitising Substances in OECD Member Countries 1998) No. 14, Detailed Review Document on Classification Systems for Eye Irritation/Corrosion in OECD Member Countries (1998) No. 15, Detailed Review Document on Classification Systems for Reproductive Toxicity in OECD Member Countries (1998) No.
    [Show full text]
  • 2019 AAPLOG Position Statement on Abortion Pill Reversal
    2019 AAPLOG Position Statement on Abortion Pill Reversal Some women change their mind about abortion after taking the first drug of the abortion regimen. For those women, Abortion Pill Rescue offers a medically sound choice to attempt to reverse the effects of Mifepristone, and to save their baby. The American Association of Pro-Life Obstetricians and Gynecologists strongly supports efforts to require all women presenting for abortion to be given information about abortion pill reversal as part of informed consent prior to abortion. Biological Background on the Chemical Abortion Regimen and Abortion Pill Reversal The chemical abortion regimen consists of two drugs: Mifeprex (a.k.a. mifepristone or RU-486) and Cytotec (misoprostol). Mifeprex is the first drug developed in a class of drugs called “selective progesterone receptor blockers”. This class also includes Ella (ulipristal) and onapristone among others. Mifeprex is the first drug approved by the FDA for inducing abortion. However, Mifeprex by itself is only effective at accomplishing embryo demise about 75% of the time1. So, roughly one out of four women who take Mifeprex alone will have an unborn child in utero who continues to live. So, in order to increase the number of women who complete the abortion, a second drug, Cytotec (misoprostol), is administered to the woman. Cytotec is of the class of drugs known as prostaglandins. Other prostaglandins can also be used for this purpose (e.g. gemeprost) Prostaglandins cause the uterus to contract, forcing the expulsion of the unborn
    [Show full text]
  • The Clinical Efficacy of Progesterone Antagonists in Breast Cancer ------ .__..__
    8 The clinical efficacy of progesterone antagonists in breast cancer --------_.__..__. Walter Jonat, Marius Giurescu, John FR Robertson CONTENTS • Introduction • Onapristone • Mlfepristone • Summary INTRODUCTION indication of a functional PgR.4 As described in Chapter 14, substantial in vitro and in vivo The search for active and safe alternatives to evidence suggests that PgR serves as a biologi­ current systemic therapies is one of the main cally important molecule in breast cancer objectives of current breast cancer research. behaviour. Moreover, preclinical studies indi­ Over the last three decades since the discovery cate that blockade of PgR function inhibits pro­ of the estrogen receptor (ER), the development liferation and induces apoptosis (see Chapter of new endocrine agents has in the main been 14). Therefore, clinically practical PgR inhibitors aimed at either preventing the production of have been developed. These are overtly active estrogens (e.g. ovarian ablation with small molecuk'S that appear to function by gonadotropin-releasing hormone (GnRH) ana­ binding to PgR and inhibiting pathways down­ logues, aromatase inhibition) or blocking their stream of PgR. Two agents, onapristone and effect by competition for ER (e.g. selective ER mifepristone, have been evaluated in clinical modulators (SERMs) and pure antiestrogens). trials, and, as described below, have activity in Such developments have focused, indirectly or patients with metastatic disease. Although com­ directly, on the ER as a target for manipulation mercial support for these two agents has of tumour growth. This approach is supported recently waned, the concept of PgR inhibition by the finding that the response to such thera­ in breast cancer is sufficiently well founded to pies is related to the expression of ER by breast justify its inclusion in any textbook of endocrine tumours.13 However, it is also known that therapy.
    [Show full text]
  • The Pure Progesterone Receptor (PR) Antagonist Onapristone Enhances
    The pure progesterone receptor (PR) antagonist onapristone enhances the anti-proliferative effects of CDK4/6 inhibitors and fulvestrant, a SERD, in preclinical in-vitro breast cancer models Deepak Lala1, PhD; Tasir Haque1, PhD; Hannah Feinman2; Jianghong Wu2, PhD; Yuren Wang2, PhD; Amy Dwyer3, PhD; Thu Truong3, PhD and Carol Lange3, PhD, Institutions: 1Context Therapeutics, Philadelphia, PA, United States, 19104; 2Reaction Biology Corporation, Malvern, PA, United States, 19355 and 3University of Minnesota Masonic Cancer Center, Minneapolis, MN, United States, 55455. San Antonio Breast Cancer Symposium® - December 4-8, 2018 ABSTRACT METHODS A Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer related T47D cells were treated with various concentrations of onapristone or palbociclib in media death in women. Around 5–10% of cases are metastatic at diagnosis, and close to 30% of patients with containing 10%FBS.10 days after treatment cell viability was determined using Cell Titer Glo. early stage disease will relapse with metastatic disease. Anti-estrogen therapy is an important treatment 1x agarose, IMEM, 10% DCC, 1% P/S 1x agarose, 2.4x103 cells, Fulv or Palbo Cells were also treated with increasing concentrations of palbociclib in the absence or presence Solidify 5 min at 4°C Solidify 5 min at 4°C modality for hormone receptor-positive (HR+) metastatic breast cancer (mBCa) as mono- or combination of onapristone and analyzed for cell proliferation after 10 days and for gene expression after 16 (e.g. with CDK4/6 inhibitors) first-line (1L) therapy. Unfortunately, despite the high rate of clinical benefit hours of treatment.
    [Show full text]
  • Onapristone Extended Release: Safety Evaluation from Phase I–II Studies with an Emphasis on Hepatotoxicity
    Drug Safety https://doi.org/10.1007/s40264-020-00964-x ORIGINAL RESEARCH ARTICLE Onapristone Extended Release: Safety Evaluation from Phase I–II Studies with an Emphasis on Hepatotoxicity James H. Lewis1 · Paul H. Cottu2 · Martin Lehr3 · Evan Dick3 · Todd Shearer3 · William Rencher3,4 · Alice S. Bexon5 · Mario Campone6 · Andrea Varga7 · Antoine Italiano8 © The Author(s) 2020 Abstract Introduction Antiprogestins have demonstrated promising activity against breast and gynecological cancers, but liver-related safety concerns limited the advancement of this therapeutic class. Onapristone is a full progesterone receptor antagonist originally developed as an oral contraceptive and later evaluated in phase II studies for metastatic breast cancer. Because of liver enzyme elevations identifed during clinical studies, further development was halted. Evaluation of antiprogestin pharmacology and pharmacokinetic data suggested that liver enzyme elevations might be related to of-target or metabolic efects associated with clinical drug exposure. Objective We explored whether the use of a pharmaceutic strategy targeting efcacious systemic dose concentrations, but with diminished peak serum concentrations and/or total drug exposure would mitigate hepatotoxicity. Twice-daily dosing of an extended-release formulation of onapristone was developed and clinically evaluated in light of renewed interest in antiprogestin therapy for treating progesterone receptor-positive breast and gynecologic cancers. The hepatotoxic potential of extended-release onapristone was assessed from two phase I–II studies involving patients with breast, ovarian, endometrial, and prostate cancer. Results Among the 88 patients in two phase I–II studies in progesterone receptor-positive malignancies treated with extended-release onapristone, elevated alanine aminotransferase/aspartate aminotransferase levels were found in 20% of patients with liver metastases compared with 6.3% without metastases.
    [Show full text]
  • Spontaneous Regression of an Asymptomatic Meningioma Associated with Discontinuation of Progesterone Agonist Administration —Case Report—
    Neurol Med Chir (Tokyo) 48, 227¿230, 2008 Spontaneous Regression of an Asymptomatic Meningioma Associated With Discontinuation of Progesterone Agonist Administration —Case Report— Jun SHIMIZU, Masayoshi MATSUMOTO, Etsuo YAMAZAKI*,andMasaharuYASUE Departments of Neurosurgery and *Radiology, Japanese Red Cross Hospital Ohmori, Tokyo Abstract An 80-year-old male visited the hospital as an outpatient with a head injury sustained in a traffic acci- dent. Brain computed tomography incidentally revealed a left frontal lobe tumor measuring 5 cm in a diameter. The patient had a history of taking chlormadinone acetate (a progesterone agonist) prescribed several years previously as treatment for benign prostatic hypertrophy. The tumor was seen as an isoin- tense lesion on T1-weighted magnetic resonance (MR) images with enhancement by gadolinium, and as a heterogeneously hyperintense mass on T2-weighted MR images. The tentative diagnosis was left fron- tal meningioma attached to the sphenoid ridge or sphenoid plane. The patient was managed conserva- tively because of his advanced age and no symptoms or progression were observed during a 9-month fol- low-up period. The medication for benign prostatic hypertrophy was changed from chlormadinone acetate to naftopidil (an alpha-2-blocker) about 9 months after his first presentation. The patient presented again 2 years later complaining of dizziness. Computed tomography and MR imaging per- formed at this time revealed remarkable regression of the tumor. The signal intensity change with regression of the tumor on T2-weighted images was observed as a hypointense lesion. Thus, we wish to emphasize that treatment of meningiomas, especially those diagnosed incidentally, must be based on a thorough consideration of any history of hormonal therapy with prostate disease.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • 2018 Medicines in Development for Cancer
    2018 Medicines in Development for Cancer Bladder Cancer Product Name Sponsor Indication Development Phase ABI-009 AADi Bioscience non-muscle invasive bladder cancer Phase I/II (nab-rapamycin/mTOR inhibitor) Los Angeles, CA www.aadibio.com ALT-801 Altor BioScience non-muscle invasive bladder cancer Phase I/II (tumor antigen-specific T-cell Miramar, FL www.altorbioscience.com receptor linked to IL-2) NantKwest Culver City, CA ALT-803 Altor BioScience non-muscle invasive bladder cancer Phase II (IL-15 superagonist protein complex) Miramar, FL (BCG naïve) (Fast Track), www.altorbioscience.com NantKwest non-muscle invasive bladder cancer Culver City, CA (BCG unresponsive) (Fast Track) B-701 BioClin Therapeutics 2L locally advanced or metastatic Phase I/II (anti-FGFR3 mAb) San Ramon, CA bladder cancer www.bioclintherapeutics.com Bavencio® EMD Serono 1L urothelial cancer Phase III avelumab Rockland, MA www.emdserono.com (anti-PD-L1 inhibitor) Pfizer www.pfizer.com New York, NY BC-819 BioCanCell Therapeutics non-muscle invasive bladder cancer Phase II (gene therapy) Cambridge, MA (Fast Track) www.biocancell.com Medicines in Development: Cancer ǀ 2018 1 Bladder Cancer Product Name Sponsor Indication Development Phase Capzola® Spectrum Pharmaceuticals non-muscle invasive bladder cancer application submitted apaziquone Henderson, NV (Fast Track) www.sppirx.com Cavatak® Viralytics bladder cancer (+pembrolizumab) Phase I coxsackievirus Sydney, Australia www.viralytics.com CG0070 Cold Genesys non-muscle invasive bladder cancer Phase II (oncolytic immunotherapy)
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0166583 A1 Zukiwski Et Al
    US 2016O166583A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0166583 A1 Zukiwski et al. (43) Pub. Date: Jun. 16, 2016 (54) ONAPRISTONE EXTENDED-RELEASE Publication Classification COMPOSITIONS AND METHODS (51) Int. Cl. (71) Applicant: ARNOTHERAPEUTICS, INC., A613 L/567 (2006.01) Flemington, NJ (US) A619/20 (2006.01) (52) U.S. Cl. (72) Inventors: Alexander Zukiwski, Clarksburg, MD CPC ................. A6 IK3I/567 (2013.01); A61 K9/20 (US); Stefan Proniuk, Austin, TX (US) (2013.01) (21) Appl. No.: 14/942,809 (57) ABSTRACT 1-1. Onapristone extended-release formulations and methods of (22) Filed: Nov. 16, 2015 administering onapristone extended-release formulations are O O provided. Onapristone extended-release formulations pro Related U.S. Application Data vide Sufficient therapeutic activity as compared to immediate (60) Provisional application No. 62/080,868, filed on Nov. release formulations with reduced potential for adverse side 17, 2014. effects. Patent Application Publication Jun. 16, 2016 Sheet 1 of 4 US 2016/O166583 A1 Figure Onapristone C vs Dose 7000 sood sood 4000 3ood 2000 338g .338g 388g ${}: 8:::::g it::g : & : & :: Patent Application Publication Jun. 16, 2016 Sheet 2 of 4 US 2016/O166583 A1 Figure 2 Onapristone AUC vs Dose 2300000 2000000 1sooooo 1000000 sooooo 88: it::gBreg $83.88ER 23rg E838E8 3rg 888 $g:::::::::::::::: 88 sig 8 1g:::::::: Patent Application Publication Jun. 16, 2016 Sheet 3 of 4 US 2016/O166583 A1 Figure 3 8 trig 8 it rig ER 28 ring £8 38 mg ER 48 trig ER 50 mg 88 .. 38 y 8 x 3y 38 83 y 3 Patent Application Publication Jun.
    [Show full text]
  • Methods of Contraception Verfahren Zur Empfängnisverhütung Methodes De Contraception
    Europäisches Patentamt *EP000792152B1* (19) European Patent Office Office européen des brevets (11) EP 0 792 152 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 31/565, A61P 15/18, of the grant of the patent: A61P 15/00 14.04.2004 Bulletin 2004/16 // (A61K31/565, 31:565) (21) Application number: 95940773.5 (86) International application number: PCT/US1995/015131 (22) Date of filing: 21.11.1995 (87) International publication number: WO 1996/015794 (30.05.1996 Gazette 1996/25) (54) METHODS OF CONTRACEPTION VERFAHREN ZUR EMPFÄNGNISVERHÜTUNG METHODES DE CONTRACEPTION (84) Designated Contracting States: (56) References cited: AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL EP-A- 0 659 432 WO-A-93/21926 PT SE WO-A-93/21927 WO-A-95/17194 WO-A-95/26730 (30) Priority: 22.11.1994 US 343383 • GUIAN CHEN, JUN RONG HUANG, JAMES (43) Date of publication of application: MAZELLA, LINDA TSENG: "Long-term effects of 03.09.1997 Bulletin 1997/36 progestin and RU 486 on prolactin and synthesis in human endometrial stromal cells" HUMAN (73) Proprietor: BALANCE PHARMACEUTICALS, INC. REPRODUCTION, vol. 4, no. 4, 1989, pages Pacific Palisades, CA 90272 (US) 355-358, XP000944177 • FERTILITY AND STERILITY, Vol. 53, No. 4, (72) Inventors: issued April 1990, KEKKONEN R. et al., • SPICER, Darcy V. "Interference With Ovulation by Sequential Pasadena, CA 91103 (US) Treatment With the Antiprogesterone RU486 and • PIKE, Malcolm Cecil Synthetic Progestin", pages 747-750, Long Beach, CA 90803 (US) XP000569448 • DANIELS, John R.
    [Show full text]
  • Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes
    Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABACAVIR 136470-78-5 ACEXAMIC ACID 57-08-9 ABAFUNGIN 129639-79-8 ACICLOVIR 59277-89-3 ABAMECTIN 65195-55-3 ACIFRAN 72420-38-3 ABANOQUIL 90402-40-7 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABIRATERONE 154229-19-3 ACIVICIN 42228-92-2 ABITESARTAN 137882-98-5 ACLANTATE 39633-62-0 ABLUKAST 96566-25-5 ACLARUBICIN 57576-44-0 ABUNIDAZOLE 91017-58-2 ACLATONIUM NAPADISILATE 55077-30-0 ACADESINE 2627-69-2 ACODAZOLE 79152-85-5 ACAMPROSATE 77337-76-9 ACONIAZIDE 13410-86-1 ACAPRAZINE 55485-20-6 ACOXATRINE 748-44-7 ACARBOSE 56180-94-0 ACREOZAST 123548-56-1 ACEBROCHOL 514-50-1 ACRIDOREX 47487-22-9 ACEBURIC ACID 26976-72-7
    [Show full text]
  • Antiprogestins in Breast Cancer Treatment: Are We Ready?
    Endocrine-Related Cancer (2012) 19 R35–R50 REVIEW Antiprogestins in breast cancer treatment: are we ready? Claudia Lanari, Victoria Wargon, Paola Rojas and Alfredo A Molinolo1 Instituto de Biologı´a y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina 1Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892-4340, USA (Correspondence should be addressed to A A Molinolo; Email: [email protected]) Abstract Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. It is accepted that breast cancer is not a single disease, but instead constitutes a spectrum of tumor subtypes with distinct cellular origins, somatic changes, and etiologies. Molecular gene expression studies have divided breast cancer into several categories, i.e. basal- like, ErbB2 enriched, normal breast-like (adipose tissue gene signature), luminal subtype A, luminal subtype B, and claudin-low. Chances are that as our knowledge increases, each of these types will also be subclassified. More than 66% of breast carcinomas express estrogen receptor alpha (ERa) and respond to antiestrogen therapies. Most of these ERC tumors also express progesterone receptors (PRs), the expression of which has been considered as a reliable marker of a functional ER. In this paper we will review the evidence suggesting that PRs are valid targets for breast cancer therapy. Experimental data suggest that both PR isoforms (A and B) have different roles in breast cancer cell growth, and antiprogestins have already been clinically used in patients who have failed to other therapies. We hypothesize that antiprogestin therapy may be suitable for patients with high levels of PR-A.
    [Show full text]