Gonadotropin-Releasing Hormone Antagonists Versus Standard Androgen Suppression Therapy for Advanced Prostate Cancer a Systematic Review with Meta-Analysis

Total Page:16

File Type:pdf, Size:1020Kb

Gonadotropin-Releasing Hormone Antagonists Versus Standard Androgen Suppression Therapy for Advanced Prostate Cancer a Systematic Review with Meta-Analysis Open Access Research BMJ Open: first published as 10.1136/bmjopen-2015-008217 on 13 November 2015. Downloaded from Gonadotropin-releasing hormone antagonists versus standard androgen suppression therapy for advanced prostate cancer A systematic review with meta-analysis Frank Kunath,1,2 Hendrik Borgmann,2,3 Anette Blümle,4 Bastian Keck,1 Bernd Wullich,1,2 Christine Schmucker,4 Danijel Sikic,1 Catharina Roelle,1 Stefanie Schmidt,2 Amr Wahba,5 Joerg J Meerpohl4 To cite: Kunath F, ABSTRACT et al Strengths and limitations of this study Borgmann H, Blümle A, . Objectives: To evaluate efficacy and safety of Gonadotropin-releasing gonadotropin-releasing hormone (GnRH) antagonists ▪ hormone antagonists versus We searched CENTRAL, MEDLINE, Web of compared to standard androgen suppression therapy standard androgen Science, EMBASE, trial registries and conference suppression therapy for for advanced prostate cancer. books. Two authors independently screened advanced prostate cancer A Setting: The international review team included identified articles, extracted data, evaluated risk systematic review with meta- methodologists of the German Cochrane Centre and of bias and rated quality of evidence according analysis. BMJ Open 2015;5: clinical experts. to GRADE. e008217. doi:10.1136/ Participants: We searched CENTRAL, MEDLINE, Web ▪ There were no statistically significant differences bmjopen-2015-008217 of Science, EMBASE, trial registries and conference in overall mortality, treatment failure, or prostate- books for randomised controlled trials (RCT) for specific antigen progression and no study ▸ Prepublication history for effectiveness data analysis, and randomised or non- reported cancer-specific survival or clinical this paper is available online. randomised controlled studies (non-RCT) for safety progression. To view these files please data analysis (March 2015). Two authors ▪ Quality of evidence for all assessed outcomes visit the journal online independently screened identified articles, extracted was rated low according to GRADE. Available evi- (http://dx.doi.org/10.1136/ data, evaluated risk of bias and rated quality of dence is hampered by risk of bias, selective http://bmjopen.bmj.com/ bmjopen-2015-008217). evidence according to GRADE. reporting and limited follow-up. ▪ Received 10 May 2015 Results: 13 studies (10 RCTs, 3 non-RCTs) were The question that was addressed by this system- Revised 12 September 2015 included. No study reported cancer-specific survival atic review was in some points different from the Accepted 9 October 2015 or clinical progression. There were no differences in available evidence. There is currently insufficient overall mortality (RR 1.35, 95% CI 0.63 to 2.93), evidence to make firm conclusive statements on treatment failure (RR 0.91, 95% CI 0.70 to 1.17) or the efficacy of GnRH antagonist compared to prostate-specific antigen progression (RR 0.83, 95% standard androgen suppression therapy for CI 0.64 to 1.06). While there was no difference in advanced prostate cancer and there is a need for quality of life related to urinary symptoms, improved further high quality research on GnRH antago- on October 1, 2021 by guest. Protected copyright. quality of life regarding prostate symptoms, measured nists with long-term follow-up. with the International Prostate Symptom Score (IPSS), with the use of GnRH antagonists compared with the use of standard androgen suppression There is need for further high-quality research on therapy (mean score difference −0.40, 95% CI −0.94 GnRH antagonists with long-term follow-up. to 0.14, and −1.84, 95% CI −3.00 to −0.69, Trial registration number: CRD42012002751. respectively) was found. Quality of evidence for all assessed outcomes was rated low according to GRADE. The risk for injection-site events was increased, but cardiovascular events may occur less INTRODUCTION often by using GnRH antagonist. Available evidence is For numbered affiliations see hampered by risk of bias, selective reporting and Gonadotropin-releasing hormone (GnRH) end of article. limited follow-up. antagonists, such as abarelix or degarelix, are Conclusions: There is currently insufficient evidence new agents for androgen suppression therapy Correspondence to to make firm conclusive statements on the efficacy of in advanced prostate cancer. They act by Dr Frank Kunath; frank. GnRH antagonist compared to standard androgen competitively binding to receptors in the [email protected] suppression therapy for advanced prostate cancer. pituitary gland, leading to reduced amounts Kunath F, et al. BMJ Open 2015;5:e008217. doi:10.1136/bmjopen-2015-008217 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2015-008217 on 13 November 2015. Downloaded from of luteinising hormone and follicle-stimulating advanced (T3-4, N0, M0), local to regionally advanced hormone. GnRH antagonists are, thereby, able to (T1-4, N1, M0), disseminated disease (T1-4, N0-1, M1) decrease the level of testosterone immediately to castra- or PSA relapse after local therapy. – tion levels without flare.1 3 Testosterone is important for Included studies had to compare GnRH antagonists the growth of prostate cells and its suppression slows (abarelix or degarelix) with standard androgen suppres- down the disease progression and leads to a decrease in sion. The standard androgen suppression therapy prostate-specific antigen (PSA). included monotherapy with surgical or medical castra- Data from published randomised controlled trials tion, antiandrogen monotherapy or maximal androgen support the use of degarelix as an alternative to standard blockade (combination of either surgical or medical cas- androgen suppression therapies.45Abarelix appears to tration with antiandrogens). be equally effective.26Androgen suppression therapy Our prospectively defined primary outcomes were with degarelix may also be more cost-effective in patients overall survival and adverse events. We defined cancer- – with locally advanced prostate cancer7 9 and may specific survival, clinical or PSA progression, treatment increase PSA progression-free and overall survival.510 failure and quality of life as secondary outcomes. No Additionally, degarelix might also have beneficial effects study was excluded solely because the outcome of inter- on lower urinary tract symptoms.11 Furthermore, GnRH est was not reported. antagonists might provide an alternative to castration in Unit of analysis was the study rather than publications, symptomatic patients with advanced prostate cancer and we named the studies according to their study iden- because there is no risk for testosterone flare associated tification numbers assigned by the sponsors. We used with GnRH agonists that might aggravate clinical symp- the sponsors identification numbers for differentiation toms.12 Despite these positive findings, the current because several authors were involved in more than one European guideline indicate that there is no definitive study, publications were identified reporting information evidence that GnRH antagonists have advantages over on several studies (pooled analyses of individual patient GnRH agonists.13 data of five randomised controlled trials: CS21, CS28, An analysis of pooled individual patient data of five CS30, CS31, CS35), and as there were several publica- randomised clinical trials found clinical benefits with tions available for some studies (eg, different follow-up degarelix compared with GnRH agonists.10 However, no time or reporting different outcomes). systematic review based on a comprehensive literature We searched the Cochrane Library (CENTRAL, Issue search using predefined methodology have yet evaluated 3, 2015), MEDLINE (via Ovid; 1946 to March 2015), the efficacy and tolerability of GnRH antagonists in com- Web of Science (Thomson Reuters Web of Knowledge; parison with standard androgen suppression therapy for 1970 to March 2015), and EMBASE (via DIMDI; 1947 to advanced prostate cancer. Therefore, the objectives of March 2015) databases. For details on the search strat- this systematic review are to determine the efficacy and egy, see table 1. safety of GnRH antagonists compared with standard Additionally, we searched three trial registries: Current http://bmjopen.bmj.com/ androgen suppression therapy for advanced prostate Controlled Trials (ISRCTN; http://www.controlled-trials. cancer treatment. com/; last search in March 2015), ClinicalTrials.gov (http://www.clinicaltrials.gov/; last search in March 2015), and the WHO International Clinical Trials METHODS Registry Platform Search Portal (WHO ICTRP Search For details on our predefined methodology and Portal; http://www.who.int/ictrp/en/; last search in outcomes see the prospective registry entry in the March 2015). We used the following keywords for this ‘International Prospective Register of Systematic search: ‘abarelix’, ‘degarelix’, ‘plenaxis’, ‘firmagon’. on October 1, 2021 by guest. Protected copyright. Reviews’ (http://www.crd.york.ac.uk/PROSPERO;CRD We also searched the electronically available abstract 42012002751). books from three major conferences: American Society We included studies that compared GnRH antagonists of Clinical Oncology (ASCO; jco.ascopubs.org; 2004 to (abarelix and degarelix) with standard androgen sup- March 2015), European Association of Urology (EAU; pression therapy in patients with advanced prostate http://www.uroweb.org; 2004 to March 2015), and cancer. Included studies had to be randomised con- American Urological Association (AUA; http://www. trolled trials (that were used for efficacy
Recommended publications
  • CASODEX (Bicalutamide)
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Gynecomastia and breast pain have been reported during treatment with These highlights do not include all the information needed to use CASODEX 150 mg when used as a single agent. (5.3) CASODEX® safely and effectively. See full prescribing information for • CASODEX is used in combination with an LHRH agonist. LHRH CASODEX. agonists have been shown to cause a reduction in glucose tolerance in CASODEX® (bicalutamide) tablet, for oral use males. Consideration should be given to monitoring blood glucose in Initial U.S. Approval: 1995 patients receiving CASODEX in combination with LHRH agonists. (5.4) -------------------------- RECENT MAJOR CHANGES -------------------------- • Monitoring Prostate Specific Antigen (PSA) is recommended. Evaluate Warnings and Precautions (5.2) 10/2017 for clinical progression if PSA increases. (5.5) --------------------------- INDICATIONS AND USAGE -------------------------- ------------------------------ ADVERSE REACTIONS ----------------------------- • CASODEX 50 mg is an androgen receptor inhibitor indicated for use in Adverse reactions that occurred in more than 10% of patients receiving combination therapy with a luteinizing hormone-releasing hormone CASODEX plus an LHRH-A were: hot flashes, pain (including general, back, (LHRH) analog for the treatment of Stage D2 metastatic carcinoma of pelvic and abdominal), asthenia, constipation, infection, nausea, peripheral the prostate. (1) edema, dyspnea, diarrhea, hematuria, nocturia, and anemia. (6.1) • CASODEX 150 mg daily is not approved for use alone or with other treatments. (1) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca Pharmaceuticals LP at 1-800-236-9933 or FDA at 1-800-FDA-1088 or ---------------------- DOSAGE AND ADMINISTRATION ---------------------- www.fda.gov/medwatch The recommended dose for CASODEX therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening).
    [Show full text]
  • LHRH) Antagonist Cetrorelix and LHRH Agonist Triptorelin on the Gene Expression of Pituitary LHRH Receptors in Rats
    Comparison of mechanisms of action of luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix and LHRH agonist triptorelin on the gene expression of pituitary LHRH receptors in rats Magdolna Kovacs*†‡ and Andrew V. Schally*†§ *Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70112; and †Section of Experimental Medicine, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112 Contributed by Andrew V. Schally, August 21, 2001 The mechanisms through which luteinizing hormone (LH)-releasing however, are different. LHRH agonists achieve the inhibition of hormone (LHRH) antagonists suppress pituitary gonadotroph func- gonadotropin secretion after a period of continuous exposure (1, tions and LHRH-receptor (LHRH-R) expression are incompletely un- 2, 11–14). In contrast, antagonists of LHRH produce a compet- derstood. Consequently, we investigated the direct effect of LHRH itive blockade of LHRH-R and cause an immediate cessation of antagonist cetrorelix in vitro on the expression of the pituitary the release of gonadotropins and sex steroids, reducing the time LHRH-R gene and its ability to counteract the exogenous LHRH and of the onset of therapeutic effects as compared with the agonists the agonist triptorelin in the regulation of this gene. We also com- (1, 2, 15–17). LHRH agonists such as triptorelin, leuprolide, pared the effects of chronic administration of cetrorelix and triptore- buserelin, or goserelin (1, 2, 14) have been used worldwide for lin on the LHRH-R mRNA level and gonadotropin secretion in ovari- nearly two decades, but LHRH antagonists such as cetrorelix, ectomized (OVX) and normal female rats. The exposure of pituitary ganirelix, and Abarelix have been introduced into the clinical cells in vitro to 3-min pulses of 1 nM LHRH or 0.1 nM triptorelin for 5 h practice relatively recently (1, 2, 15, 16).
    [Show full text]
  • Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals
    Journal of Clinical Medicine Review Hormonal Treatment Strategies Tailored to Non-Binary Transgender Individuals Carlotta Cocchetti 1, Jiska Ristori 1, Alessia Romani 1, Mario Maggi 2 and Alessandra Daphne Fisher 1,* 1 Andrology, Women’s Endocrinology and Gender Incongruence Unit, Florence University Hospital, 50139 Florence, Italy; [email protected] (C.C); jiska.ristori@unifi.it (J.R.); [email protected] (A.R.) 2 Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, 50139 Florence, Italy; [email protected]fi.it * Correspondence: fi[email protected] Received: 16 April 2020; Accepted: 18 May 2020; Published: 26 May 2020 Abstract: Introduction: To date no standardized hormonal treatment protocols for non-binary transgender individuals have been described in the literature and there is a lack of data regarding their efficacy and safety. Objectives: To suggest possible treatment strategies for non-binary transgender individuals with non-standardized requests and to emphasize the importance of a personalized clinical approach. Methods: A narrative review of pertinent literature on gender-affirming hormonal treatment in transgender persons was performed using PubMed. Results: New hormonal treatment regimens outside those reported in current guidelines should be considered for non-binary transgender individuals, in order to improve psychological well-being and quality of life. In the present review we suggested the use of hormonal and non-hormonal compounds, which—based on their mechanism of action—could be used in these cases depending on clients’ requests. Conclusion: Requests for an individualized hormonal treatment in non-binary transgender individuals represent a future challenge for professionals managing transgender health care. For each case, clinicians should balance the benefits and risks of a personalized non-standardized treatment, actively involving the person in decisions regarding hormonal treatment.
    [Show full text]
  • Personalized ADT
    Personalized ADT Thomas Keane MD Conflicts • Ferring • Tolemar • Bayer • Astellas • myriad Personalized ADT for the Specific Paent • Cardiac • OBesity and testosterone • Fsh • High volume metastac disease • Docetaxol • Significant LUTS Cardiovascular risk profile and ADT Is there a difference? Degarelix Belongs to a class of synthe@c drug, GnRH antagonist (Blocker) GnRH pGlu His Trp Ser Tyr Gly Leu Arg Pro Gly NH2 Leuprolide D-Leu NEt Goserelin D-Ser NH2 LHRH agonists Triptorelin D-Trp NH2 Buserelin D-Ser NEt Degarelix D-NaI D-Cpa D-PaI Aph D-Aph D-Ala NH2 N-Me ABarelix D-NaI D-Cpa D-PaI D-Asn Lys D-Ala NH2 Tyr GnRH antagonists Cetrorelix D-NaI D-Cpa D-PaI D-Cit D-Ala NH2 Ganirelix D-NaI D-CPa D-PaI D-hArg D-hArg D-Ala NH2 Millar RP, et al. Endocr Rev 2004;25:235–75 Most acute CVD events are caused By rupture of a vulnerable atherosclero@c plaque The vulnerable plaque – thin cap with inflammaon Inflammation Plaque instability is at the heart of cardiovascular disease Stable plaque Vulnerable plaque Lumen Lumen Lipid core Lipid core FiBrous cap FiBrous cap Thick Cap Thin Rich in SMC and matrix Composion Rich in inflammatory cells: proteoly@c ac@vity Poor Lipid Rich Inflammatory Inflammatory state Highly inflammatory LiBBy P. Circulaon 1995;91:2844-2850 Incidence of Both prostate cancer and CV events is highest in older men Prostate cancer CV events 3500 3500 Prostate cancer All CV disease Major CV events 3000 3000 2827.1 2500 2500 2338.9 2000 2000 1719.7 1500 1500 1152.6 1008.7 1038.7 1000 1000 641.2 545.2 571.1 Age-specific incidence per 100,000 person-years 500 500 246.9 133.7 4.3 0 0 40-49 50-59 60-69 70-79 80-89 90-99 40-49 50-59 60-69 70-79 80-89 90-99 CV, cardiovascular Major CV events = myocardial infarc@on, stroke, or death due to CV disease All CV disease = major CV events + self-reported angina or revascularisaon procedures Driver, et al.
    [Show full text]
  • Hertfordshire Medicines Management Committee (Hmmc) Nafarelin for Endometriosis Amber Initiation – Recommended for Restricted Use
    HERTFORDSHIRE MEDICINES MANAGEMENT COMMITTEE (HMMC) NAFARELIN FOR ENDOMETRIOSIS AMBER INITIATION – RECOMMENDED FOR RESTRICTED USE Name: What it is Indication Date Decision NICE / SMC generic decision status Guidance (trade) last revised Nafarelin A potent agonistic The hormonal December Final NICE NG73 2mg/ml analogue of management of 2020 Nasal Spray gonadotrophin endometriosis, (Synarel®) releasing hormone including pain relief and (GnRH) reduction of endometriotic lesions HMMC recommendation: Amber initiation across Hertfordshire (i.e. suitable for primary care prescribing after specialist initiation) as an option in endometriosis Background Information: Gonadorelin analogues (or gonadotrophin-releasing hormone agonists [GnRHas]) include buserelin, goserelin, leuprorelin, nafarelin and triptorelin. The current HMMC decision recommends triptorelin as Decapeptyl SR® injection as the gonadorelin analogue of choice within licensed indications (which include endometriosis) link to decision. A request was made by ENHT to use nafarelin nasal spray as an alternative to triptorelin intramuscular injection during the COVID-19 pandemic. The hospital would provide initial 1 month supply, then GPs would continue for further 5 months as an alternative to the patient attending for further clinic appointments for administration of triptorelin. Previously at ENHT, triptorelin was the only gonadorelin analogue on formulary for gynaecological indications. At WHHT buserelin nasal spray 150mcg/dose is RED (hospital only) for infertility & endometriosis indications. Nafarelin nasal spray 2mg/ml is licensed for: . The hormonal management of endometriosis, including pain relief and reduction of endometriotic lesions. Use in controlled ovarian stimulation programmes prior to in-vitro fertilisation, under the supervision of an infertility specialist. Use of nafarelin in endometriosis aims to induce chronic pituitary desensitisation, which gives a menopause-like state maintained over many months.
    [Show full text]
  • Degarelix for Treating Advanced Hormone- Dependent Prostate Cancer
    CONFIDENTIAL UNTIL PUBLISHED NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Final appraisal determination Degarelix for treating advanced hormone- dependent prostate cancer This guidance was developed using the single technology appraisal (STA) process 1 Guidance 1.1 Degarelix is recommended as an option for treating advanced hormone-dependent prostate cancer, only in adults with spinal metastases who present with signs or symptoms of spinal cord compression. 1.2 People currently receiving treatment initiated within the NHS with degarelix that is not recommended for them by NICE in this guidance should be able to continue treatment until they and their NHS clinician consider it appropriate to stop. 2 The technology 2.1 Degarelix (Firmagon, Ferring Pharmaceuticals) is a selective gonadotrophin-releasing hormone antagonist that reduces the release of gonadotrophins by the pituitary, which in turn reduces the secretion of testosterone by the testes. Gonadotrophin- releasing hormone is also known as luteinising hormone-releasing hormone (LHRH). Because gonadotrophin-releasing hormone antagonists do not produce a rise in hormone levels at the start of treatment, there is no initial testosterone surge or tumour stimulation, and therefore no potential for symptomatic flares. National Institute for Health and Care Excellence Page 1 of 71 Final appraisal determination – Degarelix for treating advanced hormone-dependent prostate cancer Issue date: April 2014 CONFIDENTIAL UNTIL PUBLISHED Degarelix has a UK marketing authorisation for the ‘treatment of adult male patients with advanced hormone-dependent prostate cancer’. It is administered as a subcutaneous injection. 2.2 The most common adverse reactions with degarelix are related to the effects of testosterone suppression, including hot flushes and weight increase, or injection site reactions (such as pain and erythema).
    [Show full text]
  • Altered Cognitive Function in Men Treated for Prostate
    Altered Cognitive Function in Men Treated for Prostate Cancer with LHRH Analogues and Cyproterone Acetate: A Randomised Controlled Trial H. J. Green PhD1,2, K. I. Pakenham PhD1, B. C. Headley PhD3, J. Yaxley FRACS3, D. L. Nicol FRACS2,4, P. N. Mactaggart FRACS2,5, C. Swanson PhD2, R. B. W atson FRACS6, & R. A. Gardiner MD2,3 1School of Psychology and 2Department of Surgery, The University of Queensland, 3Royal Brisbane, 4Princess Alexandra, 5Queen Elizabeth II & 6Mater Hospitals, Brisbane, Queensland, Australia In conjunction with the Northern Section of the Urological Society of Australasia Correspondence should be addressed to: Dr R. A. Gardiner, Department of Surgery, The University of Queensland, Brisbane, Qld 4072, Australia Fax: +61 7 3365 5559; Phone: +61 7 3365 5233; Email: f.gardiner@ mailbox.uq.edu.au This work was wholly funded by Queensland Cancer Fund. **PREPRINT. Final version published in British Journal of Urology (BJU: International) (2002), 90, 427-432 ** Short Title: COGNITIVE CHANGES W ITH HORMONAL MEDICATION 2 Objective. Luteinising hormone releasing hormone (LHRH) analogues have been associated with memory impairments in women using these drugs for gynaecological conditions. This is the first systematic investigation of the cognitive effects of LHRH analogues in male patients. Methods. 82 men with non-localised prostate cancer were randomly assigned to receive continuous leuprorelin (LHRH analogue), goserelin (LHRH analogue), cyproterone acetate (steroidal antiandrogen) or close clinical monitoring. These patients underwent cognitive assessments at baseline and before commencement of treatment (77) then 6 months later (65). Results. Compared with baseline assessments, men administered androgen suppression monotherapy performed worse in 2/12 tests of attention and memory.
    [Show full text]
  • Degarelix Acetate (Firmagon) Reference Number: PA.CP.PHAR.170 Effective Date: 01/18 Last Review Date: 10/18 Revision Log
    Clinical Policy: Degarelix Acetate (Firmagon) Reference Number: PA.CP.PHAR.170 Effective Date: 01/18 Last Review Date: 10/18 Revision Log Description The intent of the criteria is to ensure that patients follow selection elements established by Pennsylvania Health and Wellness® clinical policy for the use of Degarelix Acetate (Firmagon®). FDA Approved Indication(s) Firmagon is indicated for treatment of advanced prostate cancer. Policy/Criteria It is the policy of Pennsylvania Health and Wellness that Firmagon is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Prostate Cancer (must meet all): 1. Diagnosis of prostate cancer; 2. Prescribed by or in consultation with an oncologist; 3. Request meets one of the following (a, b or c): a. Starting dose does not exceed 240 mg given as two injections of 120 mg each; b. Maintenance dose does not exceed 80 mg as a single injection per 28 days; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off- label use (prescriber must submit supporting evidence). Approval duration: 12 months B. Other diagnoses/indications: Refer to PA.CP.PMN.53 1. The following NCCN recommended uses for Firmagon, meeting NCCN categories 1, 2a, or 2b, are approved per the PA.CP.PMN.53: II. Continued Approval A. Prostate Cancer (must meet all): 1. Currently receiving medication via Pennsylvania Health and Wellness benefit or member has previously met approval criteria or the Continuity of Care policy (PA.LTSS.PHAR.01) applies; 2. Member is responding positively to therapy; 3. If request is for a dose increase, request meets one of the following: a.
    [Show full text]
  • Goserelin (Zoladex)
    Goserelin (Zoladex) This booklet explains what goserelin is, when it may be prescribed, how it works and what side effects may occur. Goserelin is the generic (non‑branded) name of the drug and how it’s referred to in this booklet. Its current brand name is Zoladex. This information is by Breast Cancer Care. We are the only specialist UK‑wide charity that supports people affected by breast cancer. We’ve been supporting them, their family and friends and campaigning on their behalf since 1973. Today, we continue to offer reliable information and personal support, over the phone and online, from nurses and people who’ve been there. We also offer local support across the UK. From the moment you notice something isn’t right, through to treatment and beyond, we’re here to help you feel more in control. For breast cancer care, support and information, call us free on 0808 800 6000 or visit breastcancercare.org.uk Visit breastcancercare.org.uk 3 What is goserelin? Goserelin is a type of hormone therapy used to treat breast cancer in pre-menopausal women (women who have not been through the menopause). It is given as an injection into the abdomen (belly). It can also be used to try to preserve fertility during chemotherapy (see page 4). Goserelin as a treatment for breast cancer How does it work? Some breast cancers are stimulated to grow by the hormone oestrogen. Before the menopause, oestrogen is mainly produced in the ovaries. Goserelin switches off this production by interfering with hormone signals from the brain that control how the ovaries work.
    [Show full text]
  • Triptorelin, Goserelin and Leuprorelin for Prostate
    789FM.1 GONADORELIN ANALOGUES (GnRHa): TRIPTORELIN, GOSERELIN, LEUPRORELIN FOR PROSTATE CANCER - AMBER RECOMMENDATION GUIDELINE This guideline provides prescribing and monitoring guidance for triptorelin, goserelin and Leuprorelin use in prostate cancer. It should be read in conjunction with the Summary of Product Characteristics (SPC), available on www.medicines.org.uk/emc, and the BNF. BACKGROUND AND INDICATIONS FOR USE There is no conclusive evidence to suggest that any one GnRHa is more effective or has fewer side effects than another for the treatment of prostate cancer.5, 7-9 Available evidence suggests that GnRHa are similar in effectiveness to surgical castration. They have the same licensed indications in the treatment of prostate cancer (Appendix 1). Appendix 2 compares doses, administration frequency and costs.1-4, 9-13 Triptorelin 22.5 mg (six monthly injection) is the 1st choice GnRHa for treatment of metastatic prostate cancer patients on life-long treatment on the Bucks formulary. This is because it is: • Administered via a smaller sized needle (20 gauge) compared to goserelin LA 10.8 mg (14 gauge), thus minimising discomfort to patients.9 • The least expensive in terms of drug and administration costs (Appendix 2).1-4, 9-13 Triptorelin 22.5 mg (six monthly injection) is not preferred in: • Patients newly initiated GnRHa because the first dose should be a monthly preparation (Decapeptyl® SR 3 mg) in order to check that the product is tolerated prior to changing to the six monthly preparation.14 • Anticoagulated patients. This is because triptorelin is an intramuscular (IM) injection. Subcutaneously administered GnRHa (goserelin or leuprorelin) may be preferable.9 RESPONSIBILITIES Hospital specialist 1.
    [Show full text]
  • Follicular and Endocrine Profiles Associated with Different Gnrh
    Reproductive BioMedicine Online (2012) 24, 153– 162 www.sciencedirect.com www.rbmonline.com ARTICLE Follicular and endocrine profiles associated with different GnRH-antagonist regimens: a randomized controlled trial Juan Antonio Garcı´a-Velasco a, Sanja Kupesic b, Antonio Pellicer c, Claire Bourgain d, Carlos Simo´n e, Milan Mrazek f, Paul Devroey g, Joan-Carles Arce h,* a IVI Foundation, Reproductive Endocrinology, Madrid, Spain; b Texas Tech University Health Sciences Center, Department of Obstetrics and Gynecology, El Paso, TX, USA; c IVI Foundation, Reproductive Endocrinology, Valencia, Spain; d UZ Brussel, Department of Pathology, Brussels, Belgium; e IVI Foundation, Research Department, Valencia, Spain; f ISCARE IVF a.s., Lighthouse, Prague, Czech Republic; g UZ Brussel, Centre for Reproductive Medicine, Brussels, Belgium; h Reproductive Health, Global Clinical and Non-Clinical R & D, Ferring Pharmaceuticals, Copenhagen, Denmark * Corresponding author. E-mail address: [email protected] (J.-C. Arce). Dr Juan Garcı´a-Velasco did his training in obstetrics and gynaecology at Madrid Autonoma University, and then his reproductive endocrinology and infertility fellowship at Yale University, USA (1997–1998). He is now Director of IVI-Madrid and Associate Professor at Rey Juan Carlos University. He has published over 100 peer- reviewed articles. He is an ad-hoc reviewer for the main journals in the field and serves on the editorial board of Reproductive BioMedicine Online. His main research interests are endometriosis, ovarian hyperstimulation syndrome, low responders and human implantation. Abstract This trial assessed the impact of early initiation of gonadotrophin-releasing hormone (GnRH) antagonist on follicular and endocrine profiles compared with the fixed GnRH-antagonist protocol.
    [Show full text]
  • Gnrh Antagonists Have Direct Inhibitory Effects on Castration-Resistant Prostate
    Author Manuscript Published OnlineFirst on July 24, 2019; DOI: 10.1158/1535-7163.MCT-18-1337 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. GnRH antagonists have direct inhibitory effects on castration-resistant prostate cancer via intracrine androgen and AR-V7 expression. Vito Cucchiara1*, Joy C. Yang1*, Chengfei Liu1, Hans H. Adomat2, Emma S. Tomlinson Guns2, Martin E. Gleave2, Allen C. Gao1,3, Christopher P. Evans1,3 1Department of Urologic Surgery, University of California at Davis, Sacramento, California. 2Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada 3UC Davis Comprehensive Cancer Center, University of California Davis, California. Running title: GnRH antagonist inhibits intracrine androgen and AR-V7 Keywords: Prostate Cancer, ADT, GnRH antagonist, intracrine androgen Financial Support: This work is supported in part by grants DOD PC150040P1 and Ferring Pharmaceuticals to CP Evans. Conflicts of Interest: Research support from Ferring to CPE and JCY. All other authors have no conflicts of interest. Corresponding Author: Christopher P. Evans, MD, FACS Professor and Chairman, Department of Urology Urologic Surgical Oncology University of California, Davis, School of Medicine 4860 Y St., Suite 3500 Sacramento, CA 95817 academic office tel # (916)734-7520 academic office fax # (916)734-8094 email: [email protected] *These authors contributed equally to this work Downloaded from mct.aacrjournals.org on October 6, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on July 24, 2019; DOI: 10.1158/1535-7163.MCT-18-1337 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
    [Show full text]