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Aspects of the Usage of Antineoplastic and 1Mmunomodulating Agents in a Section of the Private Health Care Sector

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ASPECTS OF THE USAGE OF ANTINEOPLASTIC AND 1MMUNOMODULATING AGENTS IN A SECTION OF THE PRIVATE HEALTH CARE SECTOR Wilmarie Rheeders B. Pharm Dissertation submitted in Pharmacy Practice, School of Pharmacy at the Faculty of Health Sciences of the North-West University, Potchefstroom, in partial fulfilment of the requirements for the degree Magister Pharmaciae. Supervisor: Prof M.S. Lubbe Co-supervisor: Dr. J.L. Duminy Co-supervisor: Prof. M.P. Stander Potchefstroom November 2008 For all things are from Him, by Him, and for Him. Glory belongs to Him forever! Amen. (Rom. 11:36) ACKNOWLEDGEMENTS To my Lord and Father whom I love, all the Glory! He gave me the strength, insight and endurance to finish this study. 1 also want to express my sincere appreciation to the following people that have contributed to this dissertation: • To Professor M.S. Lubbe, in her capacity as supervisor of this dissertation, my appreciation for her expert supervision, advice and time she invested in this study. • To Dr. J.L Duminy, oncologist and co-supervisor, for all the useful advice, assistance and time he put aside in the interest of this dissertation. • To Professor M.P. Stander, in his capacity as co-supervisor of this study. • To Professor J.H.P. Serfontein, for his guidance, time, effort and advice. • To the Department of Pharmacy Practice as well as the NRF for the technical and financial support. • To Anne-Marie, thank you for your patience, time and continuous effort you put into the data. • To the Pharmacy Benefit Management company for providing the data for this dissertation. • To Mrs. Elma de Kockforthe language editing of this study. • To Prof. Casper Lessing for the editing of the bibliography of this study. • To my parents, Gert and Mariaan Breed - no words can express my gratitude, love and respect. Thank you for your faith in me and your support, encouragement and especially your prayers throughout my studies. • To my dear brother, Marnus, who was in a serious car accident in June 2008 - the strength, perseverance and optimism with which you live your life encouraged me to give my best. You are always in my prayers. • To my big brother, Gerbrand and sister-in-law, Melissa - thank you for your love, support and encouragement. • To my husband, Danie - your love, continuous encouragement and never- ending faith in me has helped me through - you mean the world to me. I love you. • To my family-in-law, thank you for your support. • To my housemates and dear friends, Adri and Rinee - for their friendship, support, encouragement, patience and for listening, every time. • To my friend Eugene, thank you for your loyal friendship, support, encouragement and all the coffees. • To all my friends for their continuous support and friendship. • To my fellow M-students, especially Anri, Corlee, Jenine, Mariet, Rial and Ulrich for their support, encouragement and friendship. ABSTRACT Title: Aspects of the usage of antineoplastic and immunomodulating agents in a section of the private health care sector. Keywords: Cancer, antineoplastic and immunomodulating agents, cancer medicine items, cancer treatment, pharmacoeconomics, cost of cancer. Cancer is a broad term used to describe more than 100 diseases that can affect any part of the body. Cancer is the uncontrollable division of abnormal cells in the human body, which can invade nearby tissue and spread through the bloodstream to other parts of the body (National Cancer Institute, 2007b). Cancer can affect people all over the world, from every race, society and age (Albrecht, 2006:3). The treatment of cancer is becoming more and more expensive as newer and more effective drugs enter the market (Niezen et al., 2006:2887) and diagnosing and screening of cancer patients is showing remarkable progress (Meropol & Schulman, 2007:180). The general objective of this study was to investigate and review the prescribing patterns of antineoplastic and immunomodulating agents in a section of the private health care sector of South Africa. This research can be classified as retrospective and quantitative. Data were obtained from a medicine claims database, of a pharmacy benefit management company. The study population consisted of all prescriptions, containing one or more cancer medicine items (classified according to the ATC classification), for the study period January 2005 to December 2006. Different aspects of cancer were investigated in order to determine the international and national prevalence of cancer and types of cancer and cancer treatment. An overview of managed care aspects were given and through this study it is evident that pharmacoeconomic studies and other managed care aspects could play a major role as information system in the decision making about cancer treatments. The prescribing patterns of antineoplastic and immunomodulating agents were reviewed, analysed and interpreted. It was determined that the number of cancer patients, the number of prescriptions containing one of more cancer drug and the number of cancer medicine items respectively comprised less than 1% of the total Abstract number of patients, prescriptions and medicine items recorded on the total database. To the contrary, the total cost of cancer medicine items comprised 4.00% and 5.31% of the total cost of all medicine items (total database) in 2005 and 2006 respectively. This indicates the relatively high cost of cancer medicine items. Almost 50% of all cancer patients are 59 years of age or older and the total cost of cancer medicine items claimed by patients 59 years and older comprised almost 60% of the total cost of all cancer medicine items claimed during the two study years respectively. Cancer medicine items claimed by patients <19 years of age comprised only 2% of all cancer medicine items claimed in both study years and less than 1% of the total cost of all cancer medicine items. Cancer medicine items claimed by patients between the age of 19 and 59 years of age comprised 45.32% and 44.80% of the total number of cancer medicine items in 2005 and 2006 respectively whilst the cost for these age groups comprised 40.81% and 40.73% of the total cost of cancer medicine items. More than 70% of all cancer patients in 2005 and 2006 were females whilst male cancer patients comprised about 30% of all cancer patients. The number of cancer medicine items claimed by female cancer patients also comprised more than 70% of the total number of cancer medicine items claimed in 2005 and 2006, however, the total cost of cancer medicine items was divided almost even between male (45%) and female (55%) cancer patients for both study years. Therefore, according to this study, cancer medicine items claimed by male cancer patients are relatively more expensive than those claimed by female cancer patients. In completion of this study, recommendations for further studies concerning cancer treatment and cost-effective usage of cancer medicine were formulated, including the influence of the nature of the cancer, the age and gender of the patients as well as the treatment costs of cancer. OPSOMMING Titel: Aspekte van die gebruik van antineoplastiese en immunomodulerende agente in 'n deel van die privaat-gesondheidsorgsektor. Sleutelwoorde: Kanker, antineoplastiese en immunomodulerende agente, kanker- medisyne-items, kankerbehandeling, farmako-ekonomie, koste van kanker. Kanker is die omvattende term wat gebruik word om meer as 100 siektes, wat enige deel van die liggaam kan aantas, te beskryf. Kanker is die onbeheerbare verdeling van abnormale selle in die menslike liggaam, wat nabygelee weefsel kan binnedring en deur die bloedstroom kan versprei na ander dele van die liggaam (National Cancer Institute, 2007b). Kanker kan enige persoon affekteer, ongeag die ras, samelewingsgroep of ouderdom van die persoon (Albrecht, 2006:3). Die behandeling van kanker word al hoe duurder as gevolg van nuwe en meer effektiewe middels wat die mark betree (Niezen et al., 2006:2887) en die diagnosering en die vroee opsporing van kanker wat groot vordering toon (Meropol & Schulman, 2007:180). Die algemene doelstelling van hierdie studie was om die medisinale voorskrifpatrone van antineoplastiese en immunomodulerende agente in 'n deel van die privaat- gesondheidssorgsektor te ondersoek. Hierdie navorsing kan as retrospektief en kwantitaltief geklassifiseer word. Data is verkry vanaf 'n medisyne-eis databasis, van 'n farmaseutiese voordeel-bestuursmaatskappy. Die studiepopulasie het uit al die voorskrifte wat een of meer kankermedikasie-item bevat het, bestaan, vir die studie- periode wat strek vanaf Januarie 2005 tot Desember 2006. Verskillende aspekte van kanker is ondersoek om die internasionale en nasionale voorkoms van kanker en kankerbehandeling te bepaal. 'n Oorsig van aspekte van bestuurde-gesondheidsorg is gedoen en deur hierdie studie het dit duidelik geblyk dat farmako-ekonomiese studies en ander bestuurde-gesondheidsorg aspekte 'n groot rol kan speel as inligtingssisteem in die behandelingsbesluite van kanker­ behandeling. Opsommin.q Die voorskrifpatrone van antineoplastiese en immunomodulerende agente is bespreek, geanaliseer en ge'fnterpreteer. Daar is vasgestel dat die hoeveelheid kankerpasiente, die hoeveelheid voorskrifte wat een of meer kankermedisyne-item bevat en die hoeveelheid kankermedisyne-items wat voorgeskryf is, onderskeidelik minder as 1% van die totale hoveelheid pasiente, voorskrifte en medisyne-items op die totale databasis omvat het. In teenstelling daarmee het die totale koste van kankermedisyne-items 4.00% (2005) en 5.31% (2006) van die totale koste van al die medisyne-items op die totale databasis beloop. Dit dui op die relatiewe hoe koste van kankermedisyne-items. In 2005 en 2006 was ongeveer 50% van alle kanker pasiente op die medisyne-eis databasis oor die ouderdom van 59 jaar en die totale koste van kankermedisyne- items wat deur pasiente ouer as 59 jaar geeis is, het ongeveer 60% van die totale koste van alle kankermedisyne-items in beide studiejare beslaan. Kankermedisyne- items wat geeis is deur pasiente <19 jaar, het slegs 2% van alle kankermedisyne- items, wat in onderskeidelik 2005 en 2006 geeis is, en minder as 1% van die totale koste van kankermedisyne-items in beide studiejare beslaan.
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    (19) TZZ _T (11) EP 2 569 287 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 413/04 (2006.01) C07D 239/46 (2006.01) 09.07.2014 Bulletin 2014/28 (86) International application number: (21) Application number: 11731562.2 PCT/US2011/036245 (22) Date of filing: 12.05.2011 (87) International publication number: WO 2011/143425 (17.11.2011 Gazette 2011/46) (54) COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE VERBINDUNGEN ALS HEMMER DER ATR-KINASE COMPOSÉS UTILISABLES EN TANT QU’INHIBITEURS DE LA KINASE ATR (84) Designated Contracting States: • VIRANI, Aniza, Nizarali AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Abingdon GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Oxfordshire OX144RY (GB) PL PT RO RS SE SI SK SM TR • REAPER, Philip, Michael Abingdon (30) Priority: 12.05.2010 US 333869 P Oxfordshire OX144RY (GB) (43) Date of publication of application: (74) Representative: Coles, Andrea Birgit et al 20.03.2013 Bulletin 2013/12 Kilburn & Strode LLP 20 Red Lion Street (73) Proprietor: Vertex Pharmaceuticals Inc. London WC1R 4PJ (GB) Boston, MA 02210 (US) (56) References cited: (72) Inventors: WO-A1-2010/054398 WO-A1-2010/071837 • CHARRIER, Jean-Damien Abingdon • C. A. HALL-JACKSON: "ATR is a caffeine- Oxfordshire OX144RY (GB) sensitive, DNA-activated protein kinase with a • DURRANT, Steven, John substrate specificity distinct from DNA-PK", Abingdon ONCOGENE, vol. 18, 1999, pages 6707-6713, Oxfordshire OX144RY (GB) XP002665425, cited in the application • KNEGTEL, Ronald, Marcellus Alphonsus Abingdon Oxfordshire OX144RY (GB) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
  • Preliminary Data from Ongoing Adjuvant Aromatase Inhibitor Trials I

    Preliminary Data from Ongoing Adjuvant Aromatase Inhibitor Trials I

    Vol. 7, 4397s-4401s, December 2001 (Suppl.) Clinical Cancer Research 4397s Preliminary Data from Ongoing Adjuvant Aromatase Inhibitor Trials I Paul E. Goss z Introduction Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada The growth of hormone receptor-positive breast cancer can be altered clinically by several classes of agents that antagonize the effects of estrogen (1). The SERMs, 3 exemplified by tamox- Abstract ifen, constitute one such class of drugs. Pure antiestrogens such With recent results showing letrozole and anastrozole as fulvestrant (Faslodex) also exert a potent antiestrogenic effect to be superior to tamoxifen as initial therapy for advanced and show efficacy in tamoxifen-resistant cell lines in preclinical disease, the aromatase inhibitors are poised to establish their models. Thus, unlike tamoxifen, which exerts both an agonist place in the adjuvant therapy of postmenopausal receptor- and an antagonist effect, fulvestrant is a pure antagonist and acts positive breast cancer. A review of the rationale, design, and by down-regulating ER content (2). preliminary results of the ongoing adjuvant trials that in- Aromatase (estrogen synthetase) inhibitors antagonize the clude aromatase inhibitors will be presented, along with the action of estrogen by reducing its levels both in the circulation ongoing or planned substudies. Two strategies employing and in normal and malignant breast tissue (3). They were ini- aromatase inhibitors after tamoxifen are being evaluated. tially tested in postmenopausal women with breast cancer pro- gression after tamoxifen treatment. A superior outcome with The MA.17 international intergroup trial is randomizing these drugs compared to either megestrol acetate or aminoglu- postmenopausal patients who are disease-free after 5 years tethimide resulted in their becoming the established second-line of adjuvant tamoxifen to an additional 5 years of ietrozole or treatment for ER-positive metastatic breast cancer (4-13).
  • Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R

    Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R

    Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R. SIMPSON* AND MITCH DOWSETT *Prince Henry’s Institute of Medical Research, Monash Medical Centre, Clayton, Victoria 3168, Australia; †Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, United Kingdom ABSTRACT Endocrine adjuvant therapy for breast cancer in recent years has focussed primarily on the use of tamoxifen to inhibit the action of estrogen in the breast. The use of aromatase inhibitors has found much less favor due to poor efficacy and unsustainable side effects. Now, however, the situation is changing rapidly with the introduction of the so-called phase III inhibitors, which display high affinity and specificity towards aromatase. These compounds have been tested in a number of clinical settings and, almost without exception, are proving to be more effective than tamoxifen. They are being approved as first-line therapy for elderly women with advanced disease. In the future, they may well be used not only to treat young, postmenopausal women with early-onset disease but also in the chemoprevention setting. However, since these compounds inhibit the catalytic activity of aromatase, in principle, they will inhibit estrogen biosynthesis in every tissue location of aromatase, leading to fears of bone loss and possibly loss of cognitive function in these younger women. The concept of tissue-specific inhibition of aromatase expression is made possible by the fact that, in postmenopausal women when the ovaries cease to produce estrogen, estrogen functions primarily as a local paracrine and intracrine factor. Furthermore, due to the unique organization of tissue-specific promoters, regulation in each tissue site of expression is controlled by a unique set of regulatory factors.