Evaluation of Luprolide as ADT - Thesis Example

? Evaluation of Luprolide (Lupron) as a First-Line Medical ADT Intervention in the Treatment of Advanced Pro Cancer: A Measure of Outcomes Over 6 Months, One Year, Two Years, Five Years, and Ten Years. Outline Introduction Prostate cancer as a continuing challenge to modern medical science The threat of prostate cancer in the U.S.A Literature Review Development of prostate cancer Risk factors associated with prostate cancer Pathophysiology Survival and proliferation of prostate cancer cells Medical management of prostate cancer Androgen deprivation therapy Androgen deprivation therapy agents Castration-resistant prostate cancer (CRPC). Luteinizing Hormone-Releasing Hormone (LHRH) Agonists/Antagonists Leuprolide (Lupron) Description of the drug Efficacy evidence Gaps in the evidence of ADT approaches to advanced prostate cancer Developing the Research Problem The Research Problem Hypothesis Research Methodology Site of the study Sampling Measures that will be used in the study Data collection Data analysis Ethical Considerations 1. Introduction In spite of all the dramatic advances in the understanding of disease processes, medical science and medical technologies, cancer remains a disease of special focus in present times, because of the challenges that it continues to pose as a life threatening disease. Most of the cancer diseases tend to be chronic, with a strong possibility of causing the death of the individual, yet take years to develop, before presenting any signs and symptoms of the disease. There is limited clarity in how cancer diseases develop and the exact etiology of most cancers is yet to be clearly defined. Treatment of many cancers involves employing repeated interventions and multiple approaches at the different stages of the disease. The treatment strategy in many of the cancer diseases is more of hope at curing the patients and with the more definite aim of managing the disease, so as to extend the period of survival, with better quality of life in terms of comfort alertness, and function. In the United States of America (U.S.A) the disease of cancer continues to remain a major concern in society, as many of the modern diseases show a declining trend, bit in the case of the cancer diseases more people are developing the disease over the few decades (Grenwald, 2002). Prostate cancer is a cancer that affects the male gender only. Widespread use of prostate-specific antigen (PSA) screening is used in U.S.A. to detect prostate cancer, while it is clinically localized, so that the many forms of interventions available for the early stage of prostate cancer may be used in an attempt to cure the patient of the disease. Yet, many patients still present themselves in hospitals demonstrating evidence of progressive, metastatic, or recurrent prostate cancer. Limited effective treatment strategies are possible in advanced prostate cancer, and in many of the cases, the disease progresses to the palliative care stage. In 2008, 28,660 men died in the U.S.A from prostate cancer, making it the most common malignant disease in men. This statistic points to the need for identifying the treatment strategies that provide the best outcomes for advanced prostate cancer in men, so as to improve the outcome for these patients (Phillips & Petrylak, 2010). 2. Literature Review 2.1. Development of Prostrate Cancer Every cancer has been found to be associated or suspected of association with risk factors. In the case of prostate cancer, evidence from studies have shown that the environmental exposures and dietary nutrients, family history, advancement in age and hormonal factors in conjunction act to alter the genetic architecture in the individual, supporting the proliferation of prostate cancer cells. The use of epidemiological data emphasizes the possibility of environmental factors in the development of prostate cancer. For example, Asians as a racial group are less prone to prostate cancer, for which their poor hygiene and diet are believed to be the cause. This can be seen from Asian migrants in the U.S.A in an environment of better hygiene and richer diet are more prone to prostate cancer than Asians in their home environment (Karan, Thrasher & Lubaroff, 2008). Figure – 1 shows the potential risk factors in the development of prostate cancer. Figure – 1 Potential Risk Factors in the Development of Prostate Cancer (Karan, Thrasher & Lubaroff, 2008) In the etiology of prostate cancer androgens play the most important role and there is the strong belief that it is the binding of androgen dihydrotestotesterone with the androgen receptor that triggers prostate growth. It is speculated that polymorphisms within the key androgen genes are likely to contribute to the risk of an individual developing prostate cancer, as it is quite likely that single polymorphisms can lead to the development of complex, late-onset, and chronic disease like prostate cancer. Identification of the genes involved in the development of prostate cancer will assist in the better risk assessment and management of prostate cancer (Singh et al, 2005). Prostate cancer is initiated when the normal semen-secreting prostate gland mutate into cancer cells, which is classified as an adenocarcinoma or glandular cancer. The common region on the prostate gland where the adenocarcinoma develops is in the peripheral zone. To begin with little clumps of cancer cells develop and remain confined to the normal cells of the prostate gland. This condition is known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). PIN is believed to be strongly involved in prostate cancer, though there is no evidence as yet that it is the precursor to the development of prostate cancer. Subsequently, over time the cancer cells proliferate and move into the surrounding prostrate tissue (stroma) and develop into a tumor. When unchecked this tumor can could become even larger and invade the nearby organs, such as the seminal vesicles or the rectum. The tumor cells also have the ability of migration to other parts of the body by using the blood vessels or the lymphatic system. It is this capacity of prostate cancer to invade other parts of the body that makes it a malignant tumor. The term given to this invasion of prostate cancer to other parts of the body is called metastasis. The organs most commonly invaded by prostate cancer are the bones, lymph nodes, rectum, and bladder (Schiller, 2010). Survival and proliferation of prostate cancer (CaP) cells is dependent on the complex interaction between cell surface receptor-mediated signaling and the transcription factor regulation of gene expression. Androgens play a major influencing role in CaP carcinogenesis and its progression. Androgens also play a similar role in regulating gene and signaling networks, which are responsible for the promotion of the cancer cell survival. This is achieved through the binding with the androgen receptor (AR), which is a ligand-responsive transcription factor. Synthesis in the testicles of testosterone is responsible for as much as 90% of the dihydrotestosterone (DHT) that is formed in the prostate. The rest of the DHT is formed through the less potent adrenal androgens. Intracellular testosterone is converted to DHT by 5 alpha-reductase through its binding to and activation of the androgen receptor. Subsequent to this action, it dimerizes and translocates to the nucleus of the cell to interact with the promoter regions of specific genes and regulate transcription. It is this regulation of transcription that is responsible for the androgens being responsible for a major role in the protein synthesis, cell proliferation, survival, and differentiation of the prostate cancer cells. Targeting this pathway through androgen deprivation has remained the main line of treatment in management of prostate cancer (Gleave, Cox & Wang, 2010). Recent studies have uncovered recurrent gene fusions in most of the prostate cancers, which has clinical implications. Prior to this discovery gene fusion and chromosomal rearrangements were primarily associated with the oncogenic mechanism of hematological malignancies and sarcomas. The finding of gene fusions in prostate cancer changes this picture. Prostate cancer gene fusions that have been identified so far are marked by five genomic regulatory elements, fused to members of the Ets family of transcription, that results in the over expression of oncogenic transcription factors. The genomic regulatory elements identified in prostate cancer gene fusions are normally controlled by androgen. These new findings of the Ets family gene fusions in prostate cancer lead to the surmise that these gene fusions point to a distinct class of prostate cancer, which has implications on the diagnosis, prognosis, and treatment strategies on this distinct class of prostate cancer (Kumar-Sinha, Tomlins & Chinnaiyan, 2008). 2.2. Medical Management of Prostate Cancer Androgen deprivation therapy (ADT) has remained the main intervention modality in the treatment of prostate cancer. Huggins and Hodges seminal work in the early 1940s laid the ground for the development of ADT. In their seminal work they demonstrated that by depriving the prostate cancer cells of androgens through castration or estrogen treatment it was possible to induce cell death or apoptosis in the prostate cancer cells that led to large scale shrinkage of the prostate tumor and its metastases. Bilateral orchiectomy or surgical castration lowers testosterone levels quickly and was the initial means to achieve the aims of the androgen deprivation treatment strategy. However, surgical castration suffers from the drawback that it is an irreversible process and many patients have very strong reservations in using it, due to the psychological impact of the loss of manhood (Pahuja et al, 2010). Diethylstilbesterol and cyperotone were the first two non-surgical interventions developed for ADT. The drawback s of cardiovascular toxicity and thromboembolic toxicity associated with these medical interventions led to their limited use in the treatment of prostate cancer. The introduction of Luteinizing Hormone-Releasing Hormone (LHRH) agonists’ medical interventions gained ground in the treatment of prostate. Leuprolide and goserlin were the first two LHRH agonists that were introduced leading to the increased use of medical interventions for ADT. The use of medical interventions for ADT as a first line therapy for prostate cancer followed as evidence of similar outcomes as surgical castration were found, without the physical and psychological side effects associated with surgical castration and estrogen therapy and currently these two agents remain the standard therapy in the treatment of advanced prostate cancer (Trachtenberg & Mocharnuk, 2000). A more recent introduction to medical interventions in ADT is Aberilix, which is a modified gonadotropin-releasing hormone antagonist, and so unlike the LHRH agonists is a direct LHRH antagonist. This provides the benefit of lack of the flare up phenomenon associated with LHRH agonists. In comparative randomized studies with leuprolide acetate abarexil was found to reduce PSA at a quicker rate than leuprolide. However, since mature follow ups were not conducted there is no evidence available on the long term outcome benefits in comparative terms for the leuprolide and abarexil (Hellerstedt & Pienta, 2002). Appendix – 1 provides the treatment algorithm for prostate cancer after the initial diagnosis of prostate cancer. The duration of ADT may extend from 4, 6, 28 and 36 months and pertains to the duration of the pharmacologic action of LHRH agonist and not the length of time for which the testosterone level is suppressed. Recovery of serum testosterone subsequent to ADT varies widely, and may extend to over a year or in some cases no recovery is seen. Hence, the actual duration of ADT may extend well over the treatment period and the planned duration. The measurement of ADT should be as a function of serum testosterone recovery and not the duration of the testosterone therapy (Buyyounousski, 2010). Anti-androgens offer an option in the medical treatment of prostate cancer, but its hormonal effect has been found to be inferior to medical castration. Cyproterone acetate (CPA) is one such anti-androgen that has been tested in prostate cancer. It is a steroidal, progestational anti-androgen. It works in prostate cancer by the blocking of the androgen-receptor interaction and can cause a reduction in the serum testosterone through a weak anti-gonadotropic action. While it has been tested as a mono-therapy in the treatment of prostate cancer, it has been found to be more useful as an agent to prevent flare-up during the start of LHRH agonist therapy. CPA is well tolerated by patients, but carries with it the risk of promoting cardiovascular complications (Pahuja et al, 2010). Combination of ADT with radiotherapy has proven to be more effective than mere radiotherapy in prostate cancer. The Radiation Therapy Oncology Group trial RTOG 86-1 has demonstrated that use of ADT in combination with radiotherapy for a short duration of four months can cause a delay of the metastatic disease for a period as long as eight years. The exact mode of action by which this benefit is derived is still not clear. It may be due to the action of ADT to potentiate the local effects of radiotherapy or the action of ADT to remove subclinical micro-metastasis. However, there is a total lack of any understanding of the risk factors associated by the combination of ADT with radio therapy, giving rise to the requirement for studies to establish the safety for patients in the combination of ADT with radio therapy, before it is used extensively as a possible substitute for ADT only medical intervention strategies (Buyyounousski, 2010). ADT is a well established treatment strategy for prostate cancer patients and remains the first line of treatment in prostate cancer. However, there exists the problem of castration-resistant prostate cancer associated with ADT. Resistance to the treatment is the problem associated with ADT, which progresses to castration-resistant prostate cancer (CRPC). In spite of the developments in the treatment of CRPC, the prognosis remains poor, leading to early death in such patients. Several processes are involved in the development of CRPC that facilitate the proliferation of the cancer sells and survival of the cancer cells even after ADT. The mechanisms identified as associated with the development of CRPC consist of a complex interaction between clonal selection, reactivation of the androgen receptor axis in spite of serum testosterone remaining at castrate levels, stress-induced pro-survival genes, cytoprotective chaperone networks, and alternative mitogenic growth factor pathways (Koupparis, et al, 2010). Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg.Pro-Gly-NH2) that the hypothalamus in the brain synthesizes, which can induce the release of gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone (FSH) into the systemic circulation of the human body. LHRH agonists are the most commonly employed pharmacological agents in the treatment of prostate cancer, while LHRH antagonists are used as a treatment option in prostate cancer in men and breast cancer in women (Cheng & Mahato, 2008). LHRH agonists were introduced in the 1980s and brought about a sea change in the management of advanced prostate cancer, going on to become the first line treatment in advanced prostate cancer. Form forms of LHRH agonists are currently in use for ADT, and consist of buserelin, goserelin, leuprorelin, and triptorelin. The LRHH agonists are usually administered as depot injections for a monthly, bimonthly, or tri-monthly basis. They hinder the hypothalamic,-pituitary-gonadal axis in testosterone production. At the start of the treatment LHRH agonists stimulate the pituitary LHRH receptor sites, thereby causing a transient rise in LH and FSH release, and as a result there is rise in testosterone production and serum availability, which is known as the testosterone flare phenomenon associated with the use of LHRH agonists. This phenomenon occurs within two to three days of the treatment initiation, and continues for the duration of one week. Consequently the use of LHRH witnesses a transient growth in the prostrate cancer cells, leading to worsening of pain in the bones, obstruction of the outlet of the urinary bladder, obstructive renal failure, and cardiovascular events. Continued use of LHRJ agonists provide their benefits in prostate cancer treatment, consisting of down regulation of the receptors in the pituitary, inhibition of LH and FSH release, and dramatic reduction in testosterone production. Serum levels of testosterone drop to castration levels within a period of 2-4 weeks from the start of LHRH agonist treatment. Comparative studies have demonstrated that LHRH agonist approach is as efficient as DES or orchiectomy approaches to lower testosterone levels in the management of prostate cancer. LHRH antagonist agents like abarelix are later introductions as options in the treatment of prostate cancer and show similar efficacy as the LHRH agonist agents, without the disadvantage of the testosterone flare up phenomenon (Pahuja et al, 2010). 2.3. Leuprolide (Lupron) Leuprolide constitutes a synthetic nonapeptide analogue of naturally produced gonadotropin releasing hormone (GnRH), which is more potent than the natural hormone. Leuprolide is commonly employed as the first line ADR approach to the management of advanced prostate cancer. Leuprolide is available as Lupron Injection, Lupron Depot, Lupron Depot-3 Month, and Lupron Depot-4 Month. Lupron injections containing leuprolide acetate in aqueous solution is essentially meant for pediatric applications and it is the Depot forms that are used in adult prostate cancer. Lupron Depot 3.75mg and 7.5mg come as prefilled dual chamber syringes. One syringe contains sterile lyophilized microspheres of leuprolide and the other syringe contains the diluent. Combined together they form a suspension and are administered as an intramuscular monthly injection. In a similar manner the Lupron Depot-3 month comes as 11.25 and 22.5 leuprolide depots and the Lupron Depot-4 month is available as 30mg leuprolide depots for administering as intramuscular injections once in three months and four months respectively. The effective dosage of Lupron in prostate cancer is 1mg daily subcutaneously or 7.5mg intramuscularly monthly, 11.25mg tri-monthly or 30mg every four months. In advanced prostate cancer the recommended dosage is Lupron 22.5mg administered once in three months (Ho & Gibaldi, 2003). Lupron is among the several GnRH agonist agents that are approved for the palliative treatment of advanced prostate cancer. However, recent concerns on cardiovascular events and diabetes associated with the use of GnRH agonists has caused the FDA to provide guidelines for the use of GnRH agonists that include evaluation of the risks and benefits before using GnRH agonists, and when used monitoring of cardiovascular and diabetes status of the patients (Nelson, 2010). 2.4. Gaps in the Evidence for ADT Approaches to Advanced Prostate Cancer Castration through bilateral orchiectomy or medical castration has remained the traditional frontline approaches for prostate cancer. Formerly the threshold; level of serum testosterone was 50ng/ml, which in recent times has been reduced to 20ng/ml for a more aggressive approach to prostate cancer. A full range of therapeutic agents are available for medical castration, to overcome the reluctance of male patients to undergo surgical castration. These therapy agents consist of diethylstilbesterol estrogen agonists, LHRH agonists, LHRH antagonists, and ketoconozole. (Patterson, Balducci & Pow-Sang, 2002). The Gleason histological score is the primary measure use for prostate cancer tumor aggressiveness, but lacks true prognostic predictive ability. A more reliable measure to identify true prognostic factors is needed in the management of prostate cancer. A recent approach to improve the measure of tumor aggressiveness incorporates PSA levels, Gleason histological score, and tumor volume to discern between low, intermediate, and high-risk tumors, so as to be clearer in identifying management approaches to prostate cancer. Three factors need to be considered in the measure used as prognostic value in prostate cancer consisting of patient and provider factors and tumor characteristics, which seldom is the practice now (Agency for Healthcare Research and Quality, 2008). Moving on to the gaps in the existing evidence of treatment options in advanced prostate cancer, and their efficacy with regard to patient outcomes, the Agency for Healthcare Research and Quality, 2008, report identifies the existing of several gaps. There are limited randomized trials that compare the relative effectiveness between the treatment options, and hardly any that have been conducted within the major treatment category options, making it difficult to arrive at evidence-based conclusions on the efficacy of the several treatment options in the management of prostate cancer. Even among the randomized trials that have been conducted a lacuna exists in that many of these trials have not been suitably powered to provide long-term survival outcomes, and most of them are focused on biochemical progression or recurrence as the main outcomes. Some of the randomized trials are old and focus on the aspects of the treatment of prostrate cancer that are hardly relevant to the current practices in the management of prostate cancer, and therefore contribute little as evidence to the body of knowledge in the treatment options of prostate cancer that are currently employed. Other issue with the trials and studies conducted on the treatment options in prostate cancer include wide variations in the reporting and definitions of outcomes; hardly any findings as evidence towards outcomes with regards to major patient and tumor characteristics; and the lack of evaluation on the emerging technologies and novel treatment options in the management of prostate cancer (Agency for Healthcare Research and Quality, 2008). 3. Developing the Research Problem Several areas lacking in the body of knowledge have been identified by the Agency for Healthcare Research and Quality, 2008, report. There are several options currently available in ADT for use in advanced prostate cancer. This raises the question as to the best option in terms of patient outcomes in the selection of first line treatment for patients with advanced prostate cancer. Answering this question requires several studies to be undertaken, as the evaluation requires examination of the outcomes within each treatment option, comparison between the several ADT treatment options, possible combination with adjuvant treatments and the patient outcomes over suitably extended durations. In essence the Agency for Healthcare Research and Quality, 2008, report identifies these areas as the grey areas in the body of knowledge regarding the efficiency of the various ADT options in the treatment of Prostate cancer. The enormity of the task makes it difficult for a single study to provide answers for the gaps in the knowledge on efficiency of the various ADT options in advanced prostate cancer. 4. Research Problem This study proposes a detailed study on Leuprolide (Lupron) to answer the research problem of the relevance of Leuprolide (Lupron) as a first line treatment approach in advanced prostate cancer patients to better the outcomes of patients. Ablation of the action of androgens through medical or surgical means still remains the standard first-line treatment in advanced prostate cancer. LHRH agonists like leuprolide and goserelin are the most commonly used medical means to achieve this ablation of the action of androgens (Stokes & Chan, 2003). Evaluation of the efficiency of leuprolide is justified on the extent of its continued use as a first line medical option in the treatment of advanced prostate cancer. The study aims to remain concentrated on just leuprolide to provide a clear focus on its role as a first line treatment option in advanced prostate cancer. Furthermore, the study attempts to evaluate the long term outcomes of patients with advanced prostate cancer, who have been administered leuprolide as a first line treatment measure. By this exercise the study attempts to provide greater clarity on the long term outcomes using leuprolide as a first line treatment option, a gap in the body of knowledge as pointed out in the Agency for Healthcare Research and Quality, 2008, report. The findings of the study will provide the benefit of providing data on the long term effectiveness of leuprolide for justifying the continued use of leuprolide as a first line treatment in advanced prostate cancer. This data can also be used for comparison purposes with the findings of other studies on the long term outcomes of using other treatment modalities in advanced prostate cancer. 5. Hypothesis The hypothesis of the study is that leuprolide remains a mainstay in the first line treatment of advanced prostate cancer from the long term outcomes for patients. 6. Research Methodology 6.1. Site of the Study The site of the study will be five oncology centers providing prostate cancer treatment, and using leuprolide as the first line treatment in advanced prostate cancer. 6.1. Sampling Twenty patients treated for advanced prostate cancer will be randomly selected from each of the five oncology centers to provide a sample size of 100. The sample size is important to the good design of a study in medical research (Machin & Campbell, 2005, p.35). According to Daly and Bourke, 2000, p.55, there are three causes for bias in sampling, which are non-random sampling, non-response, and selection bias. To avoid bias in the study random sampling will be used in the study. The study design is such that non-response is not expected to be an issue. To avoid selection a clear inclusion and exclusion criteria will be used. The inclusion criteria will consist of advance prostate cancer patients put on leuprolide as the first line treatment in advanced prostate cancer, where treatment was initiated in an earlier time frame of ten years or more. In essence, this means that advance prostate cancer patients put on leuprolide in January 2001 or earlier will be used in the study, while advance prostate cancer patients put on leuprolide after January 2001 will be excluded from the study. 6.2. Measures that will be used in the Study The following measures will be employed in the study: Age Dosage of leuprolide Duration of leuprolide treatment Duration of testosterone flare up and measures used to contain testosterone flare up PSA levels after 3 months, 6 months, one year, two years, five years, and ten years. Tumor size after 3 months, 6 months, one year, two years, five years, and ten years. Medical events after 3 months, 6 months, one year, two years, five years, and ten years. Whether there was development of CRPC and period of occurrence after treatment initiation. Morbidity picture Mortality picture 6.3. Data Collection Patient records of the samples will be the basis of the data collection. Before collection of the data permission will be sought and received from administration bodies of the respective oncology centers and the patients or their family members. Relevant details required for the study consisting of the age of the patient and the measures will be recorded in separate data sheets for each of the samples. The data collected on the data sheets will form the data for the study. 6.4. Data Analysis Data on the data collection sheet will be collated. Suitable statistical computer programs like SPSS will be used for data analysis. Statistical measurements like p-value from a significance test of null hypothesis, Confidence Interval, correlation, and ANOVA will form the basis of providing the findings of the study, and the reliability of the study. 7. Ethical Considerations Informed consent from patients and confidentiality of patient information are two cardinal principles in medical research (Bhandari & Joensson, 2009). The study will strictly follow these principles. The study will seek all necessary from the ethics administration authorities in the concerned oncology centers before initiating the study. Samples will be selected purely on voluntary basis. The selected volunteers or their family members in case of the demise of the patient will be clearly informed of the purpose of the study, the manner in which the patient records will be used in the study, and the implications, if any for the patients from the study. Willingness to be part of the study will be confirmed through written informed consent sheets. Any clarifications required by the volunteers will be provided. Only after this, will random selection of the volunteers be conducted to provide the participants for the study. Data will be collected unobtrusively in the oncology centers on data sheets. The data sheets will be coded to provide confidentiality of patient information. Other steps will also be taken to increase confidentiality of patient. During the tenure of the study the data sheets will be retained in a secure manner to prevent viewing from anyone outside the authorized study research group. Once the study is completed the data sheets will be handed over to the ethics administration authorities of the respective oncology centers used in the study for their safe keeping or destruction, based on the ethics policies of the oncology centers. Annotated Bibliography Agency for Healthcare Research and Quality. (2008). Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer: AHRQ Executive Summary. Retrieved January 11, 2011, from Medscape Education Web Site: http://www.medscape.org/viewarticle/580896 (This report of AHRQ is based on the research conducted by the Southern California/RAND Evidence-based Practice Center under contract to AHRQ). Bhandari, M. & Joensson, A. (2009). Clinical Research for Surgeons. Stuttgart, Germany: Georg Thieme Verlag. Buyyounousski, M. K. (2010). Androgen Deprivation Therapy in High-Risk Prostate Cancer. Oncology, 24(9), Retrieved January 11, 2011, from Web Site: http://www.cancernetwork.com/prostate-cancer/content/article/10165/1646840. (Buyyounousski, MD, MS, is the Director of Clinical Research, Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA. In this article the author reviews the use of ADT in High-Risk Prostate cancer). Cheng, K. & Mahato, R. I. (2008). Biopharmaceutical Challenges: Pulmonary Delivery of Proteins and Peptides. In Bernd Meibohm (Ed.), Pharmacokinetics and Pharmacodynamics of Biotech Drugs: Principles and Case Studies in Drug Development (pp.209-242). Weinham, Germany: Wiley-VCH Verlag Gmbh & Co.(Prof. Bernd Meinbohm is associated with the University of Tennessee, Health Science Center, Department of Pharmaceutical Sciences, College of Pharmacy, Memphis, TN. This article is from a set of articles published on the details of various biotech drugs). Gleave, M. E., Cox, M. E. & Wang, Y. (2010). Cell Biology of Prostate Cancer and Molecular Targets. In William, D. Figg, Cindy, H. Chau & Eric, J. Small (Eds.), Drug Management of Prostate Cancer (pp.1-24). New York: Springer. (The authors are prostate cancer professionals at the Vancouver Prostate Center and Department of Urological Sciences, Canada. In this article the authors describe the cell biology of prostate cancer and the molecular targets for pharmacological interventions, as a part of a set of articles on pharmacological interventions in prostate cancer). Grenwald, H. P. (2002). Who Survives Cancer? Berkeley, CA: University of California Press. (The author Grenwald, H. P. PhD, School of Policy, Planning, and Development, University of Southern California and Clinical Professor, Social and Behavioral Sciences, School of Public Health, University of Washington, with many published works. In this work book, the author presents the different faces of cancer as a fearsome disease in modern times, in spite of the advances in medical science). Hellerstedt, B. A. & Pienta, K. J. (2002). The Current State of Hormonal Therapy for Prostate Cancer. Cancer Journal for Clinicians, Retrieved January 11, 2011, from Web Site: http://caonline.amcancersoc.org/cgi/content/full/52/3/154 (Dr. Hellerstedt is Fellow, Division of Hematology and Oncology, University of Michigan Medical Center, Ann Arbor, MI, while Dr. Pienta is Professor, Internal Medicine and Urology and Director, Urologic Oncology Program, University of Michigan Medical Center, Ann Arbor, MI. The authors evaluate the current use of hormonal therapies in the treatment of prostate cancer). Ho, R. J. Y. & Gibaldi, M. (2003). Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs. Hoboken, New Jersey: John Wiley & Sons, Inc. (Ho MD and Gibaldi MD are associated with the University of Washington School Pharmacy, Department of Pharmaceutics, Seattle, Washington. The information used in this paper has been extracted from their book that describes the various drugs that have been developed from proteins and genes for the treatment of various diseases). Karan, D., Thrasher, J. B. & Lubaroff, D. (2008). Prostate Cancer: Genes, Environment, Immunity and the use of Immunotherapy. Prostate Cancer and Prostatic Diseases, 11(3), 230-236. (The authors are associated with the Department of Urology, University of Kansas Medical Center, Kansas City; Cancer Research Unit, VA Medical Center, Kansas City; and Department of Urology and Microbiology, University of Iowa, Iowa City respectively. In this article the authors investigate the involvement of genes, environment, and immunity in prostate cancer, and the use of immunotherapy in the management of prostate cancer). Koupparis, A., Casey, R., Robinson, M., & Gleave, M. E. (2010). Novel targeted agents on the horizon for castration-resistant prostate cancer. Future Oncology, 6(12), 1883-1895. (The authors are associated with The Vancouver Prostate Centre & Department of Urological Sciences, 2775 Laurel St., Vancouver, BC, Canada. 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Campbell is associated with the Medical Statistics Group, Institute of General Practice and Primary Care, School Health and Related Sciences, University of Sheffield, UK. The information used in this paper is from their book that details the manner in which medical research studies should be designed). Nelson, R. (2010). FDA Safety Review of GnRH Agonists Used to Treat Prostate Cancer. Retrieved January 11, 2011, from Medscape Medical News Web Site: http://www.medscape.com/viewarticle/721203 (Roxanne Nelson is a staff journalist for Medscape Oncology. The FDA concerns on GnRH agonists are found in her report on the FDA announcement regarding this concern). Pahuja, A., Thwaini, A., Nambirajan, T. & Keane, P. F. (2010). Prostate Cancer. In Iqbal S. Shergill, Manit Arya, Philippe Grange, & Anthony, R. Mundy (Eds.). Medical Therapy in Urology (pp.33-48). London: Springer-Verlag. (The authors are associated with the Department of Urology, Belfast City Hospital, Belfast, U.K. They provide a birds-eye view of prostate cancer and the treatments involved). Patterson, S. G., Balducci, L. & Pow-Sang, J. M. (2002). Controversies Surrounding Androgen Deprivation for Prostate Cancer. Cancer Control, 9(4), Retrieved January 11, 2011, from Medscape Today Web Site: http://www.medscape.com/viewarticle/442384 (Patterson, MD and Pow-Sang, MD are associated with the Genito-Urinary Oncology Program, and Balducci, MD is associated with the Senior Adult Oncology Program at the H. Lee Moffit Cancer Center & Research Institute, Tampa, Florida. In this article the authors take a look at the controversies associated with the use of ADT as first line treatment in prostate cancer) Phillips, C. K. & Petrylak, D. P. (2010). Docetaxel. In William, D. Figg, Cindy, H. Chau & Eric, J. Small (Eds.), Drug Management of Prostate Cancer (pp.133-146). New York: Springer. (The authors are oncology professionals at the Division of Medical Oncology, Columbia University Medical Center, New York. In this article the authors investigate the role of Docetaxel in the treatment of castration-resistant prostate cancer, as a part of a set of articles on pharmacological interventions in prostate cancer). Schiller, J. (2010). Prostate Cancer: Using Research from the Internet. U.S.A.: Jon Schiller Software. (Schiller, J. holds a Doctoral degree in nanotechnology and suffered from prostate cancer. He has researched the Internet to provide valuable information on prostate cancer). Singh, A. S., Chau, C. H., Price, D. K. & Figg, W. D. (2005). Mechanisms of Disease: Polymorphisms of Androgen Regulatory Genes in the Development of Prostate Cancer. Nature Clinical Practice Urology, 2(2), 101-107. (The authors are all associated with the National Cancer Institute, Bethesda. In this article the authors investigate polymorphisms of the androgen regulatory genes to provide a better understanding of the mechanisms involved in the development of prostate cancer). Stokes, Z. & Chan, S. (2003). Principles of Cancer Treatment by Hormone Therapy. Surgery, 21(11), 280-283. (Zuzana Stokes is a Specialist Registrar at the City Hospital, Nottingham, and Stephen Chan is a Consultant Oncologist at City Hospital, Information used is fro their article that lays down the rationale for hormone therapy in the treatment of cancer). Trachtenberg, J. & Mocharnuk, R. S. (2000). Critical Issues in Prostate Cancer Treatment. Retrieved January 11, 2011, from Medscape Education Web Site: http://www.medscape.org/viewarticle/416385 (John Trachtenberg MD is Professor of Surgery, University of Toronto, and Director, Prostate Disease, University Health Network, Princess Margaret Hospital, Toronto, Canada, while Robert, S. Mocharnuk MD, is a Clinical Instructor of Hematology, University of Southern California Keck School of Medicine, Los Angeles, California. The authors trace the treatment issues associated with prostate cancer. Appendix – 1 Treatment Algorithm for Prostate Cancer after Initial Diagnosis ( Read More