Phase III prostate cancer prevention trials: Are the costs justified?

University of Texas at San Antonio, San Antonio, Texas, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2005; 23(32):8161-4. DOI: 10.1200/JCO.2005.02.7987
Source: PubMed


One randomized, prospective clinical trial for chemoprevention of prostate cancer has been completed, and two additional trials are ongoing. The investment, time, and effort for these trials are substantial. We reviewed the outcomes of these trials to address the value of the investment. The outcomes of the Prostate Cancer Prevention Trial (testing finasteride) and the design of the Selenium and Vitamin E Cancer Prevention Trial (SELECT; testing vitamin E and selenium) trial as well as the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial (testing dutasteride) were reviewed. From a public health standpoint, there is tremendous potential for benefit from large-scale cancer prevention trials. Because of the volume of data that are collected, potential discoveries related to the biology of the disease are substantial. Translational scientific efforts are direct outgrowths of these studies. Prospective, randomized chemoprevention trials for prostate and other cancers are expensive and require long periods of time to conduct, yet the rewards are on a par with the investment.

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    • "The rationale for this study was based partly upon early results from the NPC study. Exhaustive attempts were made to recruit large numbers of American men, including ethnic minorities (Cook et al., 2005; Lippman et al., 2005), involving extensive publicity and considerable expense (Thompson et al., 2005). However, the trial was controversially stopped partway through its’ planned course, because of safety concerns (Lippman et al., 2009; Mueller et al., 2009; Schrauzer, 2009). "
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    ABSTRACT: Selenium (Se) is an important micronutrient that, as a component of selenoproteins, influences oxidative and inflammatory processes. Its' levels vary considerably, with different ethnic and geographic population groups showing varied conditions, ranging from frank Se deficiencies to toxic effects. An optimum Se level is essential for the maintenance of homeostasis, and this optimum may vary according to life stage, general state of health, and genotype. Nutrigenetic studies of different Se levels, in the presence of genetic variants in selenoproteins, suggest that an effective dietary Se intake for one individual may be very different from that for others. However, we are just starting to learn the significance of various genes in selenoprotein pathways, functional variants in these, and how to combine such data from genes into pathways, alongside dietary intake or serum levels of Se. Advances in systems biology, genetics, and genomics technologies, including genetic/genomic, epigenetic/epigenomic, transcriptomic, proteomic, and metabolomic information, start to make it feasible to assess a comprehensive spectrum of the biological activity of Se. Such nutrigenomic approaches may prove very sensitive biomarkers of optimal Se status at the individual or population level. The premature cessation of a major human Se intervention trial has led to considerable controversy as to the value of Se supplementation at the population level. New websites provide convenient links to current information on methodologies available for nutrigenetics and nutrigenomics. These new technologies will increasingly become an essential tool in optimizing the level of Se and other micronutrients for optimal health, in individuals and in population groups. However, definitive proof of such effects will require very large collaborative studies, international agreement on study design, and innovative approaches to data analysis.
    Frontiers in Genetics 04/2011; 2:15. DOI:10.3389/fgene.2011.00015
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    • "To date, much of what is known about diet and PC comes from epidemiologic investigations that are limited in their ability to show cause and effect, in vitro studies or interventions in animal models which may or may not have relevance to the disease course in humans, or small clinical pilot studies that lack adequate control or that rely on indirect endpoints of disease (e.g., prostate specific antigen [PSA])[2]. Hence, we look to large-scale randomized controlled trials (RCT), such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT) [3], to provide us with convincing evidence that dietary factors do indeed make a difference; however, these trials are both time- and resource-intensive [4,5]. The presurgical model has been proposed as an efficient means of assessing the impact of various interventions on PC [6]; this model also can be applied to studies of dietary factors. "
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    ABSTRACT: The time between the diagnosis of cancer and a planned definitive surgical procedure offers a strong and direct approach for assessing the impact of interventions (including lifestyle interventions) on the biology of the target tissue and the tumor. Despite the many strengths of presurgical models, there are practical issues and challenges that arise when using this approach. We recently completed an NIH-funded phase II trial that utilized a presurgical model in testing the comparative effects of flaxseed supplementation and/or dietary fat restriction on the biology and biomarkers associated with prostatic carcinoma. Herein, we report the rationale for our original design, discuss modifications in strategy, and relay experiences in implementing this trial related to the following topics: (1) subject accrual; (2) subject retention; (3) intervention delivery; and (4) retrieval and completion rates regarding the collection of paraffin-embedded and fresh frozen prostate tissue, blood, urine, ejaculate, anthropometric measures and survey data. This trial achieved its accrual target, i.e., a racially-representative (70% white, 30% minority) sample of 161 participants, low rates of attrition (7%); and collection rates that exceeded 90% for almost all biospecimens and survey data. While the experience gained from pilot studies was invaluable in designing this trial, the complexity introduced by the collection of several biospecimens, inclusion of a team of pathologists (to provide validated readings), and shifts in practice patterns related to prostatectomy, made it necessary to revise our protocol; lessons from our experiences are offered within this article. While our experience specifically relates to the implementation of a presurgical model-based trial in prostate cancer aimed at testing flaxseed-supplemented and fat-restricted diets, many of the lessons learned have broad application to trials that utilize a presurgical model or dietary modification within various cancer populations.
    Clinical Trials 02/2008; 5(3):262-72. DOI:10.1177/1740774508091676 · 1.93 Impact Factor
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    • "In conclusion, they found ED to be a forewarning symptom for subsequent diagnosis of cardiovascular disease and suggested that ED should lead clinicians to consider further evaluation for cardiovascular disease [33]. Other studies are in progress that will characterise the impact of finasteride on sexual function and changes in sexual function over time in older men [34]. In addition, as the largest and longest clinical trial using finasteride, PCPT will illuminate the natural history of BPH and shed more light on clinical outcomes such as voiding symptoms and surgical interventions for BPH. "
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    ABSTRACT: Provide a critical summary of the latest interpretation of findings from the Prostate Cancer Prevention Trial (PCPT). Findings from PCPT and recently published post-hoc analyses are reviewed. PCPT demonstrated that finasteride can reduce the prevalence of prostate cancer, permitted the first large-scale assessment of the performance characteristics of prostate-specific antigen for prostate cancer screening, and identified new-onset erectile dysfunction as an early predictor of cardiovascular events. PCPT has and will continue to yield valuable information regarding future strategies for prostate cancer prevention and detection, benign prostatic hyperplasia, and other matters of public health importance.
    European Urology 02/2007; 51(1):27-33. DOI:10.1016/j.eururo.2006.09.002 · 13.94 Impact Factor
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