Chemotherapeutic Prevention Studies of Prostate Cancer (original) (raw)
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Chemoprevention of Prostate Cancer
Hematology-oncology Clinics of North America, 2006
Purpose: Due to the public health impact of prostate cancer including the burden of screening and treatment, there is significant public interest in the potential prevention of this disease. We review the most recent results of large scale randomized clinical trials. Materials and Methods: We review the potential agents, their hypothesized mechanisms of action and challenges for the design of chemoprevention trials, including the 3 large scale trials SELECT (testing selenium and vitamin E), PCPT (testing finasteride) and REDUCE (testing dutasteride). Results: The initial results of SELECT have now been reported and demonstrate no impact of selenium or vitamin E on the risk of prostate cancer. The REDUCE trial results should be available within the year. The results of the PCPT demonstrate a significant (measured relative risk reduction of 24.8%) reduction in the risk of prostate cancer. The initial observation of an excess risk of high grade disease appears to be related to improved detection of cancer and high grade cancer related to the improved sensitivity of prostate specific antigen, digital rectal examination and prostate biopsy for cancer and high grade cancer detection. Modeling studies suggest that with finasteride the risk of high grade cancer is unchanged or reduced. Sexual dysfunction and gynecomastia were observed but the rates were low. Conclusions: Recommendations for the prevention of prostate cancer must be based on outcomes of well designed randomized trials. Men undergoing prostate cancer screening should be informed of the potential for the reduction in risk with finasteride.
A Perspective on Prostate Carcinogenesis and Chemoprevention
In this perspective, modifiable carcinogenic factors for the prostate are summarized. This is followed by a discussion of how current knowledge about causation of prostate cancer and chemoprevention of prostate cancer can be used to develop preventive strategies. Prostate cancer is a slowly developing cancer which offers opportunities for preventive interventions. Only a few randomized clinical trials of prostate cancer prevention have been completed. The SELECT study with selenium and vitamin E did not find protective effects, but in two trials with 5α-reductase inhibitors risk was reduced about 25 %, showing that chemoprevention is possible and indicating that the androgen receptor is a suitable target. Besides smoking cessation and reduction of obesity, there are no known dietary or life style interventions that will have a major impact on prostate cancer risk. Inflammation of the prostate is an attractive target, and aspirin may be a promising candidate agent, but has not been a...
Prostate cancer and the influence of dietary factors and supplements: a systematic review
Nutrition & Metabolism, 2014
Background: Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. Aim: To review the key evidence available for potential chemopreventive nutrients. Methods: The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words "diet and prostate cancer", "nutrition and prostate cancer", "dietary factors and prostate cancer", "prostate cancer epidemiology", "prostate cancer prevention", "prostate cancer progression". Results: Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. Conclusions: From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population.
Integrative Cancer Therapies, 2002
in cooperation with the Southwest Oncology Group has begun one of the largest prostate cancer prevention studies to date, the Selenium and Vitamin E Chemoprevention Trial (SELECT). The purpose of this article is to review the evidence and discuss the individual antioxidant compounds under study. The authors comprehensively reviewed the peer-reviewed literature on the chemoprevention of prostate cancer with emphasis on the antioxidants vitamin E and selenium. The credible leads for the primary prevention of prostate cancer using selenium and vitamin E have emerged as secondary findings from randomized controlled trials with corroborative evidence from observational and in vitro studies. Selenium and vitamin E are widely available compounds that are safe if taken in moderation, with relatively few adverse effects. The evidence in support of the antioxidants in the primary prevention of prostate cancer is promising, and the next step in definitively answering the question has been addressed by the investigators of SELECT. The SELECT study will define the role of the antioxidants selenium and vitamin E in the prevention of prostate cancer; complete data from the study will be available in 12 years.
Journal of Carcinogenesis, 2011
Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1) Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2) chemoprevention drugs including agents interfering with androgen action, and (3) antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.
Anticancer Research, 2019
Background/Aim: Prostate cancer is one of the most common cancers in men which remains a global public health issue. Treatment of prostate cancer is becoming increasingly intensive and aggressive, with a corresponding increase in resistance, toxicity and side effects. This has revived an interest in nontoxic and cost-effective preventive strategies including dietary compounds due to the multiple effects they have been shown to have in various oncogenic signalling pathways, with relatively few significant adverse effects. Materials and Methods: To identify such dietary components and micronutrients and define their prostate cancer-specific actions, we systematically reviewed the current literature for the pertinent mechanisms of action and effects on the modulation of prostate carcinogenesis, along with relevant updates from epidemiological and clinical studies. Results: Evidence from various recent experimental, clinical and epidemiological studies indicates that select dietary micronutrients (i.e., lycopene, epigallocatechin gallate, sulforaphane, indole-3-carbinol, resveratrol, quercetin, curcumin & piperine) and zinc play a key role in prostate cancer prevention and progression and therefore hold great promise for the future overall management of prostate cancer. Conclusion: A formulation that comprises these micronutrients using the optimal, safest form and dosing should be investigated in future prostate cancer chemoprevention studies and as part of standard prostate cancer therapy.
Dietary Agents in the Chemoprevention of Prostate Cancer
Nutrition and Cancer-an International Journal, 2005
Nutritional factors have been estimated to contribute 20-60% of cancers around the globe, and almost one-third of deaths are being reported in Western countries. According to estimates by the American Cancer Society, during the year 2005 about 232,090 new cases of prostate cancer will be diagnosed alone in the United States and 30,350 men will die of this disease. The high incidence and long latency period of prostate cancer offer plenty of time to pursue strategies toward prevention and/or treatment to suppress or revert this disease. Epidemiological evidence suggests that plant-based dietary agents decrease the risk of some types of human cancer, including prostate cancer. Intake of 400-600 g/day of fruits and vegetables is associated with reduced risk of several cancers. The use of micronutrients and/or other phenolic agents in the diet or synthetic exogenous supplements to prevent neoplastic transformation of normal cells or to slow the progression of established malignant changes in cancer cells is termed "chemoprevention." Considerable attention has been devoted to identify plant-based dietary agents that may serve as natural inhibitors of prostate carcinogenesis. Much progress has been made in the last decade in this area of investigation through identification of pathways that play important roles in prostate tumorigenesis. This article summarizes epidemiological, clinical, and mechanistic studies and the significance of plant-derived dietary agents such as flavonoids, indoles, isothiocyanates, phenolics, monoterpenes, and complementary and alternative agents in the management of prostate cancer with recommendations for future studies to advance this area of research.
Prevention of prostate cancer through custom tailoring of chemopreventive regimen
Chemico-Biological Interactions, 2008
One practical way to control cancer is through chemoprevention, which refers to the administration of synthetic or naturally occurring agents to block, reverse or delay the process of carcinogenesis. For a variety of reasons, the most important of which is human acceptance, for chemopreventive intervention naturally occurring diet-based agents are preferred over synthetic agents. For a long time, the prevailing mantra of cancer chemoprevention has been: "Find effective agents with acceptable or no toxicity and use them in preventing cancer in relatively healthy people or individuals at high risk for developing cancer". In pursuing this goal many naturally occurring phytochemicals capable of affording protection against carcinogenesis in preclinical settings in experimental animals have been described. However, clinical trials of single agents have yielded disappointing results. Since carcinogenesis is a multistage phenomenon in which many normal cellular pathways become aberrant, it is unlikely that one agent could prove effective in preventing cancer. This review underscores the need to build an armamentarium of naturally occurring chemopreventive substances that could prevent or slow down the development and progression of prostate cancer. Thus, the new effective approach for cancer prevention "building a customized mechanism-based chemoprevention cocktail of naturally occurring substances" is advocated.