Prostate Cancer, Nutrition, and Dietary Supplements

Prostate Cancer, Nutrition, and Dietary Supplements

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Although nutrition plays a role in the development of prostate cancer, no specific diet can prevent or eradicate this disease. Prostate cancer, like other cancers, is an extremely complex process. No single factor (eg, diet) can explain the various facets of this disease. Nevertheless, the use of diet and dietary supplements for reducing the risk of developing prostate cancer or for treating prostate cancer continues to engage the interest of patients and researchers. [1]

Before discussing or recommending a dietary or lifestyle pattern that may help prevent prostate cancer or inhibit its progression, it would seem prudent to touch on probability, which should inform discussions of the role of nutrition in the prevention of any disease. Reviewing the most common causes of morbidity and mortality allows for an easier understanding of dietary changes that should be recommended in general. 

Recommendations should be simple, logical, practical, and at the very least probability-based, similar to any other evidence-based medicine topic. Additionally, with any general dietary and lifestyle recommendations, the maxim “first do no harm” should also apply, given the history of some past recommendations—especially in the area of dietary supplements whose risk was ultimately found to outweigh their benefit.

In the United States, as in virtually every region of the world, cardiovascular disease (CVD) is the number one overall cause of mortality; indeed, CVD has been the leading cause of death in the US every single year since 1919. [2] Cancer is the second leading cause of death in the US and in most developed countries, and is expected to mirror the number of deaths from CVD in the future in various regions of the world. Currently, however, more than 300,000 US men die of CVD every year, [3] whereas fewer than 30,000 die from prostate cancer. [4]

Thus, for the average US man, CVD prevention should take precedence over prostate cancer prevention, based on probability and cumulative research. Fortunately, most of what is known concerning lifestyle and dietary change for CVD prevention appears to directly apply to cancer prevention. [5, 6]

The largest US and worldwide trials of pharmaceutical-based prostate cancer primary prevention exemplify the urgent need for a more proper and balanced perspective. For example, results of the Prostate Cancer Prevention Trial (PCPT) garnered attention plus controversy regarding the use of finasteride daily versus placebo to reduce the risk of prostate cancer. [7, 8, 9, 10] However, the results also provided information that has not received adequate exposure and debate in the medical literature: Of the more than 18,000 men included in this randomized trial, 5 men died from prostate cancer in the finasteride and in the placebo arm, but 1123 men in total died. [7] Thus, prostate cancer was responsible for less than 1% of the deaths; the majority of deaths were from CVD and other non-prostate causes. 

The largest clinical trial ever conducted on the use of dietary supplements to prevent cancer was the selenium and vitamin E supplementation randomized trial (SELECT). [11] It was terminated approximately 7 years early because of a lack of efficacy, and even a potential negative impact with these supplements at the dosages used. Once again, CVD represented the primary cause of mortality overall in this study, with over 500 deaths from this cause compared with a single death from prostate cancer in 5 years of follow-up. In short, every prostate cancer study with survival as the endpoint has found that most patients die of causes other than prostate cancer, mostly CVD.

With that in mind, the lifestyle recommendations proffered in this article are intended to serve CVD and prostate health simultaneously.  Lifestyle or dietary changes that can potentially impact all-cause morbidity and mortality rather than just disease-specific morbidity and mortality again appear to provide the greatest benefit-to-risk ratio. The principal message from nutritional studies in humans has been an endorsement of the benefits of a diet consisting mainly of vegetables, fruits, fiber, and fish, combined with restricted caloric intake and/or exercise to maintain or achieve a healthy weight.

These measures have been associated with a reduced cancer mortality, although no studies have indicated that they can slow the growth of an existing cancer. [12] However, evidence has shown that these dietary measures are effective in reducing the risk of death from CVD. Therefore, the possible merits of nutritional measures in preventing prostate cancer are compounded by their proven merits with regard to CVD.

Ideally, individuals should adopt this type of diet when they are young. Unfortunately, that has not been happening; even with the widespread publicity about the dangers of an improper diet, rates of obesity and diabetes are increasing. [13]

The diagnosis of prostate cancer can be a trigger for dietary improvement, however. In an interview study from the United Kingdom, Avery et al found that over half of men diagnosed with prostate cancer reported making dietary changes, primarily to promote general or prostate health or to facilitate coping. Interest in dietary advice was high. Men whose treatment choice was active surveillance were especially likely to modify their diet and regard diet as an adjunct therapy. [14]

Interestingly, clinicians dealing with prostate cancer patients are at times understandably questioned by these same patients or their family members about what they can tell their sons about prostate cancer prevention, now that there is a family history of the disease. In such cases, the emphasis on reducing CVD risk to as close to zero as possible is often initially surprising to patients and their families, but when the preventive effect on both CVD and cancer—the so-called 2-for-1 benefit—is explained, it seems likely to increase the chances of compliance within the family.

Prostate cancer has become such a frequently diagnosed condition that much research has been undertaken to understand its etiologic factors and how its onset can be prevented, or at least delayed. Although the primary risk factor for developing prostate cancer is aging, the role of diet and nutrition in the development and progression of this and other cancers has received increasing attention. [15]

Heart-healthy dietary patterns appear to be garnering the most attention for their efficacy in preventing prostate cancer or other cancer. They also appear to have the added benefit of increasing longevity or reducing all-cause mortality. One example is the Mediterranean diet, which consists largely of fruits and vegetables, nuts, grains, olive oil, and chicken and seafood (lean sources of protein). A systematic review and meta-analysis of observational studies of the Mediterranean diet found that the highest adherence to this diet was significantly associated with a lower risk of mortality from prostate cancer (risk ratio 0.96, 95% confidence index 0.92–1.00), as well as several other cancers. [12]

This is not meant to imply that a Mediterranean diet offers the only route to heart-healthy changes. Rather, there are numerous dietary patterns that promote improvement in parameters such as blood pressure, cholesterol and blood glucose levels, and weight/waist size, and arguably could impact prostate cancer incidence. The patient’s personal preferences and likelihood of adherence should help guide the decision of which pattern to follow. This is especially relevant when discussing weight loss and obesity.

Obesity is one of the strongest dietary/lifestyle factors associated with prostate cancer. Numerous studies have shown that obese men have a greater risk of developing more aggressive prostate cancer, experiencing disease recurrence despite surgery or radiation therapy, and dying of prostate cancer. [16] For example, in the Health Professionals Follow-up Study (HPFS), long-term weight gain after a diagnosis of localized prostate cancer was associated with an increased risk of lethal prostate cancer in non-smokers. [17]  

Another issue that needs more attention is the correlation between obesity and prostate size or volume. [18] Since weight gain can increase prostate size, it can also reduce the ability of standard biopsies to detect cancer at an earlier stage. Also, with increasing prostate size comes increased secretion of prostate-specific antigen (PSA) from non-cancerous prostate tissue, thus providing a more potentially confusing picture for the clinician and patient. If preventing weight gain could reduce prostate enlargement in some men, that alone could provide substantial clinical benefits.

Some of the best data to support an ideal weight loss diet also can be derived from cardiovascular medicine research, such as the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) study, which was one of the longest (2-years) randomized trials. [19, 20, 21] The results of this and other studies suggest that the “end justifying the means” philosophy appears to be the most beneficial. In other words, as long as an individual can maintain reduced caloric consumption over the long term and weight loss actually occurs, the cardiovascular benefits appear to be similar regardless of the type of diet or macronutrient distribution involved.

Again, adherence is key. Whether a reduced-calorie, low-fat, higher-fat, moderate-protein, or higher-protein approach is selected should be based on individual preference, knowing that long-term significant weight loss (the end result) substantiates the method chosen (the means).

Per-capita fat consumption is highest in males in North America and Western Europe, and rates of prostate cancer deaths are also highest in these regions. (The typical American male obtains about one third of his daily energy intake from dietary fat.) Conversely, the countries in the Pacific Rim have the lowest fat consumption and the lowest prostate cancer death rates.

Whittemore et al studied the relationship of diet, physical activity, and body size in black, white, and Asian men living in North America and found that the only factor that correlated with prostate cancer was the amount of dietary fat. [22] The same was true in Hawaiian men; the highest prevalence of prostate cancer was in men with the highest intake of saturated fat. [23]

The introduction of Western diets in Japan, where the traditional diet is low in fat, has led to an increased incidence of aggressive prostate cancer. Giovannucci et al reported that men who consumed high levels of fat were more likely not only to develop prostate cancer but also to develop a more aggressive form of the disease. [24]

In an animal study by Wang et al, a low-fat diet decreased the growth of prostate tumor cells. [25] These investigators injected prostate cancer cells from the androgen-sensitive cell line (LNCaP cells) into nude mice. Initially, all of the animals were placed on a diet in which 40% of their caloric intake came from fat. When the tumors were established and measurable, the diet was changed. Tumor growth was markedly inhibited in the animals in which dietary fat contributed no more than 20% of the total caloric intake. There was no significant difference in total ingested calories between the 2 groups.

If higher fat intakes are associated with prostate cancer in older studies, why do more recent and more extensive cohort studies and a meta-analysis [26] show minimal to no correlation at best? Perhaps the reduction in saturated fat and replacement with unsaturated fats has provided protection, as was observed in numerous cardiovascular studies. [27] Perhaps it is the need to adjust for countless variables, such as smoking status, overall caloric intake, age, family history, physical activity levels, alcohol consumption, types of fat (eg, omega-3, omega-6), fruit, vegetable, and fiber consumption, and fat-soluble nutrient intake. Thus, it is possible that in older studies, fat consumption may have been a marker or indicator for unhealthy overall behavior (eg, higher caloric intake, less physical activity, smoking).  

Still, it is intriguing that numerous clinical trials have begun examining the impact of higher fat consumption or a ketogenic diet on prostate cancer progression. It seems plausible that if higher fat intake can lead to heart-healthy parameter changes (eg, reduced blood pressure, cholesterol, blood sugar, weight/waist size, inflammation) then the potential for success should somewhat rival what is observed with other heart-healthy dietary programs.

At the other extreme, many adverse cardiovascular risk factors appear to increase prostate cancer risk and/or aggressiveness.  For example, men with metabolic syndrome have been shown to have a higher incidence of prostate cancer, and potentially more aggressive disease at the time of diagnosis. [28]

Saturated fat constitutes the largest proportion of fat in Western diets and is consumed primarily in animal-derived foods. Although the intake of animal fats and saturated fats correlates with prostate cancer risk, this association is not as strong when adjusted for total energy intake, as noted above.

In addition, a direct cause and effect has not been established. Several mechanisms have been suggested to explain the relationship between saturated fatty acids and prostate cancer. They involve insulinlike growth factor-1 (IGF-1), hormone metabolism, and free-radical damage. A low-fat diet, for example, seems to correlate with lower levels of IGF-1, testosterone, and estradiol levels and higher levels of insulinlike growth factor–binding protein 1 and sex hormone–binding globulin. The POUNDS LOST trial suggests similar changes in some of these metabolic markers with a reduced caloric intake and weight loss. [20]

Omega fatty acids

Much attention has been devoted to the benefits of the omega-3 and the deleterious effects of the omega-6 long-chain unsaturated fatty acids. The marine omega-3 fatty acids are potent antioxidants that have demonstrated a beneficial effect in the development of prostate cancer, in animal and epidemiologic studies. Whether the omega-3 fatty acids themselves or the ratio between omega-3 and omega-6 is important has not been elucidated.

Some nutrient tests, such as these omega-index measurements, are promoted to suggest that a favorable alteration reduces disease risk. In fact, the value of these omega-marker tests in prostate cancer is controversial and needs further study. Some cohort studies suggest reduced risk of aggressive prostate cancer with increasing consumption of omega-3.

Other blood marker data from trials such as the Prostate Cancer Prevention Trial suggest increased risk of prostate cancer with greater omega-3 intake, which was an ancillary observation but still important follow in the future, especially in regard to the impact of supplemental omega-3 and cancer risk. [29, 30] Multiple studies of omega-3 fatty acids and heart health are being conducted, and their results and secondary endpoints should provide more clarity in the area of cancer research.

Although marine sources of omega-3 fatty acids receive a good deal of attention, perhaps because of the popularity of these dietary supplements, healthy plant sources of omega-3 fatty acids exist (eg, nuts, seeds). These also appear to be heart healthy and provide other healthy components such as fiber, which has been associated with a lower risk of prostate cancer in some studies.

Prostate cancer is considered to be one of the cancers influenced by the hormonal environment. Perturbations in the sex steroids seem to play an important role in the genesis of prostate cancer, as they do in breast cancer. A higher body mass index (BMI) has been shown to be associated with lower serum levels of testosterone and sex hormone–binding globulin and with higher levels of estradiol. Serum levels of androstenedione are decreased, but the peripheral conversion of androstenedione to estrone and estradiol is increased.

The increase in BMI and change in hormone status could shift the human body into a pro-inflammatory state, which also could be a cause for concern. In addition, the potentially large reductions in testosterone that can occur with weight gain could provide a partial androgen deprivation akin to the androgen deprivation therapy used for advanced prostate cancer. While in the short term this could reduce the risk of an incident prostate cancer, in the long term it could increase the risk of aggressive disease. [31]

Epidemiologic studies have suggested a correlation between red-meat intake and prostate cancer. Giovannucci et al reported that men with the highest intake of red meat were 2.64 times as likely to develop prostate cancer as men with the lowest intake. [24, 32]

The association between meat consumption and prostate cancer is particularly strong with meats that are cooked at high temperatures and charred, including processed meats such as sausages, bacon, and hot dogs. Longer cooking times, increased temperature, barbecuing, and frying of such meats produce larger amounts of compounds such as heterocyclic amines and N-nitrosamines. For example, the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is found in grilled beef, pork, chicken, lamb, fish, and processed meats. Heterocyclic amines and N-nitrosamines have been added to the list of potential carcinogens by the US Department of Health and Human Services.

In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Cross et al found that neither the total amount of meat ingested nor the type of meat (ie, red, white) consumed was associated with prostate cancer risk. However, ingestion of more than 10 g daily of very–well-done meat increased the likelihood of disease by 1.4 times over no consumption. Moreover, men who were in the highest quintile for PhIP consumption were 1.2 times more likely to develop prostate cancer. [33]

Like fat consumption, meat consumption may simply be a marker of an overall unhealthy lifestyle in some individuals. Consumption of fried food, which has been suggested to increase the risk for prostate cancer, may be a similar marker of risk. [34] Nevertheless, given the documented link between fried food consumption and increased risk of cardiovascular disease, including a recommendation to limit consumption of fried food would seem reasonable advice for a patient seeking to reduce prostate cancer risk.

Meat consumption cannot be construed as an “all or nothing” exercise, however, since the popularity of higher protein and so-called paleo diets has provided another path whereby individuals can lose weight and potentially improve heart health. However, men who currently consume substantial amounts of meat or processed meat and who are gaining weight or are unable to lose weight may find that shifting their diet toward leaner meats or to a plant-based diet could be beneficial.

Total energy consumption may be another important factor in the development of prostate cancer. Excessive caloric intake, regardless of its source, may lead to obesity, which correlates with an increased risk of prostate cancer.

Mukherjee et al demonstrated that in castrated and noncastrated mice, regardless of castration (which alone diminishes cancer growth), all of the groups in which energy intake was restricted developed cancers that were smaller and slower growing, had decreased microvessel density, and had a decreased cell-proliferation index. [35] In this study, cancer cells from the Dunning R3327-H and from LNCaP were transplanted into severe combined immunodeficiency (SCID) mice. Diet was not restricted in one group. A second group was castrated and subdivided into 2 subgroups—one with an energy-intake restriction of 20% and one with a restriction of 40%. Finally, another group was not castrated but had caloric restriction.

On the basis of the results of a transgenic mouse model, Huffman et al concluded that the ability of caloric restriction to inhibit cancer development and progression is partially mediated by changes in energy balance, body mass, and body composition rather than just caloric intake. [36] This implies that the risk of developing prostate cancer depends more on excess caloric retention, which leads to obesity, rather than just excessive caloric consumption.

Although these data are compelling in animal models that can be carefully controlled, whether similar results can be expected in humans is unknown. However, the favorable data from cardiovascular research suggests that using reduced total energy consumption to maintain or achieve a healthy weight would provide significant value.

An intriguing theory suggests a role for insulin in the promotion of cancer. Insulin is an important growth factor, and levels of insulin growth factor and its receptor have been shown to be elevated in persons with prostate cancer. Keeping insulin values low may retard the growth rate of prostate cancer cells; this can be achieved only through diet.

A glycemic index has been developed for persons with diabetes, so that they can take advantage of the small amounts of insulin they may produce. This index ranks carbohydrates in different foods on a scale of 0-100, depending on how much those foods increase blood sugar levels after consumption. The consumption of low-glycemic foods lowers blood sugar levels and decreases insulin production. According to this theory, low levels of insulin growth factor would prevent cancer cells from growing as rapidly.

In the 1920s, Ohsawa popularized the concept of a macrobiotic diet, which comprises foods with a very low glycemic index. This stringent diet consists primarily of whole grains and vegetables. Even most fruits are excluded. In contrast, the diabetic diet restricts only those foods with the highest glycemic index, such as the following:

The renewed focus on the role of insulin in preventing or slowing the progression of prostate cancer and other cancers is exemplified by the interest in using metformin for that purpose. [6, 37, 38] Nevertheless, while the Diabetes Prevention Program trial demonstrated that metformin has the ability to prevent type 2 diabetes, an underappreciated finding of that trial was the profound reduction in diabetes risk produced by lifestyle changes (a low-fat diet with total caloric reduction of 450 calories/day and 150 minutes of exercise/week). In fact, lifestyle changes proved significantly more effective than metformin for diabetes prevention (58% versus 31% reduction). [39] Once again, this illustrates the value of an integrated approach to health promotion and disease prevention.

Klein and colleagues at the Cleveland Clinic have produced a working hypothesis that shows the link between inflammation and prostate cancer. [40] Prostatic inflammation is associated with oxidative stress, which stimulates the production of reactive oxidative species (ROS) and reactive nitrogen species (RNS). These bind to DNA and cause mutations. Oxidative stress derived from endogenous and exogenous sources are associated with DNA damage that occurs with aging and plays a role in carcinogenesis. Polyunsaturated fatty acids induce the production of ROS, resulting in the formation of lipid radicals that can cause DNA damage. Semen can also be oxidative, because of the occasional presence of leukocytes and a substantial amount of polyunsaturated fatty acids.

Several mechanisms that can prevent and repair oxidative damage have been identified. Antioxidant enzymes such as phospholipase A-2 remove altered fatty acids, ROS, and RNS, preventing mutations. This one example of the beneficial effects of dietary antioxidants provides evidence that the consumption of foods that promote the production of ROS and RNS should be limited or avoided.

Vance et al reported that dietary antioxidant intake was inversely associated with levels of thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, in benign prostate tissue in men with incident prostate cancer. Trx 1 levels were positively associated with the Gleason score in these patients. Thus, antioxidant intake may affect the redox status within prostate tissue, which in turn may influence prostate cancer aggressiveness. [41]

In general, risk factors for cardiovascular disease (eg, elevation in weight, blood pressure, and blood cholesterol and glucose levels) involve increased chronic inflammation. Several drugs with established roles in cardiovascular prevention have pleiotropic effects that include anti-inflammatory activity and are being studied for prevention of prostate and other cancers, as well as for adjuvant cancer treatment. Notable examples are statins, aspirin, and metformin (SAM). [6]  

All of the dietary nutrients that may reduce the risk of developing prostate cancer are readily available. Whether substituting or adding dietary supplements is advantageous continues to be investigated. The general consensus is that any nutrient that is contained in food is better than an dietary supplement. In addition, several dietary supplements that are marketed as antioxidents have the potential, if used in excess, to increase the risk and/or progression of prostate cancer. [6, 31, 42, 43] No high-quality study has shown that any supplement can significantly reduce the risk for, or progression of, prostate cancer.

However, quantifying the amount of these nutrients in serum and tissues has been difficult. Therefore, the necessary amount of a given supplement is unknown. Conflicting reports that are confusing to the public and to physicians frequently appear in the media. Differences in study populations, methodology, and interpretation of data complicate the comparison of studies.

The reliability of nutrient testing is also an issue. Countless nutrient or antioxidant tests are offered today to consumers who are concerned about cancer, yet the validity of many of these tests—especially as they relate to cancer and other “hard endpoints”—is unknown. Unanswered questions include the following:

Those and other critical questions should be answered before consumers spend their money on these tests. A few examples can help illustrate the complexity of nutrient testing, which has yet to be fully appreciated. 

For example, use of dietary supplements containing large amounts of biotin (marketed as promoting healthy hair, skin, and nails) may interfere with a variety of laboratory tests that are biotin based. High biotin intake may result in artifactually low results on PSA assays, as well as other cancer marker tests (eg, CA125, CA15-3, CEA, CA19). (False increases in thyroid function test results and vitamin B12 assays have also been reported. [44] )

Given the plethora of tests that may be impacted, patients should be advised to stop taking an individual biotin supplement at least 3 days (and perhaps ideally 1 week) before blood testing. Multivitamins that include biotin are usually not a cause for concern.

Systemic inflammation may result in low values on tests for nutrients such as zinc; selenium; and vitamins B6, C, A, and D. [45] This effect may skew interpretation of research findings because it can suggest that a nutrient deficiency increases the risk for a particular disease when in fact the disease itself is decreasing the measured nutrient level.

Vitamin D blood measurements, in particular, may be reduced not only by inflammation but by obesity, smoking, depression, cancer, and lack of physical activity. [43, 45, 46, 47] This could partly explain the lack of an effect of supplementation in some major clinical trials; that is, the inflammatory state may be creating the appearance of a vitamin D insufficiency or deficiency in individuals with adequate vitamin D intake.

Carotenoids are micronutrient antioxidants that are found in orange or yellow fruits and vegetables and in some dark, leafy vegetables, such as spinach and Brussels sprouts. The most common dietary carotenoids include the following:

Lycopene is one of the predominant carotenoids in plasma and in various tissues, including the prostate. It is found in watermelon, tomato and all tomato-based products, pink grapefruit, apricots, papaya, guava, and persimmons. Carrots contain high levels of carotene but contain little lycopene.

Clinical trials that evaluated the role of beta carotene and the risk of developing prostate cancer have indicated, in general, that the risk of prostate cancer is reduced in men with low serum levels of beta carotene who are treated with supplements. However, those findings were generally not from the trials’ primary endpoints.

Overall, individual beta-carotene supplements have proved disappointing in their ability to reduce cancer risk. In fact, two large phase III clinical trials (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention [ATBC] [48] and the Beta-Carotene and Retinol Efficacy Trial [CARET] [49] ) raised the possibility that beta-carotene supplements may increase the risk of lung cancer in current smokers, and the Age-Related Eye Disease Study 2 (AREDS2) suggested a potential increase in the risk of lung cancer in former smokers. [50]

Note that beta-carotenes from dietary sources have not been associated with an increased risk of lung cancer. Patients concerned about beta-carotene study results can be reassured that the adverse findings apply only to individual dietary supplements. 

A high intake of tomato products (10 or more servings weekly) has been associated with a 35% decreased risk of advanced prostate cancer; this was independent of fruit, vegetable, and olive oil intake. Additional studies have reported that the incident risk of prostate cancer was reduced by 25-80%. Other studies did not find this association, but some of those were conducted in populations in whom lycopene intake may have been too low to make an association. [51]

Studies comparing high and low intake of tomatoes reported a 10-20%, statistically significant reduction in prostate cancer risk in men with high intake. Cooked tomato products had a stronger effect than raw tomato products. [51]

In contrast with those older dietary data, however, current data (from pooled analysis of prospective studies and updated robust epidemiologic studies) suggest that consumption of tomato products, as well as most other fruits and vegetables, has minimal to no effect on prostate cancer risk. [52, 53]   Regardless, the potential for fruits and vegetables to reduce cardiovascular risk and potentially assist with weight loss should be emphasized while more research in the area of cancer prevention is being conducted. Other carotenoids such as lutein, beta-cryptoxanthin, and zeaxanthin need more research.

Broccoli, cauliflower, cabbage, Brussels sprouts, bok choy, and kale have high levels of the anticarcinogenic phytochemicals sulforaphane and indole-3 carbinol. These nutrients induce the production of antioxidant enzymes that can protect cells from oxidative damage. Sulforaphane helps to induce apoptosis in damaged cells. In animal studies, indole-3 carbinol has been shown to exhibit antiproliferative and antimetastatic properties.

Findings from a study by Canene-Adams and coworkers implied that plant-derived nutrients are more beneficial in combination than alone. [54] The investigators studied the antitumor activity in the Dunning prostate-cancer animal model. They fed rats various combinations of tomatoes and broccoli and found that tumor growth was significantly reduced owing to reduced cancer cell proliferation and increased apoptosis.

However, as with beta-carotenes, recent pooled prospective studies have found that consumption of cruciferous vegetables has minimal effect on prostate cancer risk. [55] Again, however, this does not negate the general findings that vegetables are not only heart healthy but are the cornerstone of many potentially successful weight loss dietary plans.

Selenium is an essential, nonmetallic trace element that is widely distributed throughout the body. It is a component of multiple antioxidant enzymes and participates in various functions. Epidemiologic studies indicate that selenium is a potential prostate cancer preventive and decreases the growth rate of prostate cancer cells. Plasma, serum, and tissue levels of selenium are inversely associated with the risk of developing prostate cancer.

Selenium is found in Brazil nuts, walnuts, fish (including canned tuna and shellfish), beef, turkey, chicken, eggs, whole grains, garlic, onions, broccoli, cabbage, and mushrooms. One of the problems in obtaining adequate dietary selenium is that the level of selenium in a given plant depends on the soil in which it is growing. For example, produce from the Imperial Valley in California has a higher selenium content than plants grown elsewhere.

Selenium has several forms, each of which may produce differing biologic effects. The protective activities of selenium compounds are thought to be mediated through a metabolite of selenium called methylselenol. Selenomethionine modulates transcript levels of genes involved in cell-cycle and apoptosis pathways, androgen signaling, signal transduction, and transcriptional regulation. At high concentrations, selenomethionine decreases expression of prostate-specific antigen (PSA). Studies with methylselenic acid have shown that similar biologic pathways are affected, but gene expression has distinct differences.

Animal experiments and epidemiologic evidence suggest that selenium has an anticarcinogenic effect due to its action on apoptotic pathways, inhibition of cell proliferation, and antiangiogenesis. Several studies have reported that high selenium levels confer a 50-65% reduction in the risk of prostate cancer over low selenium levels. The Nutrition Prevention of Cancer (NPC) trial reported that the incidence of prostate cancer in men who received selenium supplements was 50% less than in men who received placebo.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) studied the effects of selenium (in the form of selenomethionine, 200 μg daily) and vitamin E alone and in combination in over 35,000 men, but the study was terminated after an average of 5.5 years (SELECT was planned to include 7-12 years of follow-up) when initial results indicated no significant difference between the supplementation and placebo arms. There was a statistically insignificant trend toward more prostate cancer cases in men taking only vitamin E and more cases of diabetes in men taking only selenium. [56]

In their examination of the disparity between the results of the NPC trial and SELECT, the SELECT investigators noted that the NPC trial participants had deficient levels of selenium, and those with the lowest baseline selenium levels derived the most preventive effect, whereas SELECT participants generally were replete in selenium at baseline.

Additionally, clinical trials of individual selenium supplements in patients at high risk for prostate cancer or with localized prostate cancer have demonstrated no impact on disease progression, and even the possibility of increased risk for disease progression and mortality with high-dose supplementation. [57, 58, 59, 60, 61] This is another reason no individual high-dose antioxidant supplement can currently be promoted for reducing prostate cancer risk. 

Of further interest is that in the SELECT trial, selenium supplementation did not reduce prostate cancer risk in men with baseline low selenium status but selenium supplementation in men already replete with selenium from dietary sources increased their risk for aggressive prostate cancer. [62] Again, these findings support the value of emphasizing dietary sources of selenium over individual supplement use for prostate cancer prevention.

Vitamin E is a mixture of various antioxidant tocopherols that are particularly effective against unsaturated fatty acids and that protect against oxidative cell membrane damage. It also seems to lower testosterone levels. Vitamin E is a lipid-soluble antioxidant found in vegetable oils, nut oils (eg, almond, cottonseed, safflower, sunflower), hazelnuts, sweet potatoes, whole grains, and leafy vegetables. Gamma tocopherol is the most prevalent form of vitamin E in the diet, whereas alpha tocopherol, found in dietary supplements, is the most biologically available form.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study reported a 30-40% decrease in prostate cancer incidence and mortality in men receiving 50 IU of alpha tocopherol daily, compared with placebo. [63] The preventive effect of alpha tocopherol supplementation continued several years post-trial and resulted in lower prostate cancer mortality. [64] The Health Professionals Follow-up Study reported a decreased risk of advanced prostate cancer. In both of these studies, the benefit was identified only in smokers. Studies of gamma tocopherol have shown variable responses.

It should be noted that the risk for some nutrient deficiencies is higher in current smokers than in nonsmokers. This suggests the study of whether improving the status of some primary antioxidant nutrients in smokers would reduce the risk for prostate cancer. Of course, regardless of what such research might determine, the impact of quitting smoking on reduction of all-cause morbidity and mortality should be heavily emphasized over any discussion of potential supplementation. 

The Prostate, Lung, Colorectal, and Ovarian Screening trial (PLCO) studied dietary vitamin E, beta carotene, and vitamin C intake and evaluated prostate cancer risk, but the results did not provide strong evidence for the ingestion of large amounts of antioxidants, either from the diet or from supplements, for the prevention of prostate cancer, although smokers did derive some benefit. This was a questionnaire study, and the doses reported by the participants varied.

The SELECT trial found no protective effect from vitamin E, taken alone or in combination with selenium. Ultimately, SELECT found a significant increase in the risk of prostate cancer in healthy men who took a vitamin E supplement. [56]

To the credit of the SELECT research group, participant follow-up continued (54,464 added person-years), which provided data on outcomes after cessation of dietary supplementation. [65] This follow-up period revealed potential harm from supplement use, and perhaps helped change the perception that dietary supplement use in healthy populations is innocuous.

A significant (P=0.008; hazard ratio [HR]=1.17) increased risk of prostate cancer was found in the vitamin E group, but not in the selenium or combination intervention arm. More concerning was a trend toward increased risk of Gleason 7 or higher disease in the intervention arms compared with the placebo group, although that did not reach statistical significance in any group. The increased risk of prostate cancer with vitamin E began to emerge after only 3 years, and was found to be consistent for low- and high-grade disease types—so conceivably, the risk might have attained statistical significance if the trial had continued for several more years. 

The negative results from SELECT cannot be explained by bias or increased biopsy rates. Rather, they suggest that the dietary supplements themselves are the issue, and the confidence intervals have only continued to narrow with time.

The Physicians’ Health Study II (PHSII), a long-term, randomized, controlled trial involving male physicians, found that neither vitamin E nor vitamin C supplementation reduced the risk of prostate cancer or other cancers. [66] The potential for vitamin E supplements to increase the risk of bleeding events (hemorrhagic stroke, HR=1.74; p=0.04) was also observed in this trial. [67]

The major and most important source of vitamin D is sunlight, but this vitamin is also contained in dairy products, eggs, vitamin D–fortified cereals, and fatty fish such as salmon and tuna. Serum 25-hydroxyvitamin D assays are readily available, and many men test as vitamin-D deficient. As discussed above, however, that assay can be influenced by multiple intrinsic and extrinsic factors (eg, smoking, obesity, inflammation). Consequently, this test should not be widely advocated until further validation with so-called hard clinical endpoints has been accomplished.

Guidelines on vitamin D from the Institute of Medicine (IOM), published in 2011, set the Recommended Dietary Allowance for vitamin D at only 600 IU (800 IU in those age 71 and older), because of the concern for toxicity (eg, hypercalcemia, hypercalciuria, nephrolithiasis) and the lack of impressive data to advocate for higher amounts. [68, 69] Admittedly, the IOM recommendations have not been without controversy. [70]

Vitamin D appears to have some of the same historical embellishment issues that occurred before randomized trials of other dietary supplements for prostate cancer, when some clinicians and patients believed that “the more the better”. In fact, results of studies of vitamin D for prostate cancer prevention have not been consistently impressive, and several studies have found no impact or potential harm at higher blood levels. [71, 72, 73]

Vitamin D is important for bone health, but recommendations for higher intakes to support prostate health have not been supported by strong clinical trial evidence. Vitamin D tends to mimic the function of a hormone, which is why caution should be followed because the potential for a U-shaped risk curve (similar to that seen with other hormones, and even alcohol) does exist for men’s health. 

It may be tempting to endorse the general findings of an increased risk of prostate cancer mortality with lower vitamin D blood status, but again the issues with the assay and the history of prostate cancer supplements being discredited argue for a “first do no harm” approach until larger trials are published that give further insight. Clinical trials such as  the VITamin D and OmegA-3 TriaL (VITAL) [74] should be published soon and they will provide further insight into the benefits and limitations of vitamin D supplementation to prevent cancer.

Soy is a rich source of the isoflavones genistein, daidzein, and equol, which have been shown to affect cell-growth pathways and angiogenesis. Isoflavones have also been shown to affect the production and metabolism of androgen and estrogens, which play an important role in the development and progression of prostate cancer.

The traditional Western diet includes minimal amounts of soy, and as a result, few epidemiologic studies that provide useful recommendations have been performed. In animal studies, isoflavones have been shown to have a beneficial effect in the prevention and reduction in the growth rate of prostate cancer.

Still, not enough data have accumulated to recommend soy products for prostate cancer prevention. However, soy can be a part of a protein-based or plant-based diet to reduce the risk of cardiovascular disease.

Polyphenols are found in varying amounts in most fruits and vegetables, as well as in green tea and red wine. These agents act via antioxidant, antiproliferative, and antiangiogenesis pathways and have proapoptotic effects.

Some of the more popular polyphenols have been the catechins in green tea, which have been shown to inhibit cancer cell growth in animal and epidemiologic studies. Epigallocatechin (EGCG), which is a principal ingredient in green tea leaves, interferes with biochemical reactions associated with cellular proliferation and enhances apoptosis. EGCG is a potent inhibitor of the carcinogenic heterocyclic amines (PhIP), which are produced from overcooked or charred meat. [75, 76, 77]

Some preliminary epidemiologic data support increasing green tea and/or EGCG consumption to reduce the risk of prostate cancer. [78] In addition, some preliminary research also suggests that coffee consumption may help to prevent prostate cancer or aggressive prostate cancer. [79] Still, the question remains whether these low-caloric beverages have tangible anti-cancer properties or are just markers of overall healthy behaviors that could cumulatively be responsible for a lower prostate cancer risk. This will be difficult to answer any time soon, but consuming low-caloric beverages to help maintain or achieve a healthy weight is a reasonable recommendation.

Initial observational data on pomegranate juice or extracts suggested a benefit for prostate cancer prevention. Placebo-controlled trials have not demonstrated a consistent impact on prostate cancer, however, and pomegranate juice can contain larger amounts of calories than beverages such as green tea. Thus, the use of pomegranate for prostate cancer prevention cannot currently be supported. [80, 81, 82]

Higher milk intake has been shown to be associated with an increased risk of developing advanced prostate cancer. Whether this is related to the high fat or even caloric content in milk or to the amount of calcium, or possibly to increased serum levels of insulin-like growth factor-I (IGF-I), has not been clarified. [83, 84]

Giovannucci et al hypothesized that the high calcium intake could lower 1,25(OH)2 vitamin-D levels, which would promote increased dedifferentiation of the cancer cells. [85] Their examination of the records of 47,750 men who were participating in the Health Professionals Follow-up Study found that dietary or supplemental calcium was independently associated with increased risk. More importantly, calcium intake of greater than 1500 mg daily was associated with lower vitamin D2 levels and a higher risk of developing an aggressive cancer.

Gao et al also provided evidence suggesting that cancer risk is associated with calcium intake, [86] but Severi and colleagues obtained data from the Melbourne Collaborative Cohort Study that did not support this contention. [87] The interpretation of these findings is that calcium is good, but that too much may be harmful.

Consumers and clinicians need to be aware of the increasing fortified and natural sources of calcium in the food supply and ideally should work with a dietician to calculate their average daily intake of dietary calcium from foods and beverages (eg, fish, vegetables, milk alternatives). For example, numerous milk alternatives—such as almond, cashew, hemp, and soy milk—contain 400-500 mg of calcium per 8 ounces.

Randomized trials in the general population (eg, the Women’s Health Initiative trials) have shown that many individuals consume the recommended amounts of dietary calcium (1000-1200 mg/day) and thus have no need for dietary supplementation. [43] In addition, normalizing calcium intake using dietary sources carries no significant or consistent increased risk of stone disease compared with excessive intake of calcium supplements, which has been associated with an increased risk of stone disease, as well as constipation.

Zinc is commonly used as a dietary supplement. Healthy individuals with a balanced diet consume about 11 mg of zinc daily. Zinc is found in meat and nuts and in vegetables such as chickpeas and beans. Many individuals consume large amounts of supplemental zinc because of the possible health benefits that have been promoted by commercial interests.

The findings that zinc levels are decreased in men with prostate cancer and that zinc suppresses prostate cancer cell growth and invasion have led to the hypothesis that zinc may play a protective role. However, the Health Professionals Follow-Up Study showed an increased risk of prostate cancer in men who consumed more than 100 mg daily. [88] High-dose zinc has been shown to promote prostate cancer development. Studies of persons taking large amounts of zinc have also reported adverse effects on the urinary tract.

In a study of the relationship between zinc intake in black men and risk of prostate cancer by Mahmoud et al, prostate cancer patients had lower zinc intake, with a mean of 11 mg/day versus 14 mg/day, but comparison of tertiles of zinc intake showed a non-significant, non-linear increase in prostate cancer. A dose-response meta-analysis of 17 studies by these authors showed a non-linear trend in the relationship between zinc intake and prostate cancer. [89] Thus, there is no compelling reason to supplement with zinc for prostate health; the amount contained in the diet, with or without a multivitamin (usually the recommended daily allowance), is normally sufficient.

 

Ornish et al showed that in men with early, low-grade prostate cancer, lifestyle intervention consisting of a vegan diet supplemented with antioxidants, aerobic exercise, and stress-management techniques can lower prostate-specific antigen (PSA) levels by a modest 0.25 ng/mL (or 4%). [90] However, a reduction in PSA production does not always mean that the cancer cells have become inactive.

One of the most interesting, and possibly underappreciated, observations from the Ornish trial is that dietary changes alone appeared to reduce low-density lipoprotein (LDL) cholesterol levels as much as a low to moderate dose of a statin. Indeed, cardiovascular health could be tantamount to prostate health.

Dietary modifications, coupled with exercise and lifestyle modifications, may affect cancer growth rates. These measures can be used in concert with accepted therapy.

Relying on diet alone to treat prostate cancer is unrealistic, but using diet to improve overall quality and length of life, especially in regard to the leading cause of mortality in men and women, is realistic and should be constantly encouraged and embraced. With dietary supplements and cancer prevention, the current mantras of “first do no harm” and “less is more” appear to make more sense. There appear to be more supporting data for using individual dietary supplements to reduce specific side effects of cancer treatment, such as taking American ginseng to reduce cancer-related fatigue (CRF). [91, 92]

In addition, only one extensive randomized, placebo-controlled trial has studied the cancer-preventive effect of a single daily multivitamin (Centrum Silver) in healthy men. The Physicians’ Health Study II (PHSII), which followed over 14,000 participants for 11.2 years, found an 8% reduction in the risk of cancer with multivitamin use (a primary endpoint). [93]

Although the reduction was statistically significant, some would argue that it is not clinically significant. Nevertheless, PHSII showed no increase in prostate cancer incidence or mortality in the multivitamin arm. In fact, there was a non-significant reduction in those outcomes, especially in men with a baseline history of cancer, and a non-significant reduction in fatal cancers overall. Other secondary benefits were found, such as a small but significant reduction in cataracts. [94]

Multivitamin use also has the ability to reduce subtle deficiencies, as may develop in patients taking medications (eg, metformin, histamine 2 blockers, proton pump inhibitors) that can profoundly reduce levels of important nutrients such as vitamin B12 and magnesium. [95]

However, patients who want to use multivitamins for prostate cancer prevention should be warned that more is not better: in some of the largest epidemiologic studies, taking more than one multivitamin pill per day has been associated with an increased risk of aggressive prostate cancer. [96]

Seeking dietary and lifestyle solutions that promote cardiovascular health is a sound guide to measures that could also potentially reduce the risk of prostate cancer. Prominent among those is exercise. Substantial and compelling data support the ability of regular exercise to help prevent prostate cancer or reduce its progression—and this in the context of reducing all-cause morbidity and mortality. If for no other reason, the mental health improvement observed with exercise should encourage readers to incorporate regular physical activity to potentially reduce stress, anxiety, and depression. 

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Severi G, English DR, Hopper JL, Giles GG. Re: Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst. 2006 Jun 7. 98(11):794-5; author reply 795. [Medline].

Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. 2003 Jul 2. 95 (13):1004-7. [Medline]. [Full Text].

Mahmoud AM, Al-Alem U, Dabbous F, Ali MM, Batai K, Shah E, et al. Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis. PLoS One. 2016 Nov 8. 11 (11):e0165956. [Medline].

Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, Raisin CJ, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005 Sep. 174(3):1065-9; discussion 1069-70. [Medline].

Barton DL, Soori GS, Bauer BA, Sloan JA, Johnson PA, Figueras C, et al. Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA. Support Care Cancer. 2010 Feb. 18 (2):179-87. [Medline]. [Full Text].

Barton DL, Liu H, Dakhil SR, Linquist B, Sloan JA, Nichols CR, et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013 Aug 21. 105 (16):1230-8. [Medline]. [Full Text].

Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, et al. Multivitamins in the prevention of cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2012 Nov 14. 308 (18):1871-80. [Medline]. [Full Text].

Christen WG, Glynn RJ, Manson JE, MacFadyen J, Bubes V, Schvartz M, et al. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. 2014 Feb. 121 (2):525-34. [Medline]. [Full Text].

Damião CP, Rodrigues AO, Pinheiro MF, Cruz RA Filho, Cardoso GP, Taboada GF, et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J. 2016 Nov-Dec. 134 (6):473-479. [Medline]. [Full Text].

Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst. 2007 May 16. 99 (10):754-64. [Medline].

Mark A Moyad, MD, MPH Research Associate, Phil F Director of Complementary and Alternative Medicine, Department of Urology, University of Michigan Medical Center

Disclosure: Received honoraria from Abbott Labs for speaking and teaching; Received consulting fee from Farr Labs for consulting; Received consulting fee from Guthy Renker for consulting; Received royalty from Guthy Renker for other.

Stanley A Brosman, MD Clinical Professor, Department of Urology, University of California, Los Angeles, David Geffen School of Medicine

Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Urological Association, Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, Western Section of the American Urological Association, Association of Clinical Research Professionals, American Society of Clinical Oncology, International Society of Urology, International Society of Urological Pathology

Disclosure: Nothing to disclose.

Edward David Kim, MD, FACS Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, Sexual Medicine Society of North America, Tennessee Medical Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Endo, Avadel.

Gamal Mostafa Ghoniem, MD, FACS Professor of Urology, Chief, Division of Female Urology, Pelvic Reconstructive Surgery, and Voiding Dysfunction, Department of Urology, University of California, Irvine, School of Medicine

Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urogynecologic Society, American Urological Association, International Continence Society, International Urogynaecology Association, and Society of Urodynamics and Female Urology

Disclosure: Astellas Honoraria Speaking and teaching; Coloplasty Consulting fee Board membership; Uroplasty Consulting fee Consulting

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Prostate Cancer, Nutrition, and Dietary Supplements

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Our milestones: Cisplatin – the story of a platinum-selling life-saver

Our milestones: Cisplatin – the story of a platinum-selling life-saver

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Category: Science blog August 26, 2015 Comments are closed

Professor Ken Harrap and the formula for carboplatin

In the latest in Our Milestones series, we go back to the 1970s to look at how Cancer Research UK scientists played a role in a global quest to develop and fine-tune one of the world’s most successful cancer drugs.

Sometimes the greatest medical advances are found in the most unlikely of places.

Fifty years ago, US-based physicist Barnett Rosenberg and microbiologist Loretta Van Camp wanted to find out whether electrical fields affected the growth of bacteria. So they dunked metal electrodes into the bugs’ nutrient broth. The bacteria failed to grow – forming long strands rather than neat little cells.

But, after much excitement, and a lot of head scratching, it turned out that the reason had nothing to do with electricity. Instead, the effect was due to the electrodes they were using, which happened to be made of a metal called platinum.

This raised an intriguing question: if platinum could kill fast-growing bacteria, could it also kill similarly fast-growing cancer cells?

It was those curious minds that would turn this serendipitous discovery into the development of cisplatin – the first platinum-based cancer drug.

And Cancer Research UK’s scientists would play a part in taking platinum-based drugs from lab bench to patient bedside, and refine them into some of the most effective cancer treatments to date.

Professor Tom Connors

While The Beatles and Led Zeppelin were enjoying their platinum-selling record successes, the 1960s weren’t a swinging picture for all. For anyone diagnosed with cancer at this time, it was mentioned in whispered tones, – back then, only one in four people survived ‘The Big C’ past the 10 year mark.

While early trials of combination chemotherapy in childhood leukaemia brought (premature) hopes that the end was in sight, further cures for other types of cancer failed to materialise. The need to develop new and better treatments was ringing loud and clear.

One of the people on the hunt for novel drugs was Sir Alexander Haddow, then Director of London’s Chester Beatty Research Institute (funded by one of the founding charities that merged to form Cancer Research UK). He heard about Rosenberg’s results at a meeting in the USA and immediately knew this was something special.

Rosenberg had discovered a number of platinum-containing chemicals that could kill bacteria and cancer cells, but it wasn’t clear which of these –if any – was the most suitable for use as a drug to treat patients. But Haddow he knew he had the right people and the right instruments in his chemistry department to turn the bug-killing effects of platinum into new therapies for cancer.

Back in London, Haddow put a young and ambitious pharmacologist – Dr Tom Connors – in charge of sifting through this huge number of platinum-based-hopefuls, to find the best candidate to take forward into clinical trials. Connors was the right man for this large-scale job: he took a thorough approach to testing all possible molecular combinations, searching for the best compromise between toxicity and effectiveness.

Eventually they struck it lucky with a compound known as cis-[PtCl2(NH3)2] – or cisplatin, as we now know it – and by 1971 it was ready to go into clinical trials. At the Royal Marsden Hospital, a team led by Dr Eve Wiltshaw gave cisplatin to patients for the first time in the UK.

Despite challenging side effects, Wiltshaw saw promising results in women with ovarian cancer.

Alongside parallel research in the USA, their work showed the astounding activity of cisplatin to treat many types of cancer, and quickly established it as the ‘gold standard’ treatment for a range of tumours.

And so, in 1978, cisplatin was approved by the US Food and Drug Administration for use in cancer patients. This international super-group of researchers had delivered a hit, and the life-saving promise of the drug was music to doctors’ and patients’ ears.

Seven years after cisplatin became widely available, 25-year-old Tim Parkes was getting ready for a Christmas party. He pulled on some tight trousers as part of his fancy dress costume, and was shocked to notice an unusual swelling between his legs.

Tim Parkes and his daughter Maddi

He put it down to an earlier incident with a cricket ball, but went back to the doctor to get it checked out again just in case.

It turned out to be much more than a sporting injury, and Tim found himself on the operating table by Boxing Day.

As a fit young man, with 2-year old daughter Becky keeping him busy, he was shocked to be diagnosed with testicular cancer, which had spread to his lungs and the lymph nodes in his stomach. He remembered visiting his grandmother in hospital back in the 60s, fading away from the dreaded ‘Big C’ with radiotherapy as her only treatment option.

But this was 1985, and cisplatin was now available.

Tim was told: “Hopefully you’ll be okay when you’re on it – it’s relatively new but it looks to be working” .

Without treatment he was only given eight months to live, so he started cisplatin chemotherapy straight away.

Cisplatin treatment in the 1980s was tough. After a few courses, Tim only needed to see the drip coming towards him down the corridor to trigger aggressive and relentless vomiting. But despite feeling terrible while on cisplatin, Tim was encouraged when his first scan revealed the tumours had reduced in size by an astonishing 50 per cent. More chemotherapy and radiotherapy followed, leading ultimately to the sweetest sound for any patient: his doctor told him he was cured.

Over the following 25 years, Tim has played a range of sports, had an extremely successful career taking his business to America and, against all the odds, had a second daughter – Maddi.

He says, “Before I had cancer I was a bit wild and crazy, and in a way I’m lucky. I had a second lease of life, I did a masters degree, and wanted promotions. I really felt like I wanted to do something with my life.”

But the treatment took its toll. The human body isn’t able to defend itself from heavy metals like platinum, leading to toxic effects to kidneys, nerves and hearing. Tim remembers his oncologist warning him: “This is hammering your system so much that when you get to 50 you are going to have to look out for your kidneys.”

Unfortunately, he was right: Tim now only has part of one kidney still functioning, and is likely to face dialysis or a transplant in the future, alongside a cocktail of medicines that he takes daily, from hormone replacement therapy to drugs that support his pancreas and bowel.

It was long-term side-effects such as these that spurred researchers on. Could they to develop even better, kinder platinum drugs, or find ways to offset their downsides?

By the early 80s, as Tim’s story shows, cisplatin was having a huge impact on patient survival – but it was just the beginning. The pressure was on to make a killer follow-up hit.

Firstly, they needed to unpick the instrument and figure out just how it was working. They discovered that cisplatin was impressively able to interact with and bind to DNA – the instruction manual in every cell – triggering cancer cells to commit suicide. Knowing these mechanisms set the scene for improvements to be made.

This task fell to Professor Kenneth Harrap at The Institute of Cancer Research, who remembers a significant moment when a doctor colleague told him: “I don’t know why you think you’re so fantastic; you need to do something about the toxicity of cisplatin. It is destroying my patients.”

And so the journey began to find a modified version of the drug that retained its effectiveness but without the side effects. Kidney damage was the major issue – so Harrap and colleagues, in collaboration with chemists at the Johnson Matthey company, focused switching parts of the drug’s molecular structure around until they found versions with less harmful effects.

Eventually their work led to the development of a second drug – carboplatin – licensed in the UK in 1986 and still widely used today to treat thousands of patients. And other platinum-based drugs, such as oxaliplatin, have followed on its heels.

Cisplatin is still used today Flicker/haukeland via CC-BY 2.0

These drugs are still used in the treatment of a wide range of cancers, including lung, breast, bladder, cervical and ovarian cancers, and are prescribed for up to one in five of all cancer patients. And thankfully today more powerful anti-sickness tablets and other treatments can help control the side effects they may cause.

From his perspective, Tim is eternally grateful that cisplatin was available, despite the side effects.

The drug has revolutionised testicular cancer treatment: the death rate from the disease has fallen by around 80 per cent since the early 1970s and today, with surgery and combination chemotherapy treatment, 98 per cent of men are cured.

As a result of his experience, he’s a huge advocate for cancer research. “It’s incredible to see what’s been done, where we’ve got to, and the determination to beat it,” he says. “Everyone has a part to play; it touches everyone. We will be successful in beating it.”

We agree. And it’s fair to say this suite of drugs have been a platinum hit, thanks to the many scientists and doctors who worked tirelessly over the years to turn those first inklings of effectiveness into lifesaving drugs.

One of the key players in the story deserves particular recognition. Tom Connors dedicated his whole career to cancer research, but in a cruel twist of fate, it was to be the disease that took his life – Tom died from prostate cancer in 2002. But he left an incredible legacy.

For many people at Cancer Research UK, he was an adviser, a supporter and a friend for over 30 years. He played a huge role in honing our process for clinical trials, ensuring that the best drugs are brought to patients in the quickest time.

We have a duty to continue his life-saving work, striving every day towards new milestones.

– Lucy

Connors TA, Jones M, Ross WC, Braddock PD, Khokhar AR, & Tobe ML (1972). New platinum complexes with anti-tumour activity. Chemico-biological interactions, 5 (6), 415-24 PMID: 4652593

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Our milestones: Cisplatin – the story of a platinum-selling life-saver

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Tracking down the BRCA genes (Part 2)

Tracking down the BRCA genes (Part 2)

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Category: Science blog February 29, 2012 Comments are closed

In part one, we told the story of Cancer Research UK’s involvement in the race to identify BRCA1 – the first known breast cancer gene.

Although this was a very important discovery, it wasn’t the end of the story. Along the way, researchers had discovered evidence suggesting that there had to be at least one more gene out there.

Here we look at how our scientists revealed the identity of the second breast cancer gene, BRCA2, and what the discovery of both these genes means for cancer patients and their families.

As we mentioned in part one, although BRCA1’s discovery was incredibly exciting at the time, researchers found that it wasn’t responsible for every case of inherited breast and ovarian cancers.

Research showed that faults in BRCA1 accounted for most families with many cases of both breast and ovarian cancer that set in at an early age, and just under half of all families affected by multiple breast cancer cases. But the gene wasn’t implicated in any families affected by both male and female breast cancer.  The hunt was now on for the next breast cancer gene – “Breast Cancer 2”, or BRCA2.

Professor Mike Stratton led the team that tracked down BRCA2

The main hurdle in the search for this gene was cleared in 1994 by an international team led by Professor Mike Stratton at The Institute of Cancer Research. With funding from The Cancer Research Campaign (Cancer Research UK’s predecessor), the Medical Research Council and others, the researchers analysed DNA from 15 families from around the world affected by early-onset breast cancer that wasn’t related to BRCA1.

Using painstaking genetic techniques, the researchers pinpointed the location of BRCA2 to a region on one end of human chromosome 13 – a region known to contain a number of different genes. As with BRCA1, scientists around the world then raced to pin down which one of these was BRCA2.

Professor Stratton – along with a team that included several other Cancer Research Campaign-funded scientists, was the ultimate winner. They revealed the identity of BRCA2 in a paper published in the journal Nature at the end of 1995.

Using DNA samples from a set of Icelandic families affected by multiple cases of breast cancer, Stratton and his team had narrowed down the possible location of BRCA2 to a relatively small region of DNA within chromosome 13. Next, they figured out which bits of this region were likely to be genes, and set about reading the DNA sequence of these potential genes in members of 46 families affected by breast cancer unrelated to BRCA1.

In particular, the researchers were hunting for mistakes in the DNA sequence that would stop a gene from being ‘read’ by a cell (genes are instructions that tell a cell to make a particular protein).  After poring over thousands of DNA ‘letters’, the researchers spotted ‘stop signals’ in the same gene in three people from different families.

Could this be the elusive BRCA2?

To confirm BRCA2’s identity, the scientists pulled together the full DNA sequence of their prime suspect. Luckily, this task was made easier by the Human Genome Project – an international consortium of researchers sequencing the entire human genome – who had just published a draft version of the DNA sequence from the end of chromosome 13.

The researchers patched together the sequence of the entire gene and compared it to the DNA of people from families affected by breast cancer.  They found mistakes in the gene in members of several different families, including those affected by male breast cancer. But they didn’t see any faults when they looked at DNA from over 500 healthy women.

This was enough evidence to confirm the identity of the mystery gene as BRCA2.

Since the BRCA genes were identified, they have come under intense scientific scrutiny. We now know that around 1 in 1,000 people carry a fault in one of the genes, and that around 2 in every 100 women with breast cancer have a faulty version of either BRCA1 or BRCA2.

Carrying a faulty version of a BRCA gene means a woman has a roughly 80 per cent chance of developing breast cancer in her lifetime – as opposed to around a 12 per cent chance in the general population, roughly one woman in eight –  and more than a fifty-fifty chance of getting ovarian cancer.

In 1995, our funding allowed scientists at The Institute of Cancer Research to show that BRCA1 faults were more common in younger women who develop breast and ovarian cancer. We now know that faulty BRCA2 is also linked to male breast cancer as well as prostate and pancreatic cancers, and in 2008 our scientists revealed how specific faults in BRCA2 can affect how a patient’s cancer responds to treatment.

People with a strong family history of breast and ovarian cancer are now able to have genetic testing to find out whether they carry a faulty version of BRCA1 or BRCA2. If they do, then they may wish to take steps such as regular breast screening, surgery to remove their breasts or ovaries, or preventative drugs to help reduce their chances of getting cancer.

And in 2009, a baby girl was born as a result of an IVF procedure that ensured she would be free of the hereditary BRCA1 fault that had led to her father’s family being haunted by breast cancer for generations.

We also now know that BRCA1 and BRCA2 aren’t the complete story when it comes to breast cancer genes. Although these two genes have the strongest effect on breast cancer risk, researchers have since discovered many more genes that can influence the chances of getting the disease – and our scientists have been at the forefront of this work.

For example, in 2002, Cancer Research UK-funded scientists in Cambridge and at The Institute of Cancer Research led a team that discovered a new breast cancer gene called Chek2.  And in 2003, a different team of Cancer Research UK-funded scientists in the city tracked down EMSY – a gene that proved to be the missing link between BRCA2 faults (which are only found in hereditary cancers) and randomly-occurring (sporadic) breast cancers.

Cancer Research UK scientists are also leading the way in discovering the more subtle variations in our DNA that have a smaller impact on individual cancer risk.  They were part of a groundbreaking 2007 study that found five new gene regions linked to breast cancer, and in 2010 they found five more. And earlier this year, scientists at our Cambridge Research Institute found the first new ‘cancer accelerator’ oncogene in five years, which is also implicated in up to 4,000 cases of breast cancer every year in the UK

This genetic knowledge is starting to work its way into clinical reality. Our researchers are developing sophisticated computer models – such as a programme called BOADICEA – that can help to predict an individual woman’s risk of breast cancer based on her genetic heritage and family history.

And they’re also calculating how genetic information could help to make breast screening more effective by focusing particular attention on women at highest risk of the disease.

Hundreds of detailed lab studies have revealed what BRCA1 and BRCA2 look like, what they do in cells, how they work, and the other genes and molecules they interact with.  We now know that they help cells repair damage to their DNA, helping to protect us from cancer. If either BRCA gene is damaged or faulty, then the cell can’t repair this damage, increasing the chances of cancer developing.

This finding led to the development of exciting new experimental cancer drugs known as PARP inhibitors, which exploit this genetic ‘Achilles’ heel’ in cancer cells lacking BRCA.  Our scientists, and other groups around the world, are now testing PARP inhibitors in clinical trials with promising early results.  We’ll be covering the development of PARP inhibitors in a future High-Impact Science post, so watch this space.

Across the globe, scientists continue to pore over BRCA1 and BRCA2, trying to understand what makes them tick and how we can use this knowledge to beat cancer.

Just in the past year or so Cancer Research UK scientists have discovered how BRCA1 may be linked to so-called ‘triple negative’ breast cancer, unravelled the complex three-dimensional structure of BRCA2 on an atomic scale, and figured out a molecular ‘volume control’ that helps to determine whether a woman carrying a faulty version of BRCA1 will go on to develop breast cancer.

But there are still plenty of mysteries that need to be solved. For example, it’s still not clear exactly why BRCA1 and 2 faults only cause a relatively small range of different types of cancer – breast, ovarian, prostate and pancreatic – when the faulty genes are found in every cell of the body.  And although the results from the PARP inhibitor trials look good so far, the drugs don’t work for everyone.

Discovering the BRCA genes was just the start. Cancers caused by BRCA faults tend to occur in younger people, and are harder to treat. We urgently need to continue to turn the knowledge gained through research into more and better ways to treat people with cancer. Our researchers have made great strides in the past and – with the help of our supporters – we can make even more progress in the future.

Kat

References

Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, & Averill D (1994). Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science (New York, N.Y.), 265 (5181), 2088-90 PMID: 8091231

Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, & Micklem G (1995). Identification of the breast cancer susceptibility gene BRCA2. Nature, 378 (6559), 789-92 PMID: 8524414

We cover the latest cancer research, including that funded by the charity. We also highlight other relevant material, debunk myths and media scares, and provide links to other helpful resources.

Read our terms and conditions.

Text from Cancer Research UK Science blog by Cancer Research UK, is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License.

Tracking down the BRCA genes (Part 2)

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Where did abiraterone come from?

Where did abiraterone come from?

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Category: Science blog September 21, 2011 3 comments

Abiraterone is taken as a daily tablet

As we’ve reported on our news feed this morning, abiraterone – a cancer drug that we helped discover and develop – has been launched in the UK following licensing by the European authorities.

Men with advanced prostate cancer, who were treated with abiraterone along with a steroid as part of a large clinical trial, survived on average for four months longer than men given just the steroid.

The drug, developed at the Institute of Cancer Research and marketed by Janssen-Cilag, is currently only licensed for men whose prostate cancer has become resistant to chemotherapy, and still has yet to be approved by NICE (or its Scottish equivalent, the SMC) for use on the NHS.

If suitable, it may be available for men in England through the Cancer Drugs Fund  – there’s more about this process over on our CancerHelp UK website, where you can also find a detailed Q&A about abiraterone for patients.

We’ve been following abiraterone’s successes on this blog since 2008, when the results of the first major trials began to emerge. But we thought it would be timely to rewind back to the early 1990s, to the beginning of the story, and look at the invention of the chemical that ultimately became abiraterone.

By the 1990s, researchers and doctors had discovered that the key to managing prostate cancer was to shut off its supply of testosterone, the majority of which is made by a man’s testicles.

Over the years, they’d devised several strategies to do this – initially using castration (orchiectomy, or removal of the testicles), and latterly using hormones like stilboestrol or gonadotrophin-releasing hormone. None of these worked for long; a patient’s PSA levels would gradually start to rise again, and the disease would come back. This became called ‘androgen-independent’ or ‘hormone-refractory’ prostate cancer, and back then there was generally nothing more that could be done.

But measuring testosterone levels in these men’s blood during their treatment gave clues as to what was happening. Hormone treatment would cause a large drop in testosterone, but not to zero. Even though testosterone production by the testicles had been ‘turned off’ (so to speak), the small quantities made by other tissues, such as the adrenal glands, were enough to keep the cancer growing.

And so the hunt was on for a new drug that could completely shut off the body’s supply of testosterone.

Enter a team of chemists led by Professor Mike Jarman, working at what is now the Cancer Research UK Centre for Cancer Therapeutics at the Institute of Cancer Research in Surrey.

Jarman’s team had read about research from the early 1980s, involving an antifungal agent called ketoconazole, which was known to inhibit a key early step in the body’s testosterone production line – an enzyme called cytochrome p450 17A1, or CYP17. Theoretically, targeting this enzyme should shut down testosterone production anywhere in the body.

When given to men with advanced prostate cancer, ketoconazole worked reasonably well at shutting down testosterone production and slowing cancer growth. However, it caused serious side effects, didn’t work reliably and – worst of all – the body broke it down so quickly that men had to be treated three times a day or more.

Nevertheless, these small trials showed that targeting CYP17 was a promising idea. So, armed with a detailed understanding of the chemical reactions CYP17 carried out, the team set about trying to make a molecule in the lab that would mimic ketoconazole’s pros, but with none of its associated cons.

The structure of abiraterone

In the mid-nineties, the team published the fruits of their labours. In a paper in 1995, in the Journal of Medicinal Chemistry, they set out details of how they’d made a whole series of compounds, using intricate and carefully controlled reactions.

All of these compounds, to some degree, blocked the key reactions carried out by CYP17. In fact, as they wrote in the paper,

“The most inhibitory compounds in the present study were far more potent than any inhibitor of [CYP17] for which comparable data have previously been described”

Several of these compounds were extremely promising – they didn’t interfere with other key hormonal processes, and two of them could completely shut off testosterone production in mice. The most promising of them all was described in the paper simply as “3”:

“The evidence…provided here… makes 3 a strong candidate for further development as a potential candidate for the treatment of prostatic carcinoma in humans”

3 would eventually be developed into abiraterone acetate, or to give it its brand name, Zytiga.

It took sixteen more years of hard slog, and collaborative scientific and clinical research, to prove that abiraterone could treat prostate cancer.

First, the drug had to be ‘formulated’ into a pill that could be taken orally (this was done at our Strathclyde Formulation Unit). Then, it had to be vigorously tested in clinical trials. We helped support the initial phase I and II studies, which took place at the Institute of Cancer Research and the Royal Marsden hospital, before the final, costly phase III trials were carried out with the help of the pharmaceutical industry.

Finally it had to go through the various drug-regulatory processes. It has now been licensed to be sold in Europe – and it’s now reached NICE, who are examining whether and how the drug can be made generally available on the NHS.

We’re hoping that NICE makes a speedy appraisal of abiraterone, and that it can be made available to all men who are suitable for treatment. But that’s not the end of the story.

Abiraterone has only been proven effective in men with advanced disease that has stopped responding to chemotherapy. We don’t yet know if it will have the same effect when given to men with less advanced disease. This question is being answered in another trial (which has now closed) and we’re keenly awaiting the results.

And excitingly, abiraterone could be used to treat diseases other than prostate cancer. For example, we’re currently helping to support a trial looking at whether it can treat certain forms of breast cancer.

The story of abiraterone, from the earliest molecular twinkles in its inventors’ eyes through to a fully licensed pharmaceutical is one that exemplifies all the challenges of discovering new cancer drugs.

And even though the story of abiraterone ‘began’ in the 1990s, it wouldn’t have been possible without a prior understanding of prostate cancer’s intimate relationship with testosterone, or of the way the body makes this hormone.

That’s why we spend around 40 per cent of our research funding on the basic biology of cancer – so we can make more fundamental discoveries like this, and translate them into treatments that will ultimately benefit the people we’re all working for – people with cancer.

Henry

Reference:

Potter GA, Barrie SE, Jarman M, & Rowlands MG (1995). Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. Journal of medicinal chemistry, 38 (13), 2463-71 PMID: 7608911

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Kat Arney
November 7, 2011

Hi Yvonne,
We’re sorry to hear about your husband’s prostate cancer and the pain he is suffering. If you or your husband have any questions about cancer or treatment, please do give our Information Nurses a ring on 0808 800 4040 – they’re available from 9am-5pm Monday to Friday.

At the moment, all the data on abiraterone is from clinical trials involving people men with advanced prostate cancer. On average, the drug increases survival in these patients by around 4 months, but it’s difficult to say exactly what benefit the drug might have on any particular person, and we don’t have access to the data about how long individual patients survived on the trial.

Abiraterone is currently being assessed by National Institute of Health and Clinical Excellence, and according to their website they expect to make a decision by May next year: http://guidance.nice.org.uk/TA/Wave26/4

Best wishes to you both,
Kat

yvonne mulhearn
November 4, 2011

my husband is 51 and has advanced prostate cancer. He has had chemotherapy and is currently undergoing radiotherapy to try to allieviate the horrendous leg pain he suffers from due to the metastases in his spine. He has been waiting for aberaterone to be licensed and hopefully he will commence the medication later this month. We were told that it wasn`t a cure but didnot reolise that the extended life expectancy was only around 4 months longer than if he didnt have the treatment. What is the longest someone has survived due to taking abaretarone and when will it be available on the nhs, Yvonne Mulhearn

COLLEEN BROAD
November 4, 2011

GREAT NEWS – WISH IT HAD BEEN ABOUT 10 YEARS AGO!!!!!!!!!

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Category: Science blog February 9, 2011 1 comment

Prostate cancer – the answer’s in the genes

Many of us know someone who’s been affected by prostate cancer – the disease is the most common cancer in men in the UK. Thanks to the efforts of doctors and scientists, more than three quarters of men diagnosed with prostate cancer now survive beyond five years – in the 1970s it was less than a third.

But although huge progress has been made, there are still big challenges to be overcome.

Perhaps the biggest of these is finding a way to tell the difference between prostate cancers that are slow growing and are unlikely to cause any problems, and those that are aggressive and need urgent treatment.

New research by our scientists, published this week in Lancet Oncology, is offering a tantalising glimpse of how this could be possible in the future.

You might think it would be sensible to treat all prostate cancers straight away. But the side effects of treatment can be quite serious – most men won’t want to risk incontinence or impotence unless they really do have a dangerous illness.

And we know that some prostate cancers grow so slowly that they won’t cause any problems in a man’s lifetime – so it’s vital to be able to separate these harmless cancers from the life-threatening ones.

Cell cycle progression genes

Professor Jack Cuzick, one of our researchers based at Queen Mary, University of London, has found a way to spot this difference by measuring the genetic ‘signature’ of prostate cancer. The technique measures levels of a number of genes involved in controlling how healthy cells grow, collectively called ‘cell cycle progression genes’. And in fact two of our scientists – Sir Paul Nurse and Sir Tim Hunt – won a Nobel prize for discovering one of these genes back in the 1980s.

Cancer is caused by cells growing out of control, so cell cycle progression genes really are at the heart of the disease. The theory is that by measuring how active these growth genes are, it’s possible to estimate how fast the cancer will grow, and how aggressive it will be.

Recent research has suggested that this type of genetic signature can predict how long patients with other cancers such as breast, brain and lung cancers survive.  So building on this work, Professor Cuzick and his team were keen to find out if it could be used to solve one of the biggest riddles in prostate cancer research.

Testing the new approach

The researchers tested this approach using around 700 tumour samples from two groups of men – some from the UK, others from the US – who had already been diagnosed with prostate cancer. The men were diagnosed at least nine years ago, meaning that the researchers could compare the real outcomes of their disease with the outcome predicted by the genetic test.

The team collaborated with scientists in America to analyse the samples. One group of men had been treated with surgery to remove the prostate. The other group had cancer that hadn’t spread outside the prostate and didn’t need to be treated immediately. This second group had been given the ‘watch and wait’ option, avoiding treatment for cancers that are unlikely to cause a problem. This set-up allowed the researchers to look at two groups of men who had been managed differently by their doctors.

Reading the signature

To read the genetic signature of each tumour, the researchers used samples of tissue that had been taken when the men were diagnosed or treated. They measured the levels of RNA – a messenger molecule produced by genes – to give them an idea of how active the cell cycle progression genes had been in each tumour. In all, their test measured the activity of 31 cell cycle progression genes. These were chosen because they give a good average measure of the many other genes that control cell growth.

For the group of men who had had their prostates removed, the researchers tested if the genetic signature could predict if the men’s cancers had returned. The results were exciting – they found that tumours with higher levels of RNA from the chosen genes were more likely to have come back after surgery, and the signature could also predict if men were likely to have died after the disease returned.

For the ‘watch and wait’ group who hadn’t been immediately treated, the researchers tested whether the genetic signature could predict if the patient had gone on to die from prostate cancer. Again the signature gave good results – higher scores meant the patient was more likely to have died from the disease.

Importantly, the gene signature test worked best when it was combined with other information about the cancer. The researchers gave each tumour a ‘risk score’ based on the stage the cancer was at, the patient’s PSA score (the levels of a protein produced by the prostate in the patient’s blood), and other factors such as the amount of healthy tissue removed around the prostate if the patient was given surgery. Adding the gene signature score gave more accurate predictions, showing that the test was giving valuable extra information about the cancer.

These are really encouraging results – it looks like the gene signature test could help doctors to predict much more accurately which men can safely ‘wait and see’, and which need immediate treatment. The test also helps to identify men whose cancer appears less harmful, but who in fact have a higher risk of dying from their disease.

So what’s the next step?

The test isn’t yet ready to be part of normal diagnosis and treatment for prostate cancer, but the researchers are working towards this goal. And the results need to be repeated in larger numbers of men, with different backgrounds, to find out how widely applicable they are (for example, there’s evidence that men from certain ethnic minorities are more at risk of prostate cancers – whether this affects their genetic signature needs to be pinned down).

And as the researchers point out in their paper, the gene signature doesn’t measure every gene that might help to predict the outcome of the disease. More research could help to improve the test so that its predictions are even more accurate. Other research in this area is also giving intriguing clues to the genes that could predict if the cancer is likely to spread.

Towards personalised medicine

Finally, and even further in the future, researchers would like to know whether  the gene signature could help doctors decide which treatment will work best for each patient. We won’t know the answer until the signature has been tested as part of clinical trials comparing prostate cancer treatments.

This study has brought us one step closer to more personalised treatment for prostate cancer – it’s a great example of how research into the genes at the heart of cancer could help to improve outcomes for patients. Although it’s still early days, we’ll be watching this space.

Nell

Reference:

Cuzick J et al (2011). Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. The Lancet Oncology PMID: 21310658

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peter england
January 5, 2012

I am a prostate cancer patient who has had radiation treatment and cryotherapy. My PSA is slowly rising from 0.3 to 0.6 over a year. I am 70 but otherwise healthy. If it was possible to volunteer as part of follow-up research I would be interested. Prostate patients face uncertainty when they are diagnosed. This research would, for some patients, remove the imminent fear of early death. When is a test likely to be available, based on this research?

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Prostate cancer trial results should mean fewer hospital trips to have radiotherapy

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Category: Science blog June 20, 2016 12 comments

Radiotherapy has long been a cornerstone of cancer treatment. And it’s particularly important in treating prostate cancer – a disease that affects a huge number of men (more than 40,000 new cases are diagnosed each year in the UK).

The treatment men have depends on what stage their disease is diagnosed. For those diagnosed early, when their cancer is contained inside the prostate and hasn’t spread (so-called ‘localised’ cancer), doctors have three options: daily radiotherapy; surgery to remove their prostate; or monitoring the patient for signs of their cancer becoming more aggressive.

In practice, around 16,000 men each year receive radiotherapy, which is extremely effective. But this can sometimes cause side effects too – and they can be serious.

“Prostate cancer and its treatment are the leading cause of disability in cancer survivors,” says Professor David Dearnaley, from The Institute of Cancer Research, London and consultant at the Royal Marsden. “These side effects can include incontinence – both bladder and bowel – and sexual problems like impotence.”

At the moment, for men given radiotherapy, the gold standard is treatment five days a week, over a period of just over seven weeks. But over the years, evidence has emerged that fewer, stronger doses of radiation could be just as effective in treating the disease. If true, this would mean fewer trips to the hospital for men, potentially fewer side effects, as well as savings for the NHS.

So more than a decade ago, with funding from Cancer Research UK, Dearnaley’s team set out to test this approach in what turned out to be the largest clinical trial of its type in history – the CHHiP trial.

The results, published in full today, should change clinical practice. But there’s a catch: to allow all men who need it to benefit, the NHS needs to invest substantially in new radiotherapy machines – something we’re pressing the Government to do.

In 2002 CHHiP began recruiting men with localised prostate cancer, aiming to test how the size and number of radiotherapy doses might affect survival and side effects.

Over a period of nearly a decade, more than 3,000 men joined the trial and were treated with a type of radiotherapy called intensity modulated radiotherapy (IMRT).

Men were randomly split into three groups:

The men had regular check-ups after treatment, both for any sign of their prostate cancer growing again, and for side effects.

Dearnaley unveiled the top-line results of the study last year at a large European conference. And today, the full data have been published in The Lancet Oncology, and is the result of five years of follow-up.

Reducing the number of treatments men need to get the best outcome is a positive step – Professor David Dearnaley© John Angerson 2016. All rights reserved.

As expected, the standard radiotherapy course was very effective at controlling prostate cancer: after five years almost nine in 10 men (88%) were still free from any signs of their cancer growing.

And if radiotherapy was given in fewer, stronger doses, the 60 Gray overall dose (group two) was just as effective at keeping prostate cancer at bay. And the lower dose of 57 Gray (group three) was only marginally less effective, with 86% of patients seeing their disease under control after 5 years.

But what about side effects? As a result of using IMRT, very few men experienced serious bowel or bladder problems – and this was the same in both groups one and two. This was important, as it showed that stronger daily doses didn’t cause an increase in serious side effects. Similarly, sexual problems, while much more common, occurred at much the same rate in both groups.

But men in the third group, who got the lowest overall dose of radiotherapy (who fared slightly worse in terms of disease control), were slightly less likely to have side effects from their treatment. And, as Dearnaley points out, this means a new option for certain men.

“While the lowest dose wasn’t quite as effective at controlling prostate cancer, the reduced side effects might make it a better option, particularly more elderly or frail men,” Dearnaley tells us.

Giving a bigger dose of radiotherapy with each session requires state of the art radiotherapy machines and precise planning – Professor Malcolm Mason

“This was an important trial to carry out,” says Dearnaley, “because reducing the number of treatments men need to get the best outcome is a positive step.”

“For patients, it means fewer visits to hospital. Their treatment is more convenient and finished sooner, allowing them to go back to their normal lives.”

It also has big advantages for the NHS too. Fewer treatments would cost less – 10s of millions of pounds in savings – and free up radiotherapy resources, potentially reducing waiting times and allowing more time for research.

But using these higher doses of radiotherapy also has implications for how hospitals plan treatment, according to Professor Malcolm Mason, Cancer Research UK’s prostate cancer expert.

“Giving a bigger dose of radiotherapy with each session requires state of the art radiotherapy machines and precise planning,” he says.

“And ensuring treatment is accurate, using the most modern techniques, is paramount.”

So while these findings point to great news for patients, there is still more work to be done to ensure that all hospitals can safely offer this approach to their patients.

The short answer is ‘yes’. In fact, most of the hospitals taking part in the study have already changed to the shorter schedule.

It’s crystal clear from this, the largest trial ever for localised prostate cancer, that men should be treated with fewer, stronger doses

– Professor David Dearnaley

And following the publication of these results, the NHS is looking to change the standard of care for all men. NHS England is in the process making this official, which we understand will happen over summer.

And the health services in Scotland, Wales and Northern Ireland should be doing the same.

“It’s crystal clear from this, the largest trial ever for localised prostate cancer, that men should be treated with fewer, stronger doses,” Dearnaley explains.

“There’s no arguing with the results. And crucially, this was the first study to set limits on the amount of radiation to healthy tissue like the bladder and bowel.”

This is important, he says, because it sets the standard for how men across the country should be treated.

It’s now up to the government and the health service to ensure this can happen. And that’s something we’ll be pressing governments and health authorities to do.

“It’s vital that, once proven in clinical trials, patients across the UK get swift access to the latest innovative radiotherapy treatments,” says Emlyn Samuel, Cancer Research UK’s senior policy manager.

“Last year’s cancer strategy for England called for national funding to urgently update and replace outdated radiotherapy equipment, but we are yet to see any commitment from NHS England or the Government on this,”

“They need to rectify this, so that patients can have the best, evidence-based treatments they need.”

The men on the CHHiP trial are still only five years post-treatment, so Dearnaley and the rest of the team will need to keep monitoring the men for another five to 10 years, to find out if the new radiotherapy dosing has any effect on long term survival.

“Another interesting side story from the trial is we’ve been keeping samples of the tumours,” says Dearnaley. “We’ll be looking at the molecular and genetic characteristics of the tumours to find out if there are ways to predict the best course of radiotherapy for each patient.”

And it’s not the end of the story for research into hypofractionation. As radiotherapy becomes ever more precise, doctors will be able to limit damage to nearby organs more, allowing each treatment to deliver a higher dose. “We could one day see men needing just five or six rounds of radiotherapy,” he says.

And Dearnaley predicts that an important next step will be the development of a new technique called Magnetic Resonance Imaging (MRI)-guided radiotherapy.

“This will be so precise, it will allow us to focus treatment on specific areas within the prostate itself. I think in around five years we’ll be well on the way to using this technology.”

It might seem like a small step, and not as headline-grabbing as a new drug, but this trial will improve the lives of a thousands of patients and lead to financial savings for the NHS.

We’re proud to be supporting the vital clinical trials that are setting the standard of care for cancer patients in the UK.

Emma

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James Pattison
August 8, 2016

In your statement above you say doctors have 3 options for prostrate cancer radiotherapy, cutting it out or monitor this is not strictly true ….as I have prostrate cancer and had treatment last year called brachytherapy it’s the best thing I’ve ever had its minute radioactive implants directly into the prostrate cancer area so would you call this the 4th option ?? guys just ask your doctor….Rob

Gus Robertson
August 6, 2016

Very informative

Filippo Reale
August 5, 2016

Brilliant paper thankyou.

graham snowden
August 4, 2016

I was one of the early recievers of this test and was totaly clear for 10 years. i now recieve hormone treatment which is working well.. i was clear of side effects for those 10 years.

Peter Hanks
August 4, 2016

Just finished Radiotherapy and glad that it was only 4 weeks of treatment I cannot say that your comments regarding side effects are particularly true in my case but still struggling 2 weeks later.
Are all men undergoing this higher frequency treatment automatically enrolled into your survey

Geoff Adams
August 4, 2016

Very Good. Very interesting. Bring on MRI guided radiotherapy asap.

Mr Michael Dagley
August 4, 2016

Very interesting and it looks like things are going the right way.

A
June 22, 2016

The link to the research doesn’t work

Philip Drinkwater
June 22, 2016

Should low dose brachytherapy treatment not get mentioned as one of the current options? I had this at the Christie in Manchester 2 years ago. Very effective with minor side effects.
I am now a volunteer with the cruk north west health awareness roadshow.

Paul
June 21, 2016

Good summary! Should be hypofractionation rather than hyperfractionation though

Kathy
June 21, 2016

Was a longer follow-up considered? In terms of long-term radiation side effects, 5 years is not enough.

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Cracking the cancer code – the International Cancer Genome Consortium

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Category: Science blog July 14, 2011 1 comment

We’re living through a revolution in cancer research. New technology is making it possible to find the genetic changes at the heart of cancer faster than ever before, unlocking the knowledge we need to save lives.

Now Cancer Research UK is taking another big step towards beating cancer by taking part in the most ambitious genetic research effort since the Human Genome Project.

Our scientists and others across the globe are working together as part of the International Cancer Genome Consortium (ICGC), building the largest ever map of the genetic faults that drive 50 different types of cancer.

The International Cancer Genome Consortium (click to enlarge)

ICGC will produce vast amounts of genetic information, and this ‘blueprint for cancer’ will fuel the search for better, more personalised treatments for the millions of people worldwide who are diagnosed with the disease every year. But how?

At the heart of every cancer you’ll find its root cause – damaged DNA. DNA is the instruction manual for our cells, and faulty DNA can make cells grow out of control and form a tumour. Luckily for researchers, a faulty instruction manual means that the story of every cancer – its strengths and its weaknesses – is written in the tumour’s DNA.

But until recently doctors haven’t been able to harness the huge potential of this information. Instead they’ve focused on the differences between the many different types of cancer, using one approach to treat breast cancer and another to treat bowel cancer.

Now we know that every cancer has its own unique ‘signature’ of genetic mutations, meaning that two people with the same type of cancer might benefit from very different treatments. The trick is to understand these signatures, and this is where ICGC comes in.

We already know about the genetic changes that are important in some types of cancer, and this knowledge has brought us ‘targeted’ drugs that exploit specific faults in cancer cells.

For example, patients with a form of leukaemia called chronic myeloid leukaemia can now be tested for a specific gene fault, known as Bcr-Abl. If they carry the fault, they should benefit from treatment with the drug imatinib (Glivec) – and new data suggests that CML patients treated with this drug are effectively cured. But imatinib wouldn’t exist unless researchers had found the Bcr-Abl gene fault that it targets.

This ‘personalised’ approach is the future of cancer treatment, alongside tried and tested techniques like chemotherapy, radiotherapy and surgery.

We’re moving ever closer to being able to select a patient’s treatment based on the genetic profile of their cancer. But for this to become a reality we need to know much more about the faults that drive each type of cancer. ICGC aims to understand each of these faults in exquisite detail.

ICGC is focusing not on inherited faults, but on the genetic ‘mistakes’ that build up over a person’s lifetime.  Most cancers are caused by these ‘acquired’ faults, which determine how each tumour behaves – how it grows, spreads, and responds to treatment. Understanding these faults is the key to finding the best way to treat each patient’s cancer.

ICGC will map the genetic faults in 25,000 tumour samples from patients with 50 different types of cancer, including breast, bowel, ovarian, pancreatic and lung cancers. Cancer Research UK is leading the projects investigating prostate and oesophageal cancer.

For each type of cancer under study, the first step is to read the genetic sequences of tumour samples and healthy tissue taken from 500 patients with that cancer type.

Sequencing this much DNA is an ambitious target that has only recently become possible thanks to advances in technology. Today’s genetic sequencing machines are up to 1 million times faster than those used for the Human Genome Project ten years ago, enabling the scientists involved in ICGC to decode entire cancer genomes quickly and relatively cheaply.

The next step is more complicated. Once the DNA sequences have been decoded, researchers will compare the results of all the samples from each cancer type to find the changes they have in common.

Many of these changes are likely to have no effect on tumour growth – they’re just collateral damage caused by cells dividing out of control. The researchers’ real aim is to find the rare ‘driver’ faults that are fuelling the disease. They will compare the gene sequences from tumour samples with the equivalent sequences from the patients’ healthy tissue to help identify these key faults, which could become targets for new cancer treatments in the future.

We’re proud to be leading the ICGC efforts to map the faults in oesophageal cancer, and jointly leading the prostate cancer project with cancer research organisations in Canada (the Ontario Institute of Cancer Research and Prostate Cancer Canada).

Together, prostate and oesophageal cancer are responsible for over 17,000 deaths each year in the UK alone, and we urgently need new approaches to help save more lives.

The major UK centre for the ICGC prostate cancer project is the Institute of Cancer Research in Sutton, where two of the project’s leaders – Ros Eeles and Colin Cooper – are based. Professor Eeles has an unrivalled track record in identifying genetic changes that contribute to the disease, and Professor Cooper and Cambridge-based Professor David Neal are both leading prostate cancer researchers.  Their combined expertise will ensure that this strand of ICGC makes a real difference to our understanding of the disease.

The prostate cancer team already have access to enough samples to begin sequencing immediately. They aim to start producing data by the end of the year,  and if the results are promising  they may begin to identify key genetic faults within 18 months.

ICGC will help to personalise treatment for prostate cancer by shedding light on the biology of the disease, and in the future it should help us to develop tests to predict which men need immediate treatment and which can safely avoid it.

Oesophageal cancer rates are rising fast in the UK, and unfortunately this type of cancer can be very difficult to treat. Our researchers are already investigating new ways to prevent, detect and treat the disease, and through our contribution to ICGC we hope to help save many more lives in the future.

Dr Rebecca Fitzgerald, a Cambridge-based expert in oesophageal cancer, will be leading Cancer Research UK’s efforts as part of ICGC.

Dr Fitzgerald and her team are still collecting tumour and blood samples. This is likely to take several years, but sequencing will start on the first samples as soon as possible. If the results are as hoped, the team can move on to larger-scale sequencing early next year – and with less than one in ten patients surviving oesophageal cancer for more than five years after diagnosis, progress is urgently needed.

At Cancer Research UK we’re hugely excited by ICGC. It holds real promise for a future where personalised treatment is a reality for even more cancer patients. This huge project will uncover the faults that drive cancer, providing vital knowledge in our fight against the disease.

Armed with these new genetic discoveries, our researchers and others around the world will be able to develop more targeted treatments like imatinib, which will hit cancer where it hurts. And the information from ICGC will also give clues for new ways to prevent cancer and diagnose the disease earlier, helping even more people to live longer lives.

This is only the beginning of an exciting journey of discovery, and we’ll keep you updated on our progress over the coming months and years.

Nell Barrie

Stratton, M., Campbell, P., & Futreal, P. (2009). The cancer genome Nature, 458 (7239), 719-724 DOI: 10.1038/nature07943

Stratton, M. (2011). Exploring the Genomes of Cancer Cells: Progress and Promise Science, 331 (6024), 1553-1558 DOI: 10.1126/science.1204040

Gambacorti-Passerini, C. et al (2011). Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib JNCI Journal of the National Cancer Institute, 103 (7), 553-561 DOI: 10.1093/jnci/djr060

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Anthea Martin
July 14, 2011

The oesophageal cancer ICGC project is being funded through the Catalyst Club, a completely new way of supporting Cancer Research UK. To find out more, take a look at the website
http://supportus.cancerresearchuk.org/Campaign-pages/catalystclub/

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‘Once in a career feeling’ as trial shows offering prostate cancer drug earlier improves survival

‘Once in a career feeling’ as trial shows offering prostate cancer drug earlier improves survival

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Category: Science blog June 6, 2017 21 comments

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In 2012, the drug abiraterone (Zytiga) was first made available on the NHS to treat men with advanced prostate cancer that has stopped responding to standard hormone treatment.

Now, a strong case is being made for the drug to be made available to even more men with prostate cancer.

According to results from the Cancer Research UK-funded STAMPEDE clinical trial, offering abiraterone plus prednisolone in combination with standard therapy to men with prostate cancer earlier, before the disease becomes resistant to standard hormone therapy, can help boost survival.

That’s the take home message from new findings presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago in the US.

The results of the trial, also published recently in the New England Journal of Medicine, show that giving this combination to men whose prostate cancer has spread, or has a high risk of doing so, extends their lives.

Experts have said the results could be practice-changing. So what would this mean for men with prostate cancer?

The STAMPEDE trial is many different trials in one. It’s looking at new combinations of treatments for prostate cancer patients to see which, if any, can improve survival.

Results from some parts of the trial have already been reported. And other parts are still open and available for patients to join.

The part of the trial presented today focused on abiraterone, a drug our research played a leading role in discovering and developing. It works by blocking a molecule inside cells, which stops the body from producing the hormone testosterone. This is important for prostate cancer as testosterone can fuel the growth of tumour cells.

The STAMPEDE team wanted to see if combining abiraterone plus the steroid prednisolone with standard hormone therapy – which blocks or lowers the amount of testosterone in the body – reduced the chances of the disease coming back, or improved survival.

Combining the two could therefore be a double whammy – it would stop cancer cells using testosterone as a fuel to grow, and prevent the production of more testosterone.

It’s one of the biggest improvements in overall survival I’ve seen

– Professor Nick James 

Approximately 1,900 men with prostate cancer who were at a high risk of their disease spreading, or who have prostate cancer that has already spread, took part in the trial and were followed for just over 3 years.

Just under half were treated with standard hormone therapy. The others were treated with standard hormone therapy plus abiraterone and prednisolone.

“We know androgen deprivation therapy works well for a lot of men with prostate cancer. But we wanted to see if we could improve things further,” says Professor Nick James, chief investigator of the STAMPEDE trial based at the University of Birmingham.

“That’s why we looked at combining abiraterone with hormone therapy – to see if this drug could give even more men with prostate cancer even more time with their family.”

When comparing the 2 groups, the researchers looked for 2 key results:

What they found was something James describes as ‘the most powerful results’ he’s seen from a prostate cancer clinical trial.

Men who received the combination of abiraterone plus prednisolone and hormone therapy were far less likely to see their disease spread or get worse compared to those who received only hormone therapy.

But that doesn’t necessarily mean that these men were likely to live longer.

That’s why James and his team also looked at whether the combination improved survival. And it did.

They found that there were fewer deaths in the group who received the combined treatment (184 vs 262). And those men who received the combination were far more likely to be alive 3 years after treatment than those receiving hormone therapy only.

“It’s one of the biggest improvements in overall survival I’ve seen in any clinical trial for adult cancers,” says James. “To be part of something like this is a once in a career feeling.”

He’s also keen to point out that not only does this new combination improve survival and reduce the chances of a man’s cancer coming back, it also does so with fewer side effects.

I really hope these results can change clinical practice

– Professor Nick James 

“As well as improving survival this drug combination also reduced severe bone complications, a major problem for prostate cancer patients, by more than 50%,” he says.

Results from another prostate cancer clinical trial, called LATITUDE, also presented at the conference and published in the New England Journal of Medicine alongside the STAMPEDE trial results.

Excitingly, this trial shows that combining abiraterone and standard hormone therapy lowers the risk of death in men whose prostate cancer has already spread at the time of diagnosis.

The combined treatment also more than doubled the time before patients’ disease worsened, again signalling promise for offering abiraterone earlier in these men.

The purpose of clinical trials is to test new drugs and combinations of drugs to see if they’re better than existing treatments.

In the case of this part of the STAMPEDE trial, it’s certainly done the latter.

And for James, it’s something he hopes will change how men with prostate cancer are treated.

“For me, these results mean abiraterone combined with androgen deprivation therapy should be the new standard of care for men with early stage prostate cancer,” he says.

“I really hope these results can change clinical practice and that this drug can now be used to treat more men with prostate cancer, not just those with advanced disease.”

Áine

Fizazi, K. et al. (2017) Abiraterone plus Prednisone in Metastatic Castration-Sensitive Prostate Cancer. The New England Journal of Medicine. DOI: 10.1056/NEJMoa1704174

James, N.D. et al. (2017) Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. The New England Journal of Medicine. DOI: 10.1056/NEJMoa1702900

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Annie Humphrys
November 22, 2017

My husband has beeen on the combined therapy ie Aberaterone & predisolene & monthly hormone injections. The PSA was rising after having had radiotherapy 9 months earlier. my husbands PSA has dropped to 1.5 & despite reducing the dose the PSA is at the moment stable. The drugs have affected his memory (hence reduced dosage) & weight has been increased around the stomach area. tiredness is another factor but all these side effects are coped with. A brilliant drug!!

Aine McCarthy
September 26, 2017

Hi Pauline,

We’re very sorry to hear about your husband. We would advise you and your husband speak to his doctor. They are be best placed to talk through the treatment options available.

You could also speak to our nurses, freephone on 0808 800 4040, Monday to Friday, 9am to 5pm. They won’t be able to provide advice on which treatment(s) would be best for your husband specifically, but they will be able to talk through the different types of treatment available for men with prostate cancer and offer general support and advice.

Best wishes,

Áine, Cancer Research UK

Pauline Stewart
September 25, 2017

My husband had a prostatectomy 2yrs ago ,unfortunately the op didn’t get clear margin. PSA has continued to rise but he has not been offered any other treatment.Would he be a candidate for this treatment.

Marshall Kinnear
August 17, 2017

Are the drugs mentioned in tour report available to NHS doctors in Scotland?

Aine McCarthy
August 14, 2017

Hi Ian,

Recruitment for this part of the STAMPEDE clinical trial is now closed, but there are other parts of the trial looking at different treatments that are still open. If you or someone you know would like to join STAMPEDE, or any other clinical trial, the best thing to do is speak to your doctor. They will be able to help you find out if there are any suitable trials available to you.

Best wishes,

Cancer Research UK

Ian
August 13, 2017

A fascinating report, thank you. Is there any way one can participate in a trial with this treatment?

Elise Tshikaji
August 10, 2017

Hi,i would like to have the informations on research in some fields in nursing,starting date:available now.Elise

Gerry Leach
August 4, 2017

This news is groundbreaking for all whom suffer from this disease and pressure has to be brought to bear on N.I.C.E To make these drugs available to ALL and NOT a Post code lottery excercise.

Aine McCarthy
August 4, 2017

Hi all,

Thanks for your comments. Based on these new results from the STAMPEDE trial, we hope NICE will recommend abiraterone plus the steroid prednisolone combined with standard hormone therapy as a first treatment for men whose prostate cancer has spread or has a high risk of doing so soon.

NICE (in England, Wales and Northern Ireland) and the SMC (in Scotland) set guidelines about what treatments should be available on the NHS. These organisations take into account a range of evidence including clinical trial results, and balance many different factors to make decisions about what treatments will have the best outcomes for patients.

We’re still waiting to hear when they will review their guidelines in light of these new results from the STAMPEDE trial. We continue to engage with NICE and SMC on improving patient access to new evidence-based cancer medicines.

Abiraterone is available now on the NHS as a treatment for men with advanced prostate cancer that has stopped responding to standard hormone treatment (http://scienceblog.cancerresearchuk.org/2012/05/16/abiraterone-now-available-on-the-nhs-except-in-scotland/). Speak to your doctor about whether or not abiraterone could be suitable for you or someone you know with prostate cancer.

Best wishes,
Áine, Cancer Research UK

John Staniforth
August 3, 2017

I have read about some of this before from Stampede Trial ( which I am participating in).

So why aren’t we being given these additiional drug combinations yet?

I do hope that the bodies involved in hopefully fast-tracking the use of such combinations of drugs do not drag their feet – as I am not getting any younger and my PSA keeps inexorably rising.

John Renshaw
August 3, 2017

Sounds very interesting and promising progress on the project and I am bearing this in mind

Cathy
August 3, 2017

My husband was put onto this trial when diagnosed with advanced metastatic prostate cancer in Feb 2013. His PSA dropped and remains under 0.03% since. We are now in August 2017 so for him this treatment has definitely proved a huge success. The research into cancer is producing some excellent results thank God.

A Penny
August 3, 2017

This is fantastic news but will the government fund this on the NHS. If they allow it, will it be another postcode lottery of who gets the treatment. My uncle has been suffering from aggressive prostate cancer for over ten years, they said treatment similar to this could help. But then was put on a different treatment. No reason was given and now it’s basically a waiting game for the inevitable!

Colin Webb
August 3, 2017

All very good, but how many years will it take before common use. I am speaking as someone who has had prostate cancer, had 2 months of radiotherapy and now find my PSA increasing again.

Robert Shovelton
August 3, 2017

I think this is a very exciting discovery

Graham Bushnell-Wye
August 3, 2017

How effective might this approach be for prostate cancer that has spread to lymph nodes but not yet to bones? I’ve had chemotherapy and ongoing hormone treatment but I’m concerned that the cancer will continue to spread despite a low PSA at the moment.

David Pinion
August 3, 2017

Does this do anything to help prostrate cancer ,recently diagnosed and on last dose of chemo,that had spread to my pelvic bone. PSA running now at 0.3 for several months.

Aine McCarthy
June 28, 2017

Hello,
Thanks for the question.

Both the STAMPEDE and the LATITUDE clinical trials looked at adding abiraterone (Zytiga) to standard hormone therapy and a steroid (prednisone or prednisolone). But, they differ in relation to the groups of men they included.

The STAMPEDE trial was looking at combining abiraterone, prednisolone and standard hormone therapy as a treatment for men with prostate cancer that had spread or who were at a high risk of their disease spreading. The results were published in the New England Journal of Medicine (http://www.nejm.org/doi/full/10.1056/NEJMoa1702900?query=featured_home).

The results of the LATITUDE trial were also published in the New England Journal of Medicine (http://www.nejm.org/doi/full/10.1056/NEJMoa1704174?query=featured_home) and looked at the same combination of drugs – abiraterone and standard hormone therapy – but this time with a different steroid prednisone. This study was also different because it looked at men whose prostate cancer had already spread at the time of diagnosis, and who had not yet been given hormone treatment.

It’s a subtle but important difference. You can read more about these trials on our website (http://www.cancerresearchuk.org/about-us/cancer-news/news-report/2017-06-03-giving-prostate-cancer-drug-earlier-extends-lives-of-men-whose-disease-has-spread?_ga=2.41327073.217671705.1498469716-1079042811.1485172819).

Áine

matua (@chaichairobot)
June 22, 2017

i’m not sure if it’s just me, but the study that you said was published in New England Journal of Medicine (http://www.nejm.org/doi/full/10.1056/NEJMoa1704174?query=featured_home) is not the STAMPEDE trial but the LATITUDE trial. The STAMPEDE trial made use of ADT plus abiraterone. The LATITUDE trial is the one that used ADT plus abiraterone and prednisolone.

pallavi
June 16, 2017

yes the results can change clinical practice scientists done a great job
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Pamela Hale
June 8, 2017

Great news about prostate cancer, congratulations to research scientists.It makes all our groups Cruk funding raising worth worthwhile.

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‘Once in a career feeling’ as trial shows offering prostate cancer drug earlier improves survival

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