Journal of Clinical Oncology

We Are What We Eat, Or Are We?

Posted by

0


Not a clinic day goes by without multiple patients asking me what they should eat, both while on treatment for their cancer and during the survivorship period. If you Google diet and cancer, you are informed that there are 207 million results.1 Such an association seems logical; we all grew up hearing the phase “you are what you eat,” a phrase attributed to French politician and gastronome Jean Anthelme Brillat-Savarin, who wrote in 1826, “Dis-moi ce que tu manges, je te dirai ce que tu es [Tell me what you eat and I will tell you what you are].”2 Despite the persistent belief for the past nearly two centuries, there remain limited, consistent data on most dietary factors and many disease, including cancers.

Studies of red meat and processed meat have been a rare example of fairly consistent results showing an association between increased intake and risk of developing colorectal cancer.3,4 In 2007, The World Cancer Fund and American Institute of Cancer Research‘s expert panel reported that there was convincing evidence that red meat and processed meat increased the risk of developing colorectal cancer.5 Their meta-analyses found that consumption of red meat led to a 1.43 (95% CI, 1.05 to 1.94) increased risk of colorectal cancer per times per week consumed and 1.29 (95% CI, 1.04 to 1.60) per 100 g/d. Similarly, consumption of processed meat was associated with a 1.21 (95% CI, 1.04 to 1.42) increased risk per 50 g/d.4 Given these consistent findings, it seems reasonable to test whether consumption of red or processed meat affected patients who already have a diagnosis of colorectal cancer.

In this issue of Journal of Clinical Oncology, McCullough et al6 report on a cohort of 2,315 subjects who developed colorectal cancer while participating in the Cancer Prevention Study-II Nutrition Cohort. They report that the quantity of red and processed red meat consumed before the diagnosis of colorectal cancer was associated with all-cause but not colorectal cancer–associated mortality. Though not statistically significant, the data suggest that this increase was due to cardiovascular-associated mortality. However, the consumption of red and processed meat after diagnosis was not associated with either end point. Curiously, those with the highest consumption of red and processed meat consistently before and after diagnosis did have an increased risk of colorectal cancer–associated mortality. This seemingly highest risk group (high intake before and after diagnosis) did not have a statistically higher risk of overall or cardiovascular-associated mortality.

Several issues are worthy of consideration in interpreting the McCullough study.6 First, why did an exposure that convincingly increases the risk of developing colorectal cancer not affect the natural history of the disease once it developed?7,8 Although the exact mechanism of action for red and processed meat increasing colorectal cancer development is not known, several plausible biologic mechanisms have been proposed. Red and processed meats cooked at high temperatures contain heterocyclic amines, which are carcinogenic. A second mechanism involves endogenous formation in the gastrointestinal tract of N-nitroso compounds from the heme in red meat, many of which are carcinogenic. In addition, nitrites or nitrates added to meat for preservation could increase exogenous exposure to nitrosamines, N-nitroso compounds, and their precursors. All these proposed mechanisms lead to carcinogenic effects on the mucosa of the bowel, leading to mutational effects on those cells and potential for abnormal growth and cancer formation. The risk of recurrence for patients with nonmetastatic colorectal cancer is related to the growth of micrometastatic disease, already spread before detection and treatment of the primary lesion. Thus, local carcinogenic effects will be less significant to colorectal cancer survivors’ outside risk of forming new primary tumors. In contrast, recent studies on diet and colorectal cancer survivorship have demonstrated association with cancer recurrence, specifically as a result of high intakes of Western-pattern diet and glycemic load.9,10 Both exposures are proposed to be associated with disease recurrence by increasing insulin and insulin-like growth factors, which affect cell growth, proliferation, and metastatic potential, thereby influencing the growth of micrometastatic disease in colorectal cancer survivors.11

Another consideration in survivorship studies is what recommendations can be made to the patient at hand. When a patient is diagnosed with cancer, they want recommendations on what they can do now to help their chances of cure and/or survival. If an exposure before diagnosis is associated with an outcome, but not the exposure after diagnosis, there is not necessarily a recommendation that can be made to a patient. However, such data may suggest a factor that influenced the biology of the tumor that developed. Another question is whether more favorable or less favorable biology influenced by the exposure can be affected by what the patient does after diagnosis. One consideration could be whether a worse prognosis tumor as a result of dietary exposure should influence treatment given to the patient (ie, the factor having prognostic and predictive value). Certainly, studies of diet and lifestyle to date are far from being able to lead to such conclusions. However, it is possible such a mechanism might explain the curious finding that colorectal cancer–associated mortality was influenced by high consumption of red and processed meat both before and after diagnosis, but not in either time frame only. Specifically, patients with high consumption of red and processed meat before diagnosis should try to decrease intake after diagnosis because those who maintained high levels had a higher risk of recurrence. Such a conclusion is purely speculative on the basis of the data in this article and would need other cohorts to further clarify.

Finally, the study by McCullough et al suggests that some risk factors for colorectal cancer also increase risk for other diseases, and thus colorectal cancer patients will often have comorbidities that influence survival. Thus, the current study does remind clinicians that, although one cannot influence exposures before diagnosis, management of comorbidities is important in the care of colorectal cancer survivors to improve survival.

In conclusion, studies of host factors and cancer survival require us to consider whether the results can be of utility to our patients. First, if the exposure after diagnosis influences outcomes, one should consider whether the strength of the evidence justifies making recommendations to alter diet or lifestyle, for instance. Although a randomized controlled trial would be ideal to address this question, changing diet and lifestyle behaviors in the number of patients needed to have statistical powers remains a challenge. Because studies of diet and lifestyle in colorectal cancer survivors are all observational to date, one needs to consider potential biases and confounding. Second, it is important to understand whether an exposure affects cancer recurrence, survival, or both. Although both end points are important in survivorship care, they may have different management implications. Finally, although a message that prediagnosis diet influences outcomes may seem to have limited utility for a patient when they develop cancer, it furthers the strength of the recommendation for people to maintain a healthy diet and lifestyle throughout their life to maximize the health benefits.

Source: JCO

HPV virus ‘linked to third of throat cancer cases’.

Posted by

1


One third of people diagnosed with throat cancer are infected with a form of the HPV virus, a study suggests.

HPV (human papillomavirus) is the major cause of cervical cancer, and the virus is known to spread through genital or oral contact.

Actor Michael Douglas is reported to have spoken about the link after his own diagnosis with throat cancer.

_68849303_hpv

Experts said this study in the Journal of Clinical Oncology, which quantifies the link, showed “striking” results.

There are more than 100 types of HPV. Most people will be infected with HPV at some point, but in most the immune system will offer protection.

There are two HPV strains which are most likely to cause cancer – HPV-16 and HPV-18.

HPV-16 is thought to be responsible for around 60% of cervical cancers, 80% of cancers in the anus and 60% of oral cancers.

Around 1,500 people are diagnosed with throat cancers each year in the UK, with around 470 people dying from the disease.

Survival benefit

This study looked at HPV’s link with cancer of the back of the throat – oropharyngeal cancer.

It looked at blood test results collected from people who took part in a huge prospective study into lifestyle and cancer, who were all healthy at the start.

Everyone gives a blood sample when they join the study, and in this case the researchers were able to check for the presence of antibodies to one of HPV’s key proteins – E6.

 “Start Quote

Condoms won’t stop infections completely.””

E6 knocks out part of cells’ protection system, which should prevent cancer developing.

Having the antibodies means HPV has already overcome that defence and caused cancerous changes in cells.

The researchers compared blood test results – some more than 10 years old – for 135 people who went on to develop throat cancer and for 1,599 cancer-free people.

The University of Oxford team found 35% of those with throat cancer had the antibodies, compared with fewer than 1% of those who were cancer-free.

However, these patients were more likely to survive throat cancer than people whose disease had other causes, such as alcohol or tobacco use.

The study found 84% of people with the antibodies were still alive five years after diagnosis, compared with 58% of those without.

Broader effect?

Dr Ruth Travis, a Cancer Research UK scientist at Oxford who worked on the study, said: “These striking results provide some evidence that HPV-16 infection may be a significant cause of oropharyngeal cancer.”

Sara Hiom, Cancer Research UK’s director of health information, said: “HPV is an extremely common virus.

“Practising safer sex may reduce the risk of getting or passing on HPV, but condoms won’t stop infections completely.”

She added: “If the HPV vaccine can also protect against oral HPV infections and cancers, then it could have a broader potential protective effect, but we don’t have enough research yet to tell us. ”

Source: BBC

Evaluation of Human Papillomavirus Antibodies and Risk of Subsequent Head and Neck Cancer.

Posted by

0


Abstract

Purpose Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.

Methods We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.

Results HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.

Conclusion HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.

Source: JCO

 

Alcohol consumption has no impact on breast cancer survival, according to new research.

Posted by

0


However, breast cancer survivors who consume alcohol in moderation may have a reduced risk of dying from heart disease

Although previous research has linked alcohol consumption to an increased risk of developing breast cancer, a new study has found that drinking before and after diagnosis does not impact survival from the disease. In fact, a modest survival benefit was found in women who were moderate drinkers before and after diagnosis due to a reduced risk of dying from cardiovascular disease, a major cause of mortality among breast cancer survivors.

The study results will be published in the April 8 edition of the Journal of Clinical Oncology. Polly Newcomb, Ph.D., a member of the Public Health Sciences Division and head of the Cancer Prevention Program at Fred Hutchinson Cancer Research Center, led the study.

“Our findings should be reassuring to women who have breast cancer because their past experience consuming alcohol is unlikely to impact their survival after diagnosis,” said Newcomb. “This study also provides additional support for the beneficial effect of moderate alcohol consumption with respect to cardiovascular disease.”

The study was based on data from almost 23,000 women with breast cancer who participated in theCollaborative Breast Cancer Study, a National Cancer Institute-sponsored, multi-site, population-based study of risk factors for breast cancer, and the largest such study of its kind. The study began in 1988 and was conducted in New Hampshire, Massachusetts and Wisconsin. In a smaller follow-up study between 1998 and 2001, about 5,000 study participants with breast cancer were also sent a follow-up questionnaire about their alcohol consumption habits after diagnosis.

Among study participants with a history of breast cancer, the authors found that the amount and type of alcohol a woman reported consuming in the years before her diagnosis was not associated with her likelihood from dying from breast cancer. However, the authors also found that those who consumed a moderate level of alcohol (three to six drinks per week) in the years before their cancer diagnosis were 15 percent less likely to die from cardiovascular disease than non-drinkers. Moderate wine consumption in particular was associated with a lower risk of cardiovascular disease mortality, while no such benefit was evident for consumption of beer or spirits, or for heavier levels of alcohol consumption.

Similar patterns were evident when considering reported alcohol consumption after breast cancer diagnosis. The amount and type of alcohol a woman consumed after diagnosis did not appear to be associated with survival of breast cancer, but those who consumed alcohol in moderation experienced a 40- to 50-percent lower mortality rate from cardiovascular disease.

What could account for the difference in alcohol’s impact on developing breast cancer risk and on survival from the disease? “It could be that the kind of breast cancer that is more likely to be diagnosed among women who drink may be more responsive to hormone-modifying therapies,” Newcomb said. Alcohol consumption is believed to influence breast cancer risk through increases in estrogen production in both pre- and post-menopausal women.

Funding for the study was provided by grants from the National Cancer Institute and Komen for the Cure. Co-authors included researchers from the University of Wisconsin Paul B. Carbone Comprehensive Cancer Center, Wageningen University in the Netherlands, H. Lee Moffitt Cancer Center, Norris Cotton Cancer Center, the University of North Carolina Lineberger Cancer Center and Research Institute, and Harvard Medical School and Brigham and Women’s Hospital.

 

Source: Fred Hutchinson Cancer Research Center

 

Cancer Trials Can Lack Clear Information on Biopsies.

Posted by

1


 Cancer drug trials often require participants to receive invasive procedures like biopsies, which are used to assess the drug’s effectiveness but have no therapeutic value – and can pose serious risks — for the patient.

Informed consent documents are supposed to inform study participants about these types of risks so they can make an educated decision on whether or not to participate in the trial, but a new study found this type of risk information to be seriously lacking.

Risks of Biopsies Not Clearly Stated

Writing in the Journal of Clinical Oncology, researchers stated:1

“A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.”

This was their conclusion after finding that more than 5 percent of biopsies in cancer drug trials may cause complications, but the informed consent documents did not adequately explain this. In fact, on average the consent documents had only 39 words addressing risks from invasive biopsies – less than the number of words used to address risks for simple blood draws.

Of the 745 tumor biopsies reviewed for the study, 39 resulted in complications, including lung air leaks, bleeding and other major effects that required hospitalization or surgery.

Whether you’re participating in a drug trial, or considering a biopsy for another medical reason, you should know that while biopsy risks are rarely discussed, there are risks, indeed.

Serious Biopsy Complications Every Patient Should Know

During a biopsy, a piece of tissue from a tumor or organ is removed so that it can be examined under a microscope, often to determine if it is cancerous. Needle biopsies, for instance, are widely used as part of the traditional allopathic approach to diagnosing breast cancer. But they may accidentally cause malignant cells to break away from a tumor, resulting in its spreading to other areas of your body.

According to a study from the John Wayne Cancer Institute, it appears that a needle biopsy may increase the spread of cancer by 50 percent compared to patients who receive excisional biopsies, also known as lumpectomies.2

The procedure also involves a serious risk of infection. For prostate gland biopsies, specialists have begun to worry about a recent, significant increase in hard-to-treat bloodstream infections that can require weeks of treatment.

Prostate biopsies inherently pose a risk for infection because:

  • The needles that collect a tiny piece of prostate tissue can transport bacteria through your rectal wall into the prostate and bloodstream
  • The needles can spread harmful bacteria present in your gut into your bloodstream

Pain, bleeding (that can be so severe it requires a blood transfusion or surgery to stop it), infection and accidental injury to a nearby organ are established risks that are present no matter what type of biopsy you receive. And then there is the issue of its questionable effectiveness.

In the case of prostate biopsies, an estimated one-third of men who receive “negative” results for prostate cancer actually do have prostate cancer that was missed by the biopsy. For breast biopsies, estimates suggest that 17 percent of D.C.I.S. (ductal carcinoma in situ) cases found through needle biopsy are misdiagnosed. And oftentimes it is an inaccurate mammogram (mammograms carry a first-time false positive rate of up to 6 percent) that leads to the breast biopsy in the first place, making the procedure completely unnecessary.

So, certainly if you’re considering taking part in a drug trial, you need to carefully assess whether the biopsy risks are worth it to you … and this is also true anytime you’re faced with a recommendation of a biopsy. You must measure the potential benefits against the risks in order to make an informed decision.

5,000 Combinations Of 100 Existing Cancer Drugs Tested To Find More Effective Treatments

Whereas biopsies are one of the go-to procedures conventional medicine uses to diagnose cancer, chemotherapy is the go-to procedure to treat it. But one of the reasons why conventional cancer treatment is such a dismal failure in the United States is because it relies on chemotherapy. Despite its reputation as the gold-standard in cancer treatment, chemotherapy has an average 5-year survival success rate of just over 2 percent for all cancers, according to a study published in the journal Clinical Oncology.3

The researchers concluded:

“ … it is clear that cytotoxic chemotherapy only makes a minor contribution to cancer survival. To justify the continued funding and availability of drugs used in cytotoxic chemotherapy, a rigorous evaluation of the cost-effectiveness and impact on quality of life is urgently required.”

It’s no secret among the cancer industry that these drugs are often ineffective, or that oftentimes the cancer patient survives not because of — but despite — the treatment. Moreover, it’s now common for treatments to use combinations of drugs, as many cancers have become resistant to single drugs, rendering them useless. Chemotherapy often supports the more chemo-resistant and malignant cell subpopulations within tumors (e.g. cancer stem cells), as it kills both the more benign cells and/or senescent cells within the tumor that keep it slow-growing, or even harmless.

As a result, this unleashes a more aggressive, treatment-resistant type of cancer to wreak havoc on the body.

A new study recently tested 5,000 combinations of the 100 cancer drugs approved for use in patients in an attempt to find more effective treatments.4 They plan to move several of their novel combinations into clinical trials as quickly as possible, but is this really going to benefit cancer patients?

Chemo Drugs Destroy Your Healthy Cells, Including Your Immune System

Chemotherapy drugs are, by their very nature, extremely toxic and typically work against your body’s natural ability to fight cancer by harming your immune system (often irreparably) instead of supporting it. Combining them into new formulations could cause any number of unforeseen consequences. Already, it’s known that certain chemo drugs become so toxic when combined that they would have to be used at such a low dose they would no longer work against the cancer!

And one of the biggest drawbacks to chemotherapy of any kind is the fact that it destroys healthy cells throughout your body right along with cancer cells, a “side effect” that often leads to accelerated death, not healing.

Another study, “The National Confidential Enquiry into Patient Outcome and Death (NCEPOD)”, found that more than four in 10 patients who received chemotherapy toward the end of life experienced potentially fatal effects. And after reviewing data from over 600 cancer patients who died within 30 days of receiving treatment, it was found that chemotherapy hastened or caused death in 27 percent of those cases.

In the last 30 years the global cancer burden has doubled, and it will likely double again between 2000 and 2020, and nearly triple by 2030 — unless people begin to take cancer prevention seriously. We CAN turn this trend around, but to do so the medical community must stop overlooking the methods that can actually have a significant impact.

Why I Strongly Advise Avoiding Chemotherapy

I strongly advise everyone to avoid taking any chemotherapy drugs. In my experience the people who survive the chemotherapy do it in spite of the therapy not because of it. More typically, once a person starts chemo it can lead to death. It is the one form of cancer therapy that I strongly advise most to avoid.

Why?

Because the way your body fights cancer normally is through a healthy immune system, and if you take drugs to target and destroy your immune system you tend to radically reduce your likelihood of long-term survival. This is not the case for surgery and radiation, which although also overused, do not impair your immune system and may debulk the tumor enough to give your immune system a chance to fight it.

Please also be aware that avoiding chemo comes with massive responsibility and the need to do something positive. Typically this involves a radical application of my advanced nutrition plan in addition to severely limiting protein and carbs and using high-quality fats as a source of calories. This would include foods like avocados, coconut oil, butter, nuts, olive and olive oil. This will tend to lower the mTOR pathway and optimize leptin and insulin signaling.

Four Must-Know Tips for Cancer Prevention

If you’re facing a health challenge, I recommend seeking out a qualified natural health consultant. When it comes to cancer, you’ll want to identify someone that is well known and respected for their work in treating cancer patients. If you don’t find someone locally then scour the Internet and make calls to plenty of patients that the practitioner has seen.

For the rest of you, focusing on cancer prevention is essential. Here are four advancements that have not yet been accepted by conventional medicine, but are extremely powerful cancer preventive tools nonetheless:

1.  Avoid Fructose and Sugar

It’s quite clear that if you want to avoid cancer, or are currently undergoing cancer treatment, you absolutely MUST avoid all forms of sugar — especially fructose — and this is largely due to its relation to insulin resistance.

According to Lewis Cantley, director of the Cancer Center at Beth Israel Deaconess Medical Center at Harvard Medical School, as much as 80 percent of all cancers are “driven by either mutations or environmental factors that work to enhance or mimic the effect of insulin on the incipient tumor cells,” Gary Taubes reported,5 adding:

“As it was explained to me by Craig Thompson, who has done much of this research and is now president of Memorial Sloan-Kettering Cancer Center in New York, the cells of many human cancers come to depend on insulin to provide the fuel (blood sugar) and materials they need to grow and multiply. Insulin and insulin-like growth factor (and related growth factors) also provide the signal, in effect, to do it.

The more insulin, the better they do.

Some cancers develop mutations that serve the purpose of increasing the influence of insulin on the cell; others take advantage of the elevated insulin levels that are common to metabolic syndrome, obesity and type 2 diabetes.

Some do both.

Thompson believes that many pre-cancerous cells would never acquire the mutations that turn them into malignant tumors if they weren’t being driven by insulin to take up more and more blood sugar and metabolize it.”

Some cancer centers, such as the Cancer Centers of America, have fully embraced this knowledge and place their patients on strict low-sugar, low-grain diets. But conventional medicine in general has been woefully lax when it comes to highlighting the health dangers of this additive.

As a standard recommendation, I strongly advise keeping your TOTAL fructose consumption below 25 grams per day, including fruits. But for most people it would also be wise to limit your fructose from fruit to 15 grams or less, as you’re virtually guaranteed to consume “hidden” sources of fructose if you drink beverages other than water and eat processed food.

2.  Optimize Vitamin D

There’s overwhelming evidence pointing to the fact that vitamin D deficiency plays a crucial role in cancer development. Researchers within this field have estimated that about 30 percent of cancer deaths — which amounts to 2 million worldwide and 200,000 in the United States — could be prevented each year simply by optimizing the vitamin D levels in the general population.

On a personal level, you can decrease your risk of cancer by MORE THAN HALF simply by optimizing your vitamin D levels with sun exposure. And if you are being treated for cancer it is likely that higher blood levels — probably around 80-90 ng/ml — would be beneficial.

If the notion that sun exposure actually prevents cancer is still new to you, I highly recommend you watch my one-hour vitamin D lecture to clear up any confusion. It’s important to understand that the risk of skin cancer from the sun comes only from excessive exposure.

3.  Decrease Protein

Ideally your protein level should be around one gram of protein per pound of lean body mass. Be very careful not to exceed this level and be assiduous about calculating and following this important recommendation. If you exceed this level of protein you will activate your mTOR pathway, which has been strongly correlated with promoting tumor growth.

4.  Exercise

If you are like most people, when you think of reducing your risk of cancer, exercise doesn’t immediately come to mind. However, there is some fairly compelling evidence that exercise can slash your risk of cancer. One of the primary ways exercise lowers your risk for cancer is by reducing elevated insulin and blood sugar levels, which creates a microenvironment that discourages the growth and spread of cancer cells.

If you have cancer, exercising during and after cancer treatment can reduce your risk of dying from cancer; reduce your risk of cancer recurrence; boost energy; and minimize the side effects of conventional cancer treatment.6

It’s important to include a large variety of techniques in your exercise routine, such as strength training, aerobics, core-building activities, and stretching. Most important of all, however, is to make sure you include high-intensity, burst-type exercise, such as Peak Fitness.

Source: Dr. Mercola

Drug Targeting Tumor Suppressor Shows Promise in First Human Study.

Posted by

0


An experimental drug that reactivates mutant forms of the tumor suppressor protein p53 is safe for humans, according to results from a phase I trial. The drug, APR-246, also stimulated signaling pathways that control p53 in tumor cells isolated from peripheral blood.

The study, published in the Journal of Clinical Oncology, was led by Dr. Sören Lehmann of Karolinska University Hospital in Stockholm.

The findings represent “a major step forward in targeting the most frequently altered pathway in cancer,” wrote Drs. Brian D. Lehmann and Jennifer A. Pietenpol of Vanderbilt University School of Medicine in an accompanying article.

The p53 protein suppresses tumor growth by increasing the expression of genes that slow the cell cycle, that prevent cells from dividing, or that cause programmed cell death (apoptosis). At least half of all tumors develop inactivating mutations in TP53, the gene that produces p53, allowing the tumor to evade this regulation. APR-246 counteracts TP53 mutations by restoring the gene-regulatory activity of mutant p53 protein and by inducing the death of cancer cells.

The 22 participants enrolled in the trial had various forms of leukemia, hormone-refractory metastatic prostate cancer, non-Hodgkin lymphoma, or multiple myeloma. These patients were included because prostate cancers have a high rate of TP53 mutations and because, in preclinical studies, leukemia cells were particularly sensitive to drugs that target p53.

The patients received intravenous infusions of APR-246 for 4 consecutive days. After a follow-up period of 17 days, the most common side effects were fatigue, dizziness, headache, and confusion.

While the trial was not designed to assess the drug’s antitumor effects, several patients showed clinical responses. To investigate the biologic activity of APR-246, Dr. Lehmann and his colleagues analyzed circulating tumor cells obtained before and after the 4-day treatment from the six patients who had these cells. Four of these patients had fewer proliferating cells after receiving APR-246. The investigators also observed signs of apoptosis and increased expression of several p53 target genes.

Microarray analysis of RNA isolated from the circulating tumor cells showed changes in genes responsible for regulating cell growth and death. The level of expression of genes that promote apoptosis appeared to correlate with the dose of APR-246.

Trials are being designed to investigate the effects of higher exposures to APR-246 through longer infusion times and of combining APR-246 with other chemotherapy drugs, most of which depend on a functional version of p53 to be effective.

Source: NCI

Aspirin Linked to Reduced Mortality in Prostate Cancer.

Posted by

0


In men who’ve undergone treatment for localized prostate cancer with radical prostatectomy or radiotherapy, aspirin use is associated with reduced prostate cancer mortality, researchers report in the Journal of Clinical Oncology.

Nearly 6000 men treated for localized prostate cancer were identified from a U.S. cancer registry. About one third took anticoagulants (aspirin, clopidogrel, enoxaparin, or warfarin) at some point during roughly 6 years’ follow-up, with aspirin being most commonly used.

Overall, prostate cancer mortality was significantly lower among anticoagulant users than nonusers (actuarial 10-year risk estimate, 3% vs. 8%). Patients with high-risk disease derived the greatest benefit. In subanalyses according to anticoagulant type, a significant risk reduction was seen only with aspirin (adjusted hazard ratio, 0.43).

The researchers note that coagulation plays a role in metastasis. They hypothesize, then, that aspirin’s effects on platelet aggregation may offer protection against metastasis.

Source: Journal of Clinical Oncology

 

Radioimmunotherapy Consolidation for Mantle Cell Lymphoma.

Posted by

0


A high response rate was achieved with limited cycles of R-CHOP followed by a single dose of 90Yibritumomab tiuxetan.

High overall and complete response rates can be achieved with six to eight cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with mantle cell lymphoma (MCL), but median response duration is only 18 to 24 months.

Given the high activity of radioimmunotherapy (RIT) in patients with relapsed MCL (J Clin Oncol 2009; 27:5213), investigators conducted a multicenter phase II trial to test the efficacy and safety of four cycles of R-CHOP plus yttrium-90 (90Y)–ibritumomab tiuxetan RIT consolidation in patients with previously untreated MCL.

Of 56 treatment-naive adults (median age, 60; 73% men; 91% with stage III–IV disease; 48% with extranodal involvement), 52 received four cycles of R-CHOP followed by a single dose of standard 90Y-RIT. The overall response rate was 82%, and response improved to complete or partial remission in 22 patients after 90Y-RIT. At a median follow-up of 72 months, the median time to treatment failure was 34.2 months; median overall survival (OS) had not been reached. The estimated 5-year OS rate trended higher for patients aged 65 versus those >65 (79% vs. 62%; P=0.08). Toxicities were as expected with R-CHOP and were primarily transient neutropenia and thrombocytopenia for 90Y-RIT.

Comment: Given the typically short duration of progression-free survival after immunochemotherapy in MCL patients, postinduction strategies are under study to improve outcomes. In younger patients, high-dose chemotherapy and autologous stem-cell transplantation are often utilized, whereas older or infirm patients might benefit from maintenance rituximab (JW Oncol Hematol Aug 21 2012). The present study confirms 90Y-RIT as an active agent that increases response rate and duration following abbreviated induction cycles, although without an established survival benefit as yet. Confirmatory studies will be important, as will optimizing patient selection for 90Y-RIT versus alternative postinduction regimens.

Source: Journal Watch Oncology and Hematology

Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer.

Posted by

0


Findings of a recent study, the largest and longest of its kind, provide strong evidence supporting a conservative approach to managing prostate cancer in some men. The study was not a randomized clinical trial; rather, it was a long-term analysis of a cohort of men diagnosed with what is called very-low-risk prostate cancer. Instead of immediately undergoing surgery or radiation therapy, the men had opted to undergo a process known as active surveillance at the Johns Hopkins University School of Medicine.

A diagnosis of very-low-risk prostate cancer means that the disease is highly unlikely to become a clinically significant, life-threatening cancer. These men could be safely monitored by active surveillance, the study found, with only a modest percentage eventually requiring some form of treatment and none dying from prostate cancer. The results were published online April 4 in the Journal of Clinical Oncology (JCO).

As is the case with prostate cancer in general in the United States, most of the men in the study were 65 or older. The results provide very strong evidence that active surveillance is the “preferred option” for most men in this age group with very-low-risk disease, said the study’s senior investigator, Dr. H. Ballentine Carter. In fact, he continued, “The overwhelming evidence says that for men over 65 who are diagnosed with low-risk disease, their first question should be whether any therapy is appropriate for them, not which therapy.”

The clinical relevance of the findings is hard to overstate, Dr. Carter stressed. Among the 217,000 men in the United States diagnosed each year with prostate cancer, a substantial proportion has very-low-risk or low-risk disease. The vast majority of these men immediately undergo some form of treatment, including men aged 75 and over, despite the fact that many would be unlikely to experience significant symptoms, let alone die from prostate cancer.

Defining Very-Low-Risk Prostate Cancer

The Johns Hopkins definition of very-low-risk prostate cancer is similar to the NCCN definition. For the study in JCO, very-low-risk was defined as:

  • Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
  • Gleason score of 6 or less
  • PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL or less
  • Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core

Patient Selection, Compliance Are Key

At Hopkins, the active surveillance program involves a semi-annual check-up and an annual biopsy. Patient selection is very important, Dr. Carter explained.

Among the 769 men enrolled in Hopkins’ active surveillance program between 1995 and 2010, approximately 80 percent had very-low-risk disease. Whether a patient has very-low-risk disease is determined based on factors such as the Gleason score (a common measure of tumor aggressiveness) and the extent of cancer in the biopsy samples, or cores, from the prostate gland. (See the sidebar for all of the factors.)

The remaining men had at least one biopsy feature that precluded their disease from being considered very-low-risk, Dr. Carter explained. These men were typically older and had other health problems, he continued, which made active surveillance more attractive than treatment with surgery or radiation, both of which can have significant side effects.

Compliance with the approach has been quite strong, the Hopkins team reported, with nearly 90 percent of participants completing their annual biopsies.

Although no men in the study died of prostate cancer, 255 did undergo some form of treatment, 74 percent of whom did so because their disease was reclassified based on the findings of an annual biopsy.

Overall, 41 percent of men in the study did not require any form of treatment, even after 10 years of follow-up, a “remarkable” finding, said Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis. “This study adds to the accumulating evidence that, in carefully selected patients, active surveillance is safe.”

The results “strongly support” recent revisions to prostate cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN), said the guidelines’ panel chair, Dr. James Mohler from the Roswell Park Cancer Institute. Updated last year, the guidelines recommend that physicians advise men with very-low-risk disease who have a life expectancy of up to 20 years to pursue active surveillance.

Findings like these on active surveillance, combined with related research on the growing problem of overdiagnosis and overtreatment of prostate cancer linked to PSA screening, appear to be reaching down into the community setting, Dr. Mohler believes.

“I think men and their doctors are becoming more educated about the overtreatment issue,” he said.

As evidence, Dr. Mohler pointed to the START trial, a phase III clinical trial being led by NCI-Canada, in collaboration with the U.S. NCI, in which men diagnosed with very-low-risk or low-risk disease are being randomly assigned to active surveillance or immediate treatment. When the trial opened in 2007, most men who declined to enroll did so because they did not want to take the risk of being assigned to the active surveillance arm. “Now most men are declining to participate because they want active surveillance,” Dr. Mohler said.

Having a strong system in place to ensure that men pursuing active surveillance are followed and receive reminders for their check-ups and biopsies is extremely important, Dr. Carter stressed.

At the moment, the Hopkins surveillance program is managed primarily by an administrator using a manual process. But the program is moving to a Web-based approach for monitoring and following patients, he added.

Approaches Can Vary

Although the evidence in favor of active surveillance continues to accumulate, the optimal approach to managing the process is not yet defined, Dr. Mann noted. This is particularly true with respect to how patients’ disease is tracked.

At Hopkins, men are followed via check-ups and annual biopsies. Any reclassification of their disease is typically based on biopsy findings, such as a change in Gleason score, which might then produce a recommendation for treatment. But many other centers, such as Roswell Park, do not require men who choose active surveillance to undergo regular biopsies. Rather, they use some form of what is commonly called PSA kinetics, which are changes in PSA levels over time (for instance, how long it takes for PSA levels to double).

Results from several studies, however, have raised doubts about the value of PSA kinetics in initially identifying or managing prostate cancer. Based on their experience, PSA kinetics is “not reliable for predicting the presence of high-grade cancer on an individual basis,” the Hopkins team wrote in JCO. “Thus, if the goal of surveillance is to identify and treat higher-risk cancers, we believe that annual biopsies may be necessary to ensure patient safety.”

But regular biopsies are by no means without their own risks. A small percentage of men end up in the hospital with antibiotic resistant infections as a result of a prostate biopsy, Dr. Mohler said, and repeat biopsies can lead to inflammation and scar tissue formation that can preclude nerve-sparing surgery to treat the prostate cancer in some men whose disease progresses.

According to Dr. Carter, Hopkins researchers are now studying whether men who have had two consecutive biopsies that show no evidence of disease progression can safely have the interval between routine biopsies extended. In the meantime, the NCCN guidelines are being revised again, Dr. Mohler said, using data from large active surveillance programs at Hopkins, the University of Toronto, and the University of California, San Francisco, to provide recommendations on managing men who choose this conservative approach.

Further clarity on this matter should be forthcoming, Dr. Mann said. In addition to the START trial, which will follow men using both PSA measures and prostate core biopsies, a similar trial is being conducted in the United Kingdom that is using only PSA levels to monitor patients. Also, in December, NCI and CDC are sponsoring an NIH State-of-the-Science Conference to review the role of active surveillance in managing localized prostate cancer and to help guide future research in this area.

Source: NCI.