Last week, the U.S. Food and Drug Administration (FDA) approved a new combination of drugs, formulated together in a single pill called Lonsurf (previously known as TAS-102), to treat patients with advanced colorectal cancer that is no longer responding to other treatments after the treatment was shown in a double-blind, placebo-controlled, phase III clinical trial to extend overall survival.
Advances against colorectal cancer were urgently needed because even though screening has helped dramatically reduce incidence and mortality rates, the disease remains the second-leading cause of cancer-related death in the United States.
The two drugs in the new pill—trifluridine and tipiracil—work together to exert an anticancer effect. Trifluridine is the cytotoxic chemotherapeutic component of TAS-102, causing damage to DNA, which can ultimately trigger cell death, while tipiracil prevents rapid breakdown of trifluridine, thereby maintaining adequate levels of the trifluridine in the body.
Trifluridine is a nucleoside analogue, which means it is very similar to the basic building blocks of DNA. Upon entering the body, trifluridine can be modified by a process called phosphorylation. After this, because of its similarity to the building blocks of DNA, it can be incorporated into DNA. However, because it is not a true DNA building block, this results in abnormal DNA; this has beenreported to be the main mechanism by which TAS-102 causes DNA damage.
Other DNA building block analogues, such as fluorouracil, have been a mainstay of cancer chemotherapy for decades. However, in the phase III clinical trial that led to the FDA approval of TAS-102, results of which were published inThe New England Journal of Medicine, the new combination chemotherapeutic pill extended survival even for those patients who had colorectal cancer that was no longer responding to treatment with fluorouracil-containing treatments.
With several ongoing clinical trials evaluating TAS-102 as a treatment for other types of cancer, we will likely learn more about the potential for this chemotherapeutic-containing agent to benefit a wider group of patients in the near future.
Drug companies have a problem: they are finding it ever harder to get painkillers through clinical trials. But this isn’t necessarily because the drugs are getting worse. An extensive analysis of trial data has found that responses to sham treatments have become stronger over time, making it harder to prove a drug’s advantage over placebo.
The change in reponse to placebo treatments for pain, discovered by researchers in Canada, holds true only for US clinical trials. “We were absolutely floored when we found out,” says Jeffrey Mogil, who directs the pain-genetics lab at McGill University in Montreal and led the analysis. Simply being in a US trial and receiving sham treatment now seems to relieve pain almost as effectively as many promising new drugs. Mogil thinks that as US trials get longer, larger and more expensive, they may be enhancing participants’ expectations of their effectiveness.
Stronger placebo responses have already been reported for trials of antidepressants and antipsychotics, triggering debate over whether growing placebo effects are seen in pain trials too. To find out, Mogil and his colleagues examined 84 clinical trials of drugs for the treatment of chronic neuropathic pain (pain which affects the nervous system) published between 1990 and 2013.
Based on patients’ ratings of their pain, the effect of trialled drugs in relieving symptoms stayed the same over the 23-year period—but placebo responses rose. In 1996, patients in clinical trials reported that drugs relieved their pain by 27% more than did a placebo. But by 2013, that gap had slipped to just 9%. The phenomenon is driven by 35 US trials; among trials in Europe, Asia and elsewhere, there was no significant change in placebo reponses.The analysis is in press in the journal Pain.
Only in America
This effect would explain why drug companies have trouble getting new painkillers through trials, notes neuroscientist Fabrizio Benedetti, who studies placebo responses at the University of Turin, Italy. Over the past ten years, he says, more than 90% of potential drugs for treatment of neuropathic and cancer pain have failed at advanced phases of clinical trials.
But the finding that placebo responses are rising only in the United States is the most surprising aspect of the latest analysis. One possible explanation is that direct-to-consumer advertising for drugs—allowed only in the United States and New Zealand—has increased people’s expectations of the benefits of drugs, creating stronger placebo effects. But Mogil’s results hint at another factor. “Our data suggest that the longer a trial is and the bigger a trial is, the bigger the placebo is going to be,” he says.
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Longer, bigger US trials probably cost more, and the glamour and gloss of their presentation might indirectly enhance patients’ expectations, Mogil speculates. Some larger US trials also use contract research organizations that can employ nurses who are dedicated to the trial patients, he adds—giving patients a very different experience compared to those who take part in a small trial run by an academic lab, for instance, where research nurses may have many other responsibilities.
No pain, no gain?
Mogil’s data also challenge one of the fundamental principles of placebo-controlled trials—that comparing a drug against placebo tells us how well a drug works. A basic principle of these trials is that drug and placebo effects are additive: our total response to any drug we take is equal to the placebo response plus the drug’s biochemical effect. But Mogil found that although placebo responses have increased over time, drug responses haven’t risen by the same amount.
That suggests placebo and drug responses may not always be strictly additive. This isn’t entirely unexpected, Mogil argues, because both placebos and pharmaceutical painkillers tap into similar biological mechanisms—such as the release of endorphins in the brain. But if true, it suggests that growing placebo responses are masking real painkilling effects. “There are a lot of people in the pain field who believe the drugs that are failing clinical trials actually work, it’s just that the trials can’t show it,” he says.
For companies trying to develop treatments, one remedy might be to compare new drugs against their best competitors instead of against placebo—or to go back to conducting smaller, shorter trials. Benedetti is not convinced, however. “I don’t think that controlling the placebo response will increase the number of successful trials,” he says. “What drug companies have to do is to find more effective drugs.”
Mogil suggests it is also worth investigating the elements that generate the more powerful placebo response in US trials, and then incorporating those elements (such as the relationship between patient and nurse) into patient care. Ted Kaptchuk, director of placebo research at Harvard Medical School in Boston, Massachusetts, agrees. “If the major component of a drug in any particular condition is its placebo component, we need to develop non-pharmacological interventions as a first-line response,” he says.
Teens who spend hours on the Internet may be at risk for high blood pressure and weight gain, researchers say.
Researchers found that teens who spent at least 14 hours a week on the Internet had elevated blood pressure. Of 134 teens described by researchers as heavy Internet users, 26 had elevated blood pressure.
This is believed to be the first study to show a link between time spent on the Internet and high blood pressure.
The findings add to growing research that has shown an association between heavy Internet use and other health risks like addiction, anxiety, depression, obesity and social isolation, researchers said.
“Using the Internet is part of our daily life but it shouldn’t consume us. In our study, teens considered heavy Internet users were on the Internet an average of 25 hours a week,” said Andrea Cassidy-Bushrow, a researcher at Henry Ford’s Department of Public Health Sciences.
“It’s important that young people take regular breaks from their computer or smartphone, and engage in some form of physical activity. I recommend to parents they limit their children’s’ time at home on the Internet. I think two hours a day, five days a week is good rule of thumb,” Cassidy-Bushrow said.
Researchers analysed data compiled from 335 teens ages 14-17 enrolled in the study including a blood pressure reading taken during a physical exam.
Participants also completed a 55-question survey of their Internet use during the week leading up to their physical exam. Questions ranged from how they spent their time on the Internet and their number of email addresses to time spent on the Internet daily and for what purpose.
For their study, researchers defined Internet use as visiting web sites, emailing, instant messaging, playing games, doing homework, shopping, downloading software and creating or maintaining webpages.
The study also found that teens spent on average 15 hours a week on the Internet at either school or home and 39 per cent of girls were heavy Internet users compared to 43 per cent of boys.
Researchers found that 43 per cent of heavy Internet users were considered overweight compared to 26 per cent of light Internet users.
Asking you to switch off all your gadgets is impractical. Hence, we got a doctor to give you tips on how to keep your eyes healthy in a highly screen-driven world.
Remember when your mother would ask you not to sit too close or spend too much time on the television screen? Well, that is now an almost impossible task. The digital world has made us swap the television with many other electronic devices and keeping our eyes strong is a challenge.
Many of us are glued to a screen, be it a work station desktop, a mobile or a tablet, for as long as 12-15 hours a day and this is definitely not healthy but inescapable. But we can certainly avert long-term damage to our eyes with some day-to-day lifestyle changes.
On World Eyesight Day today, we spoke to Dr Sanjay Dhawan, Director, Ophthalmology, Max Healthcare, who gave us easy tips on how to avoid eye strain and other related problems.
Blink more often: One tool to help evade eyestrain when working on a computer is to blink your eyes often, to reduce dryness.
Screen placement: Maintain a distance of 25 inches from the monitor, or more.
Follow the 20-second rule: It is suggested that you must take a 20-second break after every half an hour of screen use. Shifting your gaze to something in the distance during the break will also help relieve the strain.
Minimise glare: Using an anti-glare film on your monitor or hand-held devices will further omit harmful radiations.
Convergence exercises: Adequate amount of exercises can help you focus better and could also reduce the unnecessary stress that the eyes are put through. You can perform this by looking at a pencil placed close to your eyes and then moving it in a to and fro manner, keeping the focus in place.
Monitor tilt: Tilt your computer screen so that the top is slightly farther away from you than the bottom.
Use an LCD: Older CRT monitors are more likely to cause strain on your eyes than a liquid crystal display screen.
Get an annual eye examination: A regular check-up by an eye care professional is mandatory. However, after the age of 40, a 6 month check-up is suggested.
In addition to immune system support, zinc also aids in the growth and development of the body, beginning in infancy. It also maintains and restores healthy hair, skin and eyes. Zinc is necessary for collagen formation – that’s part of what makes hair and nails strong and keeps your skin wrinkle-free. In fact, white spots on your nails can denote deficiency. Zinc also promotes your immune system and accelerates wound healing through its role in cell function. It also aids in your digestive process and helps reduce bloating and inflammation. Zinc is also an excellent mood booster and promotes brain health.
Some excellent sources of zinc include beans, nuts, seeds, meat, fish, eggs, asparagus and sprouts. Food is always the best source of nutrients, as it is the most readily absorbed source. Supplementation should be discussed with a doctor to prevent possible complications from having too much zinc, as is possible with any mineral or vitamin.
And pays health leaders to say soda is healthy
Recent news has come out exposing Monsanto for trying to discredit any scientist who paints a less-than-rosy picture for biotech and GMO crops.
To join this play on the consumer conscience is a ploy from the international soda seller, Coca-Cola. Some claim that the company pays scientists who will shift the blame away from junk food diets and sugar-laden sodas for causing a global obesity epidemic, and numerous other serious health concerns.
In fact, Coca-Cola was caught paying ‘health leaders’ to say soda is a ‘healthy snack’ before.
Coca-Cola claims that it wants America to be fit. Really…
Does it seem ironic that one of the major contributors to the growing obesity rate around the world, Coca-Cola, gave $3 million in 2012 to Chicago’s Garfield Park Conservatory Alliance in order to begin a ‘wellness program’? The mega-corp also donates millions to strike down GMO labeling.
Here’s an idea for wellness – stop selling people drinks so full of GM sugar that they don’t get a single nutritional need met, while simply filling up on empty, calories. Not to take the focus off of our own responsibility to educate ourselves and eat better, but Coca-Cola heading a ‘wellness’ campaign is like Charles Manson trying to lead a workshop on how to get in touch with your ‘inner child.’
Yet, similar to the tactics used by Big Tobacco, Coca-Cola and other companies aligned with the Grocery Manufacturer’s Association simply use ‘science’ to persuade a nation to keep up with their sugar addictions.
These addictions are real. Consider Natasha Harris who died in 2013 from a cardiac arrhythmia, according to a 19-page coroner’s report. Harris, a mother of 8 from Invercargill, New Zealand, was known to smoke heavily and skip multiple meals, but coroner David Crerar concluded that the sugar and caffeine she got by drinking more than 2.6 gallons of Coca-Cola Classic per day was ‘the substantial factor’ in her death.”
We are supposed to forget facts like these with Coca-Cola’s new ‘science-based’ marketing campaign attempt to fancy up a ridiculous message which tells America to just move more, and worry less about the calories they consume. We learn from the New York Times articles (linked in the first paragraph) that:
“The beverage giant has teamed up with influential scientists who are advancing this message in medical journals, at conferences and through social media. To help the scientists get the word out, Coke has provided financial and logistical support to a new nonprofit organization called the Global Energy Balance Network, which promotes the argument that weight-conscious Americans are overly fixated on how much they eat and drink while not paying enough attention to exercise.”
That’s odd since a 12-oz can of Coke contains around 138 calories. This means that most people would have to walk almost an hour to burn off the calories in one Coke. This also ignores the fact that the sugar levels in Coke and the fake-sugars in Diet Coke are responsible for a host of other ailments aside from obesity – from insulin resistance to migraines.
Then there’s the dire consideration that found in a Danish study showing that men who drank 32 ounces or more of Coca-Cola daily could reduce their sperm count by nearly 30%, or that those who drink soda’s like Coca-Cola tend to eat less nutrition-filled fruits and vegetables.
Yes, the very same company that is launching a ‘science-based’ campaign for ‘wellness’ makes products which contain:
Phosphoric Acid (in Coca-Cola and Diet Coke) which has been shown to destroy bones by contributing to osteoporosis as well as damaging teeth.
Aspartame, now known as AminoSweet, whichhas been linked to numerous diseases and health problems.
Food dyes and other chemical additives that are known carcinogens.
GM Sugar – Want a reality check for how much sugar (often of the genetically modified variety) is in Coca-Cola?
This doesn’t even cover the questionable ‘wellness’ provided by products like Vitamin Water, which has been the subject of both a lawsuit, and subsequent settlement.
Or how about the California judge who has allowed a suit against the Coca Cola Company to proceed, despite Coke’s claims that the lawsuit is without merit. The plaintiffs are suing Coke, alleging that the following claim is false:
“No artificial flavors.
No preservatives added.
Why would this claim be false? Take a look at the ingredient list and you can decide:
‘Carbonated water, high fructose corn syrup, caramel color, phosphoric acid, natural flavors, caffeine.’”
So as we drink to our ‘health’ Steven N. Blair, an exercise scientist, says:
“Most of the focus in the popular media and in the scientific press is, ‘Oh they’re eating too much, eating too much, eating too much’ — blaming fast food, blaming sugary drinks and so on . . .and there’s really virtually no compelling evidence that that, in fact, is the cause.”
Sure, eating calorie-filled food with high sugar content, and carcinogenic ingredients – that’s a sure way to wellness – said NO ONE, EVER. Oh, wait, unless of course you work for Coca-Cola.
Many health experts are smart enough to know better. They warn that this message is misleading and irresponsible.
There are an estimated 2.8 million breast cancer survivors in the U.S., a testament to the more than 25-year decline in mortality, according to the American Cancer Society. Still, 231,000 women alone will be diagnosed with the disease this year, and about 40,000 will die.
These women will newly rely on targeted gene therapies, advancements in chemotherapy protocols and even preventive treatments. For breast cancer patients and their loved ones, the scientists who keep pushing the boundaries of what’s possible are heroes held in highest esteem.
Here are the five biggest breakthroughs in breast cancer research those scientists have made in 2015.
1. A NEW DRUG MAY STOP AN INCURABLE TYPE OF BREAST CANCER
The FDA granted accelerated approval to a drug called Palbociclib in February. When used with the breast cancer drug Letrozole in trials, Palbociclib was able to extend the amount of time study participants lived without their cancer progressing.
The cocktail was able to stop cancer progression in postmenopausal women with a treatable but incurable type of chronic breast cancer (ER-positive, HER2-negative advanced breast cancer) for an average of 20.2 months. A control group that only took Letrozole had an average of 10.2 months without cancer progression.
“It seemed to prolong the period of disease control significantly. More important is the promise it provides,” said Dr. Cliff Hudis, chief of breast medicine service at Memorial Sloan Kettering Cancer Center. “Maybe with more study, the drug will actually help people live longer; that’s the big answer we’re waiting for right now.”’
Hudis also praised Palbociclib because it is a less toxic form of treatment than chemotherapy. However, the FDA notes that serious side effects of the drug in combination with Letrozole include pulmonary embolism and diarrhea. Still, its approval is a heartening step for FDA watchdogs.
“The FDA approval strategy of breakthrough status and accelerated approval show the FDA’s commitment to getting promising drugs for serious diseases to patients faster,” said Dr. Julie Gralow, a member of the Fred Hutchinson Cancer Research Center and director of breast medical oncology at Seattle Cancer Care Alliance.
2. GENETIC TUMOR TESTING WILL TELL YOU IF CHEMOTHERAPY WILL WORK FOR YOU.
Researchers have known for some time now that a tumor’s genes can determine whether cancer patients will respond to chemotherapy. The Oncotype Dx test analyzes 21 genes in the tumor to determine whether or not the cancer is likely to recur, and whether or not chemotherapy will make a difference.
This test was created using historic data — old tumors that grew in patients for whom outcomes were already known. But in September, the New England Journal of Medicine carried the very first study using data from current patients; it confirms the Oncotype assay is able to predict which treatments would be most effective in early stage, curable breast cancer patients. This helps women avoid toxic and unpleasant chemotherapy if the test reveals their cancers will not respond to it.
In an editorial that accompanies the study, Hudis noted that this protocol spared 1,626 women from receiving unnecessary chemotherapy. Each of them would have been a candidate for it according to traditional diagnostic standards.
“The key thing is that they identified a group of people who are normally candidates for chemotherapy but had a 99 percent freedom from metastases at five years,” the typical benchmark for cancer survival, Hudis told HuffPost. “What it means practically is that some proportion of people who have been recommended to get therapy for years really don’t need it.”
3. LESS AGGRESSIVE CHEMOTHERAPY CAN STILL BE EFFECTIVE.
Doctors already know that super aggressive chemotherapy, used in combination with a drug called Trastuzumab (or by its brand name, Herceptin), works to cure an early stage but aggressive type of breast cancer known as lymph node negative HER2+ breast cancer, a type that affects 15 to 20 percent of all breast cancer patients.
But in a study published in January in the New England Journal of Medicine, researchers found that a much less aggressive chemotherapy drug called Taxol, used in combination with Trastuzumab, was just at effective in helping women stave off breast cancer recurrence and death after three years.
“This trial showed that we can use less aggressive chemotherapy (weekly taxol) in combination with Herceptin in lower risk Her2+ breast cancers and still get excellent outcomes,” explained Gralow. “Trial designs that require less patients and are done faster like this need to be considered in the future, and trials looking at reducing toxicity for patients are also critical.”
4. BONE STRENGTHENING MEDICATIONS CAN STOP BREAST CANCER’S SPREAD.
The most common place breast cancer will recur is in the bones, and research has gone back and forth on whether bone-strengthening medications called bisphosphonates, made to treat osteoporosis, can help prevent this.
Now, a meta-analysis of these studies published in the journal The Lancet confirms that these osteoporosis medications can reduce breast cancer recurrence in the bone and decrease deaths in postmenopausal women. Additionally, notes Gralow, the medications do what they were originally designed to do and have the added benefit of reducing fractures.
Hudis is more skeptical of the meta-analysis’ results, and notes that meta-analysis’ positive results were all in middle-aged people or older who are candidates for bisphosphonate medication anyway. Younger breast cancer patients will need to have a more in-depth discussion with their doctors, he said. As with all medications, bisphosphonates can have serious side effects, like osteonecrosis of the jaw — when the gum recedes and the jaw bone becomes exposed to air — or eye inflammation and severe musculoskeletal pain.
5. IMMUNOTHERAPY IS SHOWING MORE PROMISE IN THE TREATMENT OF INCURABLE CANCERS.
The odds are stacked against women with triple negative breast cancer, a type that accounts for 10-20 percent of all breast cancers. This kind of cancer is much more aggressive and alsomore likely to affect young women, black women, Latino women and those with the BRCA1 gene mutation, notes Johns Hopkins Medicine. As the name implies, these tumors do not have estrogen receptors, progesterone receptors or the HER2 growth factor, which means three avenues of targeted treatment are not an option for them. Only surgery, radiation therapy and chemotherapy can be deployed against this kind of tumor, and often to little effect, as the type is more likely to come back and spread.
But immunotherapy medication that activates a person’s own immune system against the tumor could one day be a promising therapy for triple negative breast cancer. For instance, a small study by Johns Hopkins researcher Dr. Leisha A. Emens found that an immunotherapy drug was able to halt the cancer’s progression for 24 weeks in 27 percent of participants. The study only had 54 participants, so the results are modest, but the drug’s promise is exciting. Emens presented the results of her study at the American Association for Cancer Research conference in April.
“It’s early days, but that’s an area of really exciting, ongoing and rapidly expanding research,” said Hudis. “If it works, it’ll represent something new and important for triple negative breast cancer.”
And it could be the key to slowing down or stopping progression of the disease.
An immune system gene that’s associated with a higher risk of Alzheimer’s disease has been identified by researchers in the US. Older adults and Alzheimer’s patients who are carrying a specific variant of the IL1RAP gene were found to have higher rates of amyloid plaque accumulation in the brain, which is one of the key drivers of the disease.
Not only could the discovery lead to quicker diagnoses and better identification of at-risk patients, but researchers suggest that by manipulating the IL1RAP immune pathway they could figure out how to either slow the progression of the disease, or perhaps stop it altogether.
“These findings suggest that targeting the IL1RAP immune pathway may be a viable approach for promoting the clearance of amyloid deposits and fighting an important cause of progression in Alzheimer’s disease,” said one of the team, Andrew Saykin from the Indiana University School of Medicine.
Previous research has linked another genetic factor to the development of Alzheimer’s disease – the APOE e4 allele. But when Saykin and his team imaged the brains of almost 500 volunteers via PET (positron emission tomography) scans, and assessed the levels of brain amyloid deposits at the time and then two years later, they found that the IL1RAP variant had an even stronger effect on the progression of the disease than APOE e4.
The gene IL1RAP codes for an immune signalling factor called the Interleukin-1 Receptor Accessory Protein, which triggers the production of pro-inflammatory proteins in response to infection, tissue damage, or stress. It also influences the activity of the microglia – a specific type of cell found in the brain and the spinal cord that acts as the first and main line of immune defence in the central nervous system.
The study, published in the journal Brain, found that over the two-year period, people carrying the IL1RAP variant had a lower level of microglial activity, which means the brain is less able to clear out protein build-up; a faster degeneration of the temporal cortex, which is the region of the brain involved with memory; and faster cognitive decline.
“This was an intriguing finding because IL1RAP is known to play a central role in the activity of microglia, the immune system cells that act as the brain’s ‘garbage disposal system’ and the focus of heavy investigation in a variety of neurodegenerative diseases,” said one of the researchers, Vijay K. Ramanan.
Regardless of whether a patient has APOE e4 too, the presence of the IL1RAP variant was associated with an overall greater likelihood of progression from mild cognitive impairment to Alzheimer’s disease.
But there is good news. The researchers think that treatments specifically targeting the IL1RAP immune pathway could increase the brain’s ability to clear out amyloid deposits in patients carrying the gene variant. And fortunately, drugs that target the so-called IL-1/IL1RAP pathway already exist for the treatment of various inflammatory conditions, which means clinical testing could be right around the corner.
“These findings suggest that targeting the IL1RAP immune pathway may be a viable approach for promoting the clearance of amyloid deposits and fighting an important cause of progression in Alzheimer’s disease,” said Saykin.