A study of a new drug for advanced skin cancer has shown it “almost doubles survival times”, BBC News has reported.
The drug, called vemurafenib, was tested in a clinical trial that examined its impact on tumour size and survival in patients with advanced melanoma skin cancer that had spread to other parts of the body. The outlook for this type of cancer is generally poor as it's an aggressive cancer with few treatment options and patients tend to survive for less than a year. Researchers found that approximately half of the patients responded to the drug and that the overall survival rate in these patients was nearly 16 months, on average.
This study provides evidence on the effectiveness of a new drug, vemurafenib, for treating some patients with metastatic melanoma. Because the drug works by targeting a specific genetic mutation, it won’t be suitable for patients who aren’t carrying the mutation, which is found in around half of patients with melanoma that has spread. Additionally, while the drug has been recommended for approval, it hasn't yet been approved for use in Europe; it is unclear at this point if and when it will be available for treatment in the UK, although the National Institute for Health and Clinical Excellence (NICE is said to be currently assessing it.
Where did the story come from?
The study was carried out by researchers from Vanderbilt University, the Hoffman-La Roche pharmaceutical company and other institutions throughout the US and Australia. The research was supported by Hoffmann-La Roche, who are the manufacturers of vemurafenib.
The study was published in the peer-reviewed New England Journal of Medicine.
The BBC covered this research appropriately, emphasising the positive results but also highlighting that the drug had yet to be approved in the UK and wouldn’t be suitable for all patients with metastatic melanoma. The broadcaster also reported on some of the limitations of the research methods.
What kind of research was this?
This was a phase II clinical trial that examined how effective a drug called vemurafenib was at inducing a clinical response and its impact on overall survival in a set of patients with metastatic melanoma. Malignant melanoma is a relatively rare but aggressive type of skin cancer that can be particularly hard to treat when caught at an advanced stage. All of the patients in the trial carried a specific genetic mutation called the “BRAF V600 mutation”, which leads to the abnormal activation of an enzyme involved in cell growth and death. Previous research indicates that vemurafenib blocks the action of this enzyme.
Phase II trials are designed to assess the effects of new drugs in highly controlled settings. These trials don’t normally employ a group of control patients receiving other forms of treatment, and so generally can’t be used to tell how a new drug compares against standard or existing treatments. These types of control-group comparisons are usually performed in phase III trials. Phase II trials are, however, a key part of the development of new drugs, and are used as a confirmatory step before a drug can be given to wider research populations.
Media coverage of this trial has compared the survival rates of patients receiving vemurafenib with those seen in general patients with metastatic melanoma, rather than patients directly involved in the study. While such comparisons are useful for readers to understand more about the drug, formal scientific comparisons of different treatments have to account for a range of important factors, such as patients’ medical histories or how advanced the cancer is when treatment is started.
What did the research involve?
Researchers enrolled 132 patients with stage IV metastatic melanoma (stage IV cancer means it has spread to other parts of the body, such as the lungs or liver . They all carried a form of BRAF V600 genetic mutation. All patients had previously been treated for the disease, and they all received the same dose of the drug vemurafenib twice a day. The patients stopped taking the drug if they experienced unacceptable side effects or if their disease progressed.
The patients underwent tumour imaging (either magnetic resonance imaging (MRI or computed tomography (CT at the beginning of the study and every six weeks thereafter. Researchers used these scans to assess any changes in tumour size and response to the treatment.
Researchers then analysed the data to determine the proportion of patients who responded to treatment.
What were the basic results?
The patients were followed up for an average (median of 12.9 months. The researchers found that:
- Overall, 53% of patients showed some reduction in the size of their tumour measured at the start of the study.
- Among those that responded, eight patients achieved a complete response (6% of the total study group , and 62 patients (47% achieved a partial response (47% of the total study group .
- Of the patients who responded to treatment, 23 (33% of responders maintained that response at the end of the study.
- The median duration of response was 6.7 months (95% CI 5.6 to 8.6 months .
- Median overall survival was 15.9 months (95% CI 11.6 to 18.3 months , and 62 patients (47% were still alive at the end of the study.
- The overall survival rate at six months was 77% (95% CI 70% to 85% , at twelve months was 58% (95% CI 49% to 67%, and at eighteen months was 43% (95% CI 33% to 53% .
Most patients experienced at least one side effect due to the study drug. The most commonly reported side effects were joint pain, rash, fatigue, sensitivity to light and hair loss. Four patients (3% stopped taking the drug due to side effects. One patient died due to a rapid progression of the melanoma along with kidney failure; the researchers said this may have been related to taking vemurafenib but this was not certain.
How did the researchers interpret the results?
The researchers concluded that vemurafenib effectively targets metastatic melanoma tumours in patients with BRAF V6000 mutations, and that response rates are higher than those seen with other treatments.
Conclusion
This study has shown that patients with a specific mutation and advanced metastatic melanoma have a high response rate to a new drug, vemurafenib. Currently, treatment options for people with metastatic melanoma can involve chemotherapy, radiotherapy or immune therapies, but even with treatment the outlook is usually poor once their cancer has spread. Often, people with late-stage disease may be enrolled in clinical trials such as this to try and find more effective treatments.
Researchers say that the long follow-up of their study provides initial evidence on the overall survival of patients receiving this drug, something that phase III studies have so far not been able to demonstrate.
Researchers point out, however, that patients do develop resistance to vemurafenib, and that further research is needed to determine how this occurs.
Previous studies have shown that patients with metastatic melanoma have an average survival rate of 6 to 10 months, as mentioned in some news coverage. However, it is difficult to compare this estimate to survival times seen in the current study, as the patient populations may be different. For example, it’s unclear whether these studies enrolled patients with the same genetic mutation, or how survival may be different between those with and without the mutation.
This study adds to the mounting evidence of the effectiveness of vemurafenib as a treatment of metastatic melanoma with BRAF V600 mutation. While this phase II study cannot directly demonstrate effectiveness compared to standard care, an additional phase III study has been conducted that randomised patients to receive vemurafenib or standard therapy. This study was stopped before it was complete, as an interim analysis indicated that vemurafenib significantly improved patients' progression-free survival and six-month survival, compared with standard care. At this point, all of the participants were given the new drug.
All in all, this is very promising research for the treatment of an aggressive cancer for which there are few existing options. At present the drug has been recommended for approval by the European Medicines Agency, and is currently being evaluated by NICE for use in the UK.
Analysis by Bazian
Links To The Headlines
Skin cancer drug hopes raised by study. BBC News, February 23 2012
Links To Science
Sosman JA, Kim KB, M.D., Schuchter L et al. Survival in BRAF V600 Mutant Advanced Melanoma Treated with Vemurafenib. New England Journal of Medicine 2012; 366:707-714
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While the testing program may be inexpensive, it's critical because no other federal mechanism currently exists to conduct regular testing of fresh produce. (The Food and Drug Administration--which technically has jurisdiction over produce safety--conducts only limited inspections.
To date, the MDP has
tested high-risk produce such as alfalfa sprouts, cilantro, green onions, peppers, tomatoes, spinach, and other leafy greens. Every one of these vegetables has caused a food-borne illness outbreak or recall over the years, some of them lethal thanks in part to an industrialized food system that transports bugs nationwide. You might recall, a shocking
34 people (and counting died from a listeria outbreak last year in cantaloupe in 26 states (yes, melon - also on USDA's tested produce list . That tragedy alone should cause the Obama Administration to rethink this thoughtless budget cut.
It's not like this is some wasteful government program. It's a relatively cheap way to help save lives, so what's going on? Here is how food safety attorney Bill Marler
explains who just might be behind the idea:
The produce industry hates this program as it has found pathogens in domestic and imported samples and FDA has responded to the information and recalled products. The produce industry--via the fruit and vegetable advisory committee--recommended to USDA and Congress that the program be terminated.
The produce industry hates the program? Now we're getting somewhere.
According to this AP
story, lobbyists with the United Fresh Produce Association and other major trade associations "have repeatedly pushed the government in recent years to get rid of the comprehensive testing program, saying it has cost growers millions in produce recalls." (Isn't that the idea--to get tainted food off the market? Instead, industry suggests more private sector testing.
More private sector testing? Like the
third-party "audit" that missed the deadly listeria in the cantaloupe at Jensen's Farms? According to a
Congressional report on the matter released in January, FDA called it "an inherent conflict of interest" for a private auditor to provide safe handling advice in exchange for payment. Moreover, such auditors don't have to adhere to scientific standards, are not regulated by the FDA, and cannot enforce FDA rules.
This is also the same United Fresh Produce Association that
claims to care about food safety but
does not want to pay the fees necessary to fully implement the Food Safety Modernization Act, the new law intended to improve inspection and oversight by the Food and Drug Administration.
According to the
Center for Responsive Politics, the United Fresh Produce Association has spent more than a million dollars a year on lobbying in each of the past three years. Of course only some of that money was spent lobbying on food safety but the trade group must expect a good return on its investment.
For its part, USDA claims the program doesn't belong there but is better suited to FDA, raising once again, the challenges caused by our currently fragmented oversight system and lack of a single, effective food safety agency.
The Food Safety Modernization Act may help fix some of these problems, but we still have to find the funding. Obama's budget also
seeks a 17 percent increase for FDA, but almost all of the new money would come from industry fees, which again, industry is dead set against. Moreover, it's not at all clear that FDA will pick up the slack from USDA's testing of fresh produce.
In sum, Obama is proposing to cut a nominal food safety program that's working fine, while suggesting new funds come from fees that industry will fight. Of course, testing won't solve all problems either. Not with an industrialized food system that consistently externalizes costs in favor of profits. Maybe if we examined how massive consolidation of produce growers, processors, and distributors contributes to these nasty outbreaks in the first place, and considered better prevention through smaller-scale production models, we wouldn't have to haggle over this testing program. But meantime, can't we find somewhere else to cut $5 million that doesn't make our problems even worse?
-----------------------------
Michele Simon, a public health lawyer, recently joined the Center for Food Safety as a Policy Consultant, where she will help CFS expand into issues related to food safety and nutrition. This commentary was first posted Feb. 22, 2012 on the
Center for Food Safety website.
From Merlin to Harry Potter, English magic has a long tradition. But what does it say about today's culture?
English occultist, bohemian and author
Aleister Crowley defined magick as "the science and art of causing change to occur in conformity with will". Crowley's will was aided by the inheritance age 11 of a tidy fortune, and took him on a hedonistic ride through a life of sex, drugs and occult practice. Member of the Order of the Golden Dawn, founder of the mystery religion of Thelema, self declared spiritual master and Magus and, significantly, accomplished chess player, Crowley revelled in his notoriety as "the wickedest man alive". The Great Beast's polyamorous lifestyle would barely contend for such a title in today's more liberal and permissive world, and the philosophy of ordering your world in line with your will is one that seems entirely accepted in our individualist society.
The Book of English Magic by Philip Carr Gomm and Richard Heygate offers a thorough and illuminating history of magic and magicians in England. It reveals a 5,000-year tradition of English magic, stretching from Neolithic shamen and Anglo-Saxon "Wyrd Crafters" to modern Wiccans, New Age spiritualists and Neo-Pagan revivalists. Along the way it catalogues the remarkable interplay of fictional and historical figures who have influenced and shaped the history of English magic. The fictional wizards from Merlin to Harry Potter who have shaped our perceptions of magic. John Dee, mathematician, astrologer, occultist and consultant to Queen Elizabeth I, who like Crowley and other "practicing magicians" crafted a powerful fiction around the cult of their charismatic personality. And the writers and artists who have drawn on magic as inspiration for their creations or even, like WB Yeats, have been drawn in to the world of the occult.
Reading this secret history, ensconced in
Topping & Company bookshop of Bath, the kind of independent bookseller that will gladly bring an idle browser a cup of tea as he muses on the nature of magic, and a location that could easily have been pulled from the pages of
Susanna Clarke's Jonathan Strange and Mr Norrell, I was struck most by the rich history of magical English stories it catalogues. Also in Topping & Company could be found magical stories by
JRR Tolkien,
CS Lewis and of course the mighty
JK Rowling herself (you don't have to have multiple initials to write magical stories for children, but it helps . Regardless of how you view The Book of English Magic's more eccentric thoughts on the reality of magic, it reminds us that Englishness and the English cultural identity have been intertwined with magicians and magic throughout their history.
No writer today is more associated with Englishness and magic than
Neil Gaiman. Aleister Crowley makes a caricature appearance in the very first issue of The Sandman, as the magus Roderick Burgess, whose failed attempt to summon Death herself launched Gaiman's comic series. Throughout his career from The Books of Magic to American Gods and beyond, Gaiman has systematically reinvented the archetypal characters and symbols of magic in his stories. But he has yet to declare himself a practicing wizard, unlike his fellow comic writer Alan Moore, who recently detailed his worship of the snake deity Glycon in
an alternative Thought for the Day on Radio 4. Moore's most potent work of magical writing is the
From Hell comic series, which outlines a conspiracy theory of royal involvement in the Jack the Ripper murders, around which Moore explicates his complex ideas on the magical nature of reality, tackling masonic rituals and the architecture of Nicholas Hawksmoor along the way. And the pulp aesthetic of comics has also been a launching pad for one of magic's greatest advocates,
Scottish writer Grant Morrison who in series such as The Invisibles and The Filth has created a complex philosophy synthesising magic and post-modernism, along the way penning the now iconic essay on
Pop Magic.
Magic seems to live at the heart of English identity, as much today as millennia ago if the hordes reading Harry Potter are any indication. But even if we assume, as most rational Guardian-reading folk no doubt will, that magic is nothing but hokum, poppycock and superstition, it's interesting to ask why it has such a profound hold over our popular imagination. Perhaps Crowley, magus and chess master, provides a possible answer. As any good player knows, the strategies of chess are as relevant in the real world as on the playing board, and many a politician has studied that game to understand the larger games of politics and power.
Perhaps magic is another kind of game, where the symbols and theatricality of the occult mask metaphors for power to help us understand the "science and art of causing change to occur in conformity with will". No wonder we English, living with the lingering ghosts of Empire, an unreformed class system, and the complexities of a post-industrial economy, find such fascination in it
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We Love Pharma, courtesy of CDM Worldwide
The pharmaceutical industry gets a bad rap. To listen to the critics you’d think pharmaceutical companies are in the same sleazy category as oil, finance and tobacco companies. But pharmaceutical companies invent life-saving medications, not to mention countless other psychoactive products that many of us enjoy on a recreational basis. Pharmaceutical companies get blamed for fraud, kickbacks, and research deaths, but they never get the credit for oxycontin.
That is why I was thrilled to see that GlaxoSmithKline is sponsoring the prize for the
British Medical Journal
‘s annual
Research Paper of the Year. Sure, the pharma-bashers will whine like infants at the
BMJ’
s decision to brand a medical research prize with the name of multinational drug company, just as they’re whining about an American editor’s decision to re-locate a leading bioethics journal to the Texas headquarters of a
stem cell tourism clinic. These people just don’t get it. This is not about propaganda or corruption. It is about developing innovative medications for diseases that we didn’t even know existed.
In that spirit, my nomination for the GlaxoSmithKline (GSK Research Paper of the Year goes to a ground-breaking article about GSK’s very own antidepressant, Paxil, which was published in the
Journal of the American Academy of Child and Adolescent Psychiatry
. The title of the article is “Efficacy of Paroxetine in the Treatment of Adolescent Major Depression,” but seasoned pharma-watchers know it better as
Study 329. The data behind Study 329 showed that Paxil didn’t actually work in adolescents – that, in fact, it was
no better than a sugar pill. However, as any marketer understands, bad data cannot be allowed to interfere with a good paper. By the time Study 329 appeared in print, GSK had used the magic of biostatistics to transform the raw data into a gleaming advertisement for Paxil. As a result, when FDA eventually decided that Paxil had a few minor side-effects,
such as suicide, Study 329 had already done its work: getting a GSK product into the hands of troubled teenagers. And wait, here’s the beauty part: although the published version of Study 329 was “authored” by leading academic psychiatrists, it was actually
written by a GSK ghostwriter.
Of course, the pharma-bashers have been complaining about Study 329 for years. Some of them even want the journal to retract it. The lead “author” who signed the paper, Martin Keller of Brown University, has been
beaten up by the Senate Finance Committee,
harassed by the New York attorney general, and vilified in the press, all because he put his name on a ghosted article and forgot to report
half a million dollars in pharmaceutical income. To which I say: stand strong, GSK. Ignore the naysayers and the nitpickers. It’s about time you gave these good people some public recognition. Yes, it’s true that Study 329 is eleven years old, but you’re paying the BMJ over $47,000 to
sponsor this prize. Surely they can bend the rules, just this once.
Dr Andrew Farb, a medical officer at the U.S. Food and Drug Administration (FDA has advised clinicians on live case demonstrations of devices.
A study in the Journal of the American College of Cardiology: Cardiovascular Interventions suggests that broadcasting heart procedures live to doctors at medical meetings may not present a risk to the patient on the table. Doctors at Rambam Medical Center in Haifa, Israel reviewed 101 patients treated during live transmissions from a single center in 15 invasive-cardiology conferences between 1998 and 2010. The study found that procedural and 30-day clinical outcomes were similar to those found in daily practice and to those that have been reported in the contemporary published data, and concludes that these results suggest that broadcasting live case demonstrations in selected patients from selected centers may be safe.
Such demonstrations must first be approved by the FDA. In an interview with Reuters Health, Dr Andrew Farb, who co-wrote an editorial published with the findings said the main goal of these demonstrations is to increase awareness of a clinical trial, and possibly get more doctors to enroll patients in it. This, he stated, is part of the FDA's "mission" to help get clinical trials done in a timely manner and get effective treatments into practice.
Dr Farb also noted that the demonstrations must clearly state that the procedure involves an "investigational device," and the operators cannot try to commercially promote the device.
The full article from the Journal of the American College of Cardiology can be found
here.
Read the Reuters Health interview with Dr Andrew Farb
here.
Watch the Video ]Engineers at the Stanford University School of Engineering have for the first time demonstrated a wirelessly powered medical device so small that it can be implanted in the human body and propel itself through the bloodstream, a feat scientists have been trying to accomplish for more than fifty years. Ada Poon, an assistant professor at Stanford, and lead researcher of the project, presented her research at the International Solid-State Circuits Conference (ISSCC in San Francisco. She demonstrated to members of the conference how the device can be implanted or injected into the human body where it can be powered wirelessly using electromagnetic radio waves instead of batteries or power cords. “Such devices could revolutionize medical technology,” said Poon. “Applications include everything from diagnostics to minimally invasive surgeries.” She said these medical devices could travel through the body delivering drugs to where they need to go, performing analyses, and even zapping blood clots or removing plaque from sclerotic arteries. These tiny wireless devices could one day replace most of today’s implements that are run on large, heavy batteries that must be changed periodically. And most of the current devices in use have batteries that take up half the volume of the device. “While we have gotten very good at shrinking electronic and mechanical components of implants, energy storage has lagged in the move to miniaturize,” said co-author Teresa Meng, a professor of electrical engineering and of computer science at Stanford. “This hinders us in where we can place implants within the body, but also creates the risk of corrosion or broken wires, not to mention replacing aging batteries.” The wireless devices are much different. A radio transmitter sending signals to the device would remain outside the body. The device picks up the signals using a tiny coiled wire antenna. The two are magnetically coupled such that any change in current flow in the transmitter induces a voltage in the antenna. The power can both run the device and propel it. Although its sounds like an easy task to accomplish, Poon said it was anything but. She first had to upend some long-held assumptions about the delivery of wireless power inside the human body. According to scientific models, high-frequency radio waves dissipate quickly in human tissue, fading exponentially the deeper they travel. But on the other hand, low-frequency signals penetrate easier. However, these require larger antennas -- a few centimeters in diameter -- to generate enough power for the device, far too large to fit through most arteries in the body. So, based on the models telling engineers that it could not be done, they never tried. But then, engineers, namely Poon, looked at the models more closely and realized that scientists were approaching the problem incorrectly. They assumed that human muscle, fat and bone were generally good conductors of electricity, and therefore governed by a specific subset of the mathematical principles known as Maxwell’s equations -- the “quasi-static approximation” to be exact. Poon, taking a different approach, chose to model tissue as a dielectric -- a type of insulator. As it turned out, human tissue is a poor conductor of electricity. But, radio waves can still penetrate through them. In a dielectric, the signal is conveyed as waves of shifting polarization of atoms within cells. She also discovered that human tissue is a “low-loss” dielectric -- meaning little of the signal gets lost along the way. Using the new models, she recalculated and made a surprising find: Using new equations she learned high-frequency radio waves travel much farther in human tissue than originally thought. “When we extended things to higher frequencies using a simple model of tissue we realized that the optimal frequency for wireless powering is actually around one gigahertz, about 100 times higher than previously thought,” said Poon. And more significantly, the antenna inside the body could be 100 times smaller and induce the same amount of power. The antenna Poon demonstrated was just two millimeters square; small enough to travel through the bloodstream. Poon developed two types of self-propelled devices. One drives electrical current directly through the fluid to create a directional force that pushes the device forward, moving at about a half-centimeter per second. The other type switches current back and forth in a wire loop to produce swishing motion similar to the motion of a kayaker paddling upstream. “There is considerable room for improvement and much work remains before these devices are ready for medical applications,” said Poon. “But for the first time in decades the possibility seems closer than ever.” Poon’s research was supported and funded by C2S2 Focus Center, Olympus Corporation, and Taiwan Semiconductor Manufacturing Company. --- On the Net:
