Woman’s cancer killed by measles virus in trial
washingtonpost.com
washingtonpost.com
The paper presents 2 cases, selected because they were the first 2 cases to be tested at maximum viral load. There are additional people in the trial, and they will release full results once they are available.
It included two slides showing before/after blood levels and imaging. They talk about how they modified the virus to emit a tracking signal, and how they modified it to target the cancer cells. Really, really mind blowing and impressive work. I would love a tour of that lab.
These are end-stage patients for whom everything else has stopped working. One of the patients had already undergone several experimental treatments. There is some really exciting research going on for MM (multiple myeloma) treatments, and maybe even cures.
I think this is one example of the free market working well. Typical MM treatment runs about $60k / year, and with recent developments, patients are living 10+ years. Total number of MM patients is increasing both because the disease is becoming more prevalent, but mostly because people are living so much longer with MM. In short, it's a large and growing market. But it's not a cancer you can treat and have it go into remission. You get on treatment, and you stay on it and keep those levels down. The typical treatment is biweekly therapy.
But these OVs are one-time deals. So a single dose treatment is a very interesting alternative. The only problem is, MM is extremely resilient, and the cells are everywhere. It's so hard to eradicate, unless the OV is a cure, it's just another tool in the box to manage MM and extend lives.
Weird, the PDF of the actual paper was freely downloadable a couple hours ago, but now it seems the paywall is up? http://www.sciencedirect.com/science/article/pii/S0025619614...
Yes, the key point to watch next is to see if the MM does not come back after a couple of years.
I think the curative approach will ultimately come from immunotherapy, training the body to attack the cells. OV could certainly have it's place, for example as an alternative to ASCT.
As i know, just killing the cancer cells is not enough. The real curative treatment is to kill cancer stem cells using drugs.
http://www.survivingmesothelioma.com/news/view.asp?ID=001532
EDIT, addendum: If you have a few treatments that each can kill 9999/10000 cancer cells. It seems the current approach is apply treatment a. Not detectable yay! They grow back to original numbers. Apply treatment b! etc. If you did them all at once, they wouldn't have time to grow back in-between treatments giving a larger chance you get them all.
At some point the risks of the treatments outweigh the risks of leaving some cells.
http://www.cancer.org/cancer/breastcancer/detailedguide/brea...
That's general audience information that discusses treatments before and after surgery that are intended to work along with the surgery. If you click through to the various therapies, there is lots of discussion of combining them.
Source: video/source article at http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...
Edit: Accompanying editorial to go along with the paper and video: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...
They mentioned the second patient in the article:
The trial included two patients. Russell said the treatment worked in Erholtz, whose tumors were mostly in her bone marrow. However, it was unsuccessful in the other patient, whose tumors were mainly in her leg muscles, the Star-Tribune reported. He said more research is needed to know how the nature of the tumor affects the virus.
http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...
Editorial Article: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...
We started with Lenalidomide and was on it until end of last year with breaks of up to 6-8 months where there was no specific meds.. He's now on a Bortezomib cycle which will end in a couple of months and we hope to have some months free of meds again..
We never did the bone marrow transplant considering his age and stress/recovery he would have to go through.. MM is sympathetic in the sense that people who respond to meds can have a high quality of life even while undergoing treatment (my dad is still a practising medical Doctor). Lenalidomide is a tablet that you take at home while you go in once every week or two for Bortezomib shots.. The treatment is also considerably cheaper in India (still not inexpensive by any measure)..
The overarching fear for MM patients is the fact that its indeed incurable and how far/long we can go on before running out of treatment options.. Personally, seeing such trials and success gives us hope and comfort.. OV looks a promising approach and I hope my dad and others will be able to benefit from it..
If coming to the US is an option, there is a treatment center (Myeloma Institute for Research and Therapy MIRT) that is part of the University of Arkansas and is probably one of the best places in the world to get myeloma treatment. I know quite a number of people that have gone there and gotten good results.
It is based in Little Rock (of all unlikely places) I think because it was founded by a grant from Sam Walton, founder of WalMart. He died from MM in 1992.
How so? While I'm sure the Mayo Clinic will be attempting to patent and license this therapy, the research was apparently funded by the US government and various philanthropies.
[Quoting relevant sections of the paper since the full text is paywalled.]
"Grant Support: This work was supported by funds from the National Institutes of Health/National Cancer Institute (grants R01CA125614 and R01CA168719), Al and Mary Agnes McQuinn, the Harold W. Siebens Foundation, and the Richard M. Schulze Family Foundation. The National Cancer Institute RAID (Rapid Access to Intervention Development) Program supported MV-NIS manufacture and toxicology/pharmacology studies.
Potential Competing Interests: Drs Russell, Federspiel, and Peng and Mayo Clinic have a financial interest in the technology used in this research."
If public funds and private donations could actually cover the research costs getting all the way to FDA approval, I would think you would see more doctors and researchers creating nonprofit partnerships to attract the funds and do the research. Sounds like it would be a dream come true to be funded to do research you cared about and better the lives of millions without the corporate suits getting in your way. But I think the reality is the facilities alone cost hundreds of millions if not billions, so just for Mayo to give you the lab space to work for a couple years is a major investment.
I don't know why we go through this kabuki process of pretending there is a functioning market in places where the government is such a dominant player (see also defense contractors). Why not just cut out the middleman?
At this point I risk conflating not just two but three arms of the government: the NIH (funding), FDA (approval), and Medicare (payment).
> Why not just cut out the middleman?
Medicare has hinted at doing this, using its purchasing power to drive down the cost of drugs and refusing to pay for treatments approved to work but who have a low cost-to-efficacy ratio. A recent example is the fight over Hepatitis C medication[0]
[0] http://www.npr.org/blogs/health/2014/05/12/307747798/boomers...
Is Walmart paying for the QA testing?
The government pays for the early research, sets all the ground rules for the drug trials, and -- as the drug companies' biggest customer -- ends up ultimately shouldering much of the cost of those trials whether successful or not. The government certainly has the financial wherewithal to fund stage 3 trials, $100M a pop is a rounding error on federal spending or even on just federal medical spending. So why not just go ahead and do so? Why the farce with pretending there's a healthy drug market when the government is driving so much of the process? Let's just admit this is a market failure of the public good variety, like firefighting and roads, and have the government provision it.
Slightly tangential, but I wonder where the IP in this discovery is? If there is nothing to sell but injecting cancer patients with standard lab-grade measles, I think it is particularly open to being copied. Granted the measles used is genetically tweaked, but nothing I believe to enhance the therapeutic effectiveness.
Well Fleming (who discovered antibiotics) was working for the (British) government, so if the above is in any way an indication of "the free market working well", then his extremely more important results were an example of public sponsored research working great.
I think all this investment has been bolstered by the market success that Revlimid and Velcade are seeing. These drugs are cheap to produce, sell for about $5k per weekly or biweekly dose, and that a large and growing number of people are very happy to pay for, because they are well tolerated for as long as they work. Revlimid is just a pill you take, Velcade is a shot in the arm, so both are very cheap to administer.
There is huge incentive to keep producing more of these MM treatments, because the MM becomes refractory to each successive therapy over time. If you can make a good first-line treatment which is effective for 3 years on average, that's more than $100k per patient, at what, 90% gross margin?
I don't mean "free market" in the libertarian sense. I mean it in the sense that investment capital follows investment opportunity, and we are definitely seeing that here.
Is there any likelihood that measles, or a similar virus we have held at bay with vaccination, was actively fighting cancer 200 years ago, thus pushing up the incident rates that apparently have gone up and dismissed with "well we weren't dying of cancer because we were dying of $INSERT_DISEASE_HERE"
Rolling out vaccination is a Good Thing.
cheers
For this to be the case, cancer must have been killing a significant number of people before they reached the reproductive age. However, we know cancer rears it's face well passed people have reached reproductive age. For women, breast cancer the most common of them all becomes rampant post-menopause.
With this view point, it seems unlikely that measles was an evolved response to cancer. Because, this has been a hand waving argument it has not addressed the ratios required for an evolutionary response, i.e Is it possible that cancer was killing enough (however small) prepubescents and that gave measles a chance to evolve?
Or, could it be that there was a way milder measles like virus that people acquired (like the common cold virus) and lived with henceforth and that protected them from cancer?
There are many interesting questions that come up.
I'm not saying this is likely, I'm just pointing out that your restatement of the question is a lot more narrow than the original question.
It is even possible that different viruses could be fighting each other to get a piece of our cancer. Interesting stuff!
Thanks
Evolutionary forces are still in play for people past their reproductive age, though admittedly in a much less direct way. A person that lives long enough to help care for their grandchildren will be more likely to have some of their genes survive.
Looking at it another way, if old people weren't useful evolution would not have produced humans with such long lifespans after reproductive age (since the old people are consuming resources, populations where individuals died off shortly after the kids were autonomous would have had an advantage).
There is some research along similar lines regarding exposure to certain parasites and disease.
http://www.scientificamerican.com/article/helminthic-therapy...
http://www.bbc.com/future/story/20130422-feeling-ill-swallow...
It is however mathematically certain that the prevention of deaths from infectious diseases will drive up rates of death from other causes, as we have to die of something - the only question is what.
It seems to me that a very high percentage of people would opt for a potentially fatal, completely untested course of action as opposed to imminent death. So who gets to try these treatments, who tells dying patients they are not allowed them, and is there a black market or large amounts of money changing hands for experimental procedures?
Ekianjo in this thread quoted 7 years at the earliest for a treatment to become available. Surely with hundreds of thousands of desperate, dying, last chance sufferers, it is better to go to extreme measures and offer the most promising yet dangerous treatments to everyone. Is it simply a side effect of the way pharmaceutical companies have to do business? If so, it's sad, and maybe a larger share of cancer research money should be put towards 'out there' attempts to cure terminal patients.
Genuinely curious.
It's also worth noting that there is a constant sussurus of "miracle cure for foo!" that doesn't actually pan out in the long run.
One could argue, how could the trials NOT be morally randomised? Are we doing a disservice by not conducting the trials in a way to study the efficacy of certain drugs.
PS: Wit is a great movie that deals with terminal illness from the patents perspective. If I recall correctly there is a vary minor subplot around a trial on the proper drug dosage. At no point is the idea that this might be a cure just possibility of slightly extending your lifespan at the cost of a lot of pain. It's basic cost/benifit analysis but taking higher doses is in no way presented as better.
> a very high percentage of people would opt for a potentially fatal, completely untested course of action as opposed to imminent death. So who gets to try these treatments, who tells dying patients they are not allowed them, and is there a black market or large amounts of money changing hands for experimental procedures?
First, for many cancers you do not die of an imminent death. Sometimes it can take 5 to 10 years to die from Cancer.Unless you are affected by a cancer where no treatent is available, there are usually multiple courses of treatments you can follow before being out of options.So patients are actually trying existing methods before jumping to new treatments. New treatments are only available in small quantities and there are strict criteria for the selection of patients. And in Oncology actually we already give the chance for patients to try new drugs as soon as the safety evaluation begins, whereas for other therapies we go through healthy volunteers first. For a patient there is not much incentive to join Ph1 since the efficacy is not proven and there is a dose escalation method so you may not get the efficacy dose even if you enter the trial. Besides, there are safety risks involved and some patients die in Ph1. So every patient signs an informed consent that they are aware of the risks involved.
As for the hundred of thousands of patients, the companies cannot support them for many reasons: as mentioned, the drugs are only manufactured in small quantities in early stages and it takes years to scale up the process. Second, clinical trials cost a lot of money, and the more you have patients the more it costs. So you dont recruit more patients than what you need to do your evaluation. This being said, most pharma companies continue providing drug even after the trial is completed to patients who see efficacy with it. Third, the larger the trial, the longer the enrollment time and the longer it takes to get the results back and therefore the longer it takes before the drugs reach the market.
As for offering this to desperate, last chance sufferers, unfortunately the history of potentially revolutionary cancer treatments shows this is a bad idea. If the treatment kills 90% of people within hours or days of treatment (sadly this is a realistic outcome before dosing is worked out and in some cases, regardless) then it is morally unacceptable to roll it out to thousands of people. You have to do the trials first to establish whether it works, is safe, that it doesn't cause unnecessary suffering and hasten death and what the optimal dose and protocol is. You also have to figure out how to deal with patients who do have an adverse reaction to the treatment.
The FDA regulates every aspect of clinical trial design. Dying cancer patients are always the first to receive untested drugs -- the FDA has set the bar that any new therapy must outperform what is currently used. There is no "black market" for experimental procedures, mostly because you must visit a hospital to receive them in the first place. Some drugs are intravenous; all are given with standard oncology examination. A doctor cannot write a prescription for a drug not on the market yet for you to pick up at the pharmacy!
> Surely with hundreds of thousands of desperate, dying, last chance sufferers, it is better to go to extreme measures and offer the most promising yet dangerous treatments to everyone. Is it simply a side effect of the way pharmaceutical companies have to do business?
In order for the testing of a Phase I trial to be complete, patients must meet certain criteria. The FDA (and, by extension, the pharmaceutical companies who want FDA approval) require enrolled patients in a clinical trial to have similar levels of disease. A patient that is clearly near end of life may not be able to physically swallow a pill...their outcome may bias the trial's results.
Yes, there are desperate and dying cancer patients, but a Phase I trial can (and should!) only accommodate dozens of them to achieve proper statistical power. Phase II may take hundreds, and Phase III will take even more -- but when a drug is approved, it has the possibility of being given to many thousands or millions of patients all at once.
As the trial population grows, medicine rears its stochastic side -- despite patients having pathologically similar disease, some will be helped and others will not. This is at the core of all FDA trial design: big populations are necessary to see just how effective your drug is. It should not be surprising, then, that the majority of failures happen at the bigger scales (PhII and PhIII).
The original studies of aspirin and heart disease were, for example, halted because the benefits were so clear that it wasn't considered ethical to keep the placebo arm untreated.
Several HIV trials have similarly been halted because the treatment was showing no or negative effects.
From my completely uninformed point of view it seems that if it's real, it changes everything...
The first patient did have a recurrence of a single tumor that was treated locally, with her marrow remaining completely clear. The second patient had his marrow cleared and all but a couple tumors in his legs resolved. And the virus penetrated those tumors and allowed full 3D mapping of them due to tags attached to the virus itself (it sounded like a thyroid produced chemical was attached to the virus as a tag). The implication was that because of the detailed mapping that it would be possible to resolve/remove the remaining tumors in the leg muscles of the second patient.
So, the answer is quite a bit much more complex than 50%. Both patients cleared the myeloma from their marrow. Almost all (numerous!) tumors were removed, from a single treatment in each patient.
Edit: Here's a link to the editorial article that accompanies the paper: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...
"Within the next several years, it is likely the technique will become a standardized treatment for cancers such as myeloma or pancreatic cancer, Tanios Bekaii-Saab, a researcher at James Cancer Hospital and Solove Research Institute in Ohio, told the Star Tribune. Still, the study must be confirmed in large randomized clinical trials. “Unless we get to the third stage of development, we are cautiously optimistic,” he said."
Source of source: http://www.mayoclinicproceedings.org/pb/assets/raw/Health%20...
More on reddit/science: http://www.reddit.com/r/science/comments/25j3je/mayo_clinic_...
Even if they get to Ph3, cancer trials usually take several years to enroll and to reach results, and it wouldn't be a therapy before 6-7 years down the road at the earliest, since you'd want to demonstrate PFS and OS improvement and that takes time in certain forms of Cancer.
EDIT: Patients experiencing complete remission is not completely exceptional in Phase Is. it happens, but it's usually very rare that it occurs in MANY patients. So, effectively speaking, this is n=1 datapoint at this stage, unless demonstrated otherwise.
Perhaps. Or perhaps not. It depends. If it shows to be safer than a bone marrow transplant (insanely dangerous) its got potential.
It's all a benefits/risk analysis.
http://www.forbes.com/sites/matthewherper/2014/05/07/is-this...
More like: it's the problem that every effective cancer therapy solves in some (so far always limited) way.
The earliest case reports I remember date back to the 1600s and for a short time in the late 19th early 20th century there were doctors that practiced that way however the results seemed highly variable and generally fell by the wayside.
It is great to think that this might be true, there is certainly evidence to suggest it is somewhat credible but like anything we will require more evidence before we can claim that it 'changes everything'. We can always hope though.
- ps apologies for lack of sources, I'm on mobile, I'm a doctor working on an oncology ward and I just had my worst day in my 5 month long career today and hardly in the mood to do the research legwork required to substantiate my claims. Google will help - start with hyperthermia therapy if interested in going down the rabbithole
Thee is actually a really interesting paper, tangentially related, on sepsis (blood borne infections) which randomised ICU patients to have either aggressive temperature management (ie fans, active cooling and paracetamol) vs allowing the temperature to rise as high as 39.9. Although the study was small in size(I think there were roughly 15 in each arm) the 'permitted fever' arm had only 2-3 fatalities vs 14 in the aggressive fever management arm. I actually have that paper on my desktop and will dig it up
The video that's included with the full text explains the study in layman's terms and is very accessible to the general public. Lots of good info there.
Edit: Here's a link to the editorial article that goes along with the original paper and video: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...
Dad of a child who died from cancer and well the word cancer doesn't mean squat you need to know what type of cancer. Is it sarcoma or what? http://www.cancer.gov/cancertopics/types/commoncancers
It’s not very useful to know only that you have a disease that is caused by a virus. It could be a common flu, melease, ebola, herpes, hepatitis, hiv, ... http://es.wikipedia.org/wiki/Virus#mediaviewer/Archivo:Viral.... Each one has a very different treatment and prognosis.
Some cancer would kill you in a month and some will kill you in 100 years (if you don’t die from other cause), some cancers are easy to operate, some are easy targets to chemotherapy, some for hormone therapy, some for radiation, ... A cancer diagnosis is a bad new, but it’s a very wide range of bad.
Also a new “cure” will probably be useful in a very few specific cases, and not useful in a general case like a broad spectrum antibiotic, that is useful against a lot of kind of bacteria.
Such is not the case with cancer. Prognosis is the main differentiator, but that's not enough to say "stop using cancer as a catch-all."
It's a wide classification that still tells you what is happening inside the body, which is not the case with a bacterial or viral infection.
But want to say that after a period where the definition of cancer broadened out to a multitude of diseases as you say, with the help of genetics I think it's starting to converge back - many different cancers work through similar genetic mechanisms. We're slowly starting to understand common themes that act broadly across many cancers. With the help of recent advances in sequencing people are finally getting a grip on tumor heterogeneity (something that was previously misunderstood) and it seems like across many cancers, we are starting to get a feel for how cancer responds in common ways to drug interventions, and why it can be so resilient and difficult to eradicate. So yes, lots of diseases, but underlying it all, there's a common genetic architecture.
http://www.marketwatch.com/story/amgen-provides-update-on-ph...
http://en.wikipedia.org/wiki/Talimogene_laherparepvec
Not, it would seem, a panacea. Approach is interesting in that aspects of cancer biology make the cells more vulnerable to viral infection, eg supressed interferon production. Also a possible platform for immunotherapy ie getting the immune system to attack a virally infected cancer cell might wake up a more generalised immune response. But, medical grade virus is expensive to produce, and hard to think how a viral infection could eradicate 100% of the billions of cancer cells present in advanced disease. Also, humans get immune to viruses after infection.
From the paper: "Unlike naturally occurring measles, MV-Edm, and hence MV-NIS, targets CD46 as a cell-entry and cell fusion receptor. CD46 is a ubiquitous complement regulatory protein that, fortuitously, is highly expressed on human myeloma cells, making them abnormally susceptible to MV-NIS infection, syncytium formation, and cell killing."
So they tweaked the virus to target CD46 which MM cells express way above normal. The MM cells are therefore significantly more susceptible to being killed by the virus.
I might add there's no such thing as "cancer", cancer is caused by numerous kind of mutations (from various origins, including viral infections) and there's no single bullet against cancer. There are already many good treatments for several types of Cancer but not all, and cancers discovered late have usually bad prognosis no matter what. This being said there are exciting new treatments coming in the 2010s using antibodies instead of regular chemotherapy, which may improve survival for many patients.
Doesn't that mean there is such a thing as cancer? Perhaps the final cure would be an augmented immune system that can tunnel to any area of the body and remove these cells. Something like nanobots I guess.
Although I do understand your point, that the several hundred forms of cancer in humans require radically different approaches for curing until nanobots.
That's just the impression I get from the article. I know literally nothing about this do if anyone with actual knowledge can explain properly please do!
The article also mentions that most people in US are vaccinated—I'm not sure how to read that: vaccinated from this particular virus?
What are the long-term risks if we start injecting people with large quantities of a virus to battle another decease? Could that virus evolve into something much worse than cancer?
I would hope that quarantine procedures around any human made-or-modified virus would be quite strict to avoid something unwanted making it's out of the lab.
Can't they circumvent this by injecting more of the virus than the body can fight at once? Though it's starting to sound like regular expressions...
From the link mentioned in "According the clinic’s statement released Wednesday" line.
It would be really great if this turns out to be a real treatment option because, harsh as it appears from the article, this woman's treatment sounds way easier than the current therapies for myeloma.
If you mean the cancers becoming resistant, one of the appeals of using viruses in therapeutic settings is they can evolve right alongside their targets, helping mitigate some of those resistance problems.
http://www.bcmj.org/bc-centre-disease-control/heavy-metal-po...