Cancer Patients Try Experimental Meds In The UK
8 CommentsBy Ed Silverman // April 18th, 2008 // 6:45 am
When Jill Bracey Cowley was diagnosed with bone marrow cancer eight years ago, doctors told her she had two years to live. So she decided to take a gamble and try new drugs that hadn’t yet been approved. “They’ve utterly changed my life,” says Cowley, 70, who credits the treatments with enabling her to live long enough to welcome six grandchildren into the world, according to the Associated Press.
Unlike most terminally ill patients, Cowley had the chance to try untested drugs. With the opening of a government-run network of experimental clinics this month, UK docs hope to offer millions of dying cancer patients the same chance. The network builds on cancer research centers established in 2002 to bring advances quickly to patients. Each center will receive $4 million to develop new treatments. Under government-supported trials, Cowley has tried at least four experimental meds for free. Her doctors aren’t sure which ones have had the most impact but say her situation is stable.
In the US, cancer patients can also sign up for experimental treatment, but the AP points out there is no official national effort to help patients enroll. Most trials are run in academic centers, while 80 percent of patients are treated in community hospitals. The American Cancer Society offers a matching service to line up suitable experimental trials for cancer patients, but success rates vary. There is also a government-run web site that provides trial listings for all diseases. According to a 2005 report, 20 percent of US patients are eligible to participate, but only about 3 percent enroll.
The UK has 19 centers where terminally ill patients can apply to try untested drugs. While clinics in France, the Netherlands and Italy offer cancer patients experimental treatments, no other European country has such a national network.
It is rare for patients with late-stage cancer to have opportunities to try experimental drugs, and experts estimate only hundreds in the UK currently have access. But with more centers open, officials hope thousands will soon benefit. The government initiative also aims to speed up the drug testing process. Some experts estimate there are 500 potential new drugs in the pipeline, many stuck in the research phase as scientists recruit human volunteers, the AP writes.
Getting new cancer drugs usually takes a decade, from the time they are developed in the lab to the time they are licensed for patient use. “We want to cut that time line in half,” John Gribben, professor of experimental cancer medicines at the St. Bartholomew’s and London hospital, tells the AP. The clinics will run early trials of drugs that have never been tried in humans before. Docs will have to monitor patients closely to watch for dangerous side effects. “We will take regular samples from patients to quickly assess whether or not the drugs are doing what we want them to do,” Gribben says.
One of the biggest challenges is guessing what the appropriate dose might be. “The only way to know the right dose, to work out how toxic a drug is and if it’s hitting a target, is for someone to try it,” Karol Sikora, a cancer expert at Imperial College School of Medicine at Hammersmith Hospital, London, tells the AP. “The risk is usually small, but there’s always some risk involved.”
Docs usually start with a very low dose and gradually increase it until the drug is working or patients can’t tolerate it. But things can still go wrong. In 2006, six previously healthy volunteers developed convulsions, suffered organ failure and lapsed into comas hours after being injected with a drug intended to treat leukemia and autoimmune diseases at Northwick Park Hospital in London. One man has since been diagnosed with cancer.
The AP adds that critics say expanding drug tests for terminal cancer patients preys on the desperation of dying people. But some ethicists say that as long as patients are told about potential side effects, the process is fair. “How can you lower the bar too much for people who are going to die anyway and for whom this is a last hope?” John Harris, a professor of bioethics at the University of Manchester, tells the AP. “We’re offering them a chance when they have nothing to lose.”
Still, it is a very slim chance. Early trials are only designed to test if drugs are safe, not whether they actually work. “There’s only a 5 percent chance that patients will get any benefit,” Franco Cavalli, a cancer expert with the European Cancer Organization, tells the AP.
In the UK, several agencies monitor the safety of experimental cancer tests, including the Medicines and Healthcare products Regulatory Agency and the European Medicines Agency. In the US, all study designs must be approved by the FDA before trials can start. To safeguard patient safety, the trial must also have the consent of an independent group of experts. The Office of Human Research Protections, a government agency, also works to protect people involved in federally-funded research.
For patients like Cowley, for whom standard cancer treatments have failed, experimental drugs are the only option. “It never occurs to me that I’m a guinea pig,” she tells the AP. “I know the doctors need to test the drugs to find out if they work or not, but for me, I just want to carry on living.”
Source: The Associated Press
Nathan
Ed,
Maybe I should read the AP article — but I’m a little confused. Are we talking about drugs in Phase I, Phase II, or Phase III? It seems as if they are talking about Phase I. If that’s the case, I don’t see a lot of point in this exercise because Phase I trials are usually conducted in healthy volunteers — the dose is only escalated briefly to look for side effects, probably not long enough to see a therapeutic effect.
Also, I’m confused by this statement: “Under government-supported trials, Cowley has tried at least four experimental meds for free. Her doctors aren’t sure which ones have had the most impact but say her situation is stable.” Aren’t these controlled clinical trials? Or is this just some doctors giving experimental medicines to patients who are not part of clinical trials? It’s hard to imagine a drug company allowing enrollment in 4 cancer clinical trials. As the statement above points out, it would be nearly impossible to tell which drug had an effect. The experimental treatments may have helped this woman — but they did no good for all the other cancer patients out there waiting for new treatments. The point of clinical trials is not to help the individual — it’s to see if the drug can help the larger population. In this woman’s case, that didn’t seem to happen.
Ed Silverman
Hi Nathan,
I linked to the AP story because I’m not in the UK to report this myself and it’s an interesting development. Two, I’m not sure that you will find the answers to all your questions. I’m afraid the story doesn’t say which specific phase of development. And so I understand your frustration, because that’s a good question. Nonetheless, one point the story makes is a contrast between the UK and US systems. Access to experimental meds is an issue here.
Regards
ed
Jack2
My understanding is that in the US, Phase 1 cancer studies are not done in healthy volunteers - because of the high toxicity risk of these drugs. In the US industry does not test them in healthy volunteers, ever, at any phase.
I don’t know why this study mentions healthy volunteers. Perhaps its a UK/US difference or an academia/industry difference.
RTW
Jack2. You are correct. In general most anti-cancer drugs are tested in phase I cancer patents usually expressing the type of cancer the drug is meant to treat, although sometimes they will admit other cancer patents in trials aimed at discovering synergies between drugs in combination for example.
There has been a lot of talk in doing double blind studies and studies in healthy volunteers but the ethics of such a process are less than optimal when dealing with something that can be as toxic to normal tissue sometimes as cancerous tissues. This is changing as we better understand cell signaling and seek to use non toxic drugs to control or manage cancer more in lines with how diabetes is managed.
Dan
From a logical paradigm, if a candidate for an experimental med is likely to die soon, should they not explore all possible methods of treatment?
Nathan
Dan,
That makes since for the individual. However, experimental drugs are not on the open market yet. The FDA approves an IND for a particular investigation. Treatment of patients with the experimental drug is NOT for the good of the patient. The purpose of the treatment is to test a hypothesis and to establish the efficacy and safety of a potential new drug. Uses that don’t fit into this role should not be allowed (in my opinion).
Their only use should be for experimental treatment. If one cannot discern the results of experimental treatment (which one of these 5 drugs actually helped?), then the “experiment” was a failure. This is similar to the issue explored by the supreme court back in January. Link below:
http://www.pharmalot.com/2008/01/us-supreme-court-no-review-of-experimental-meds/
Former pharma Marketing Exec
All,
As reported, cancer drugs are used on real patients in phase one in the US who have no other alternative. Nathan is right, it isn’t for the good of the patient, but the patient may derive some benefit. However, the problem is that Phase one is dose escalation trial (in cancer) and the problem is that the patient might develop resistance before they derive a benefit at all.
I am not sure why the patient mentioned was allowed to be in 4 trials somewhat simultaneously, not very good planning.
But depending on the drugs studied there could be some delayed benefits that is causing the problem. Usually the time lapse between trials is about 6 weeks for a “washout” period.
For the record, we should look at this as a potential solution to the problem we have here with regards to the issues of the Abigail Alliance as I posted on another thread http://www.abigail-alliance.org/
Thanks for both of these Ed.
Mark
I’d like to clarify a few things about clinical trials for oncology agents. For cytotoxic drugs, clinical trails are conducted in patients. However, for drugs such as the RTK inhibitors, some clinical trials are conducted in healthy volunteers. These trials would be mainly conducted in order to understand the PK of the drug in a human population in which disease of concomitant medications would not have an impact on the PK of the drug. For example, the first clinical trial with sunitinib was conducted in healthy volunteers. Nine subjects were administered a 50 mg dose. Studies to assess the effect of food, ketoconazole or rifampin on the PK of sunitinib were also conducted in healthy subjects (15, 27 and 28, respectively). The SBA for Sutent shows at least 8 trials enrolling 117 healthy subjects. Healthy volunteer studies were also conducted for sorafenib, lapatinib and imatinib.
Also, the initial clinical trial is often conducted in “all comers” unless there is a clear scientific rationale as to why the drug would work in a specific cancer only. An example of a drug using this approach was Velcade.