News Nature 446, 474-475 (29 March 2007) | doi:10.1038/446474a;

Published online 28 March 2007

Cancer patients opt for unapproved drug
Helen Pearson

Abstract
Internet trade pre-empts clinical trial.
An experimental cancer drug shrinks tumours in rats with no apparent side effects. The scientists behind the study plan to do a clinical trial in humans, but it could take years to complete. Meanwhile, dying patients begin taking the unapproved drug and collect their results on the web. Both groups desperately want to save lives: but which is the right route to follow?
This scenario has been playing out in recent weeks for a compound called dichloroacetate (DCA). It taps into long-running issues about whether terminally ill patients should be able to get access to drugs that have not yet had formal approval. Researchers fear that those taking the drug could suffer unanticipated side effects; patients argue they don't have the luxury of waiting for clinical trials to find out.
In January this year, Evangelos Michelakis at the University of Alberta in Edmonton, Canada, and his colleagues reported that DCA has seemingly remarkable anticancer properties (S. Bonnet et al. Cancer Cell 11, 37–51; 2007). DCA is a small molecule that blocks an enzyme in mitochondria — the energy-production centres in cells — causing more glucose to be metabolized in the mitochondria rather than by a different pathway in the cytoplasm. The compound has been in clinical trials for years as a treatment for certain mitochondrial diseases, but it has not yet been approved.
Michelakis says the patients could end up undermining efforts to do a controlled clinical trial if, for example, some develop harmful side effects and the drug earns a bad reputation. "It's destroying efforts to do this right," he says. "Any way you look at this, it's a negative development." An FDA spokesperson told Nature that the agency is looking into the matter.
The battle between dying patients who want immediate access to unapproved drugs and doctors who urge trials and caution is a perennial one. Some patients argue that they cannot wait for trials and should have the right to take unapproved drugs, regardless of the risks.
But there are arguments against this. An estimated 95% of cancer drugs that enter clinical trials do not get approval, many because they are ineffective or unsafe, so patients risk shortening their life or making their last days more uncomfortable. "They say what do I have to lose? The truth of the matter is, you have the rest of your life to lose," says George Annas, an expert in bioethics at Boston University School of Public Health.
And if patients can access DCA — or other unapproved drugs — there is no incentive for them to enter a clinical trial. So in terms of public health, ethicists argue, more people will be helped if access to unapproved drugs is restricted and proper trials performed.
Peter Jacobsen, an expert in ethics, health and law at the University of Michigan in Ann Arbor, doubts whether any good can come of the patients' efforts. They are so desperate to see results, he says, that there is no way they can report unbiased results and no mechanism to ensure the reports are accurate. "I don't trust the data," he says. "It's hard enough to rely on them in clinical trials, let alone this."

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