TORONTO — A cheap generic drug that caused a big buzz a few years ago when it was found to shrink tumours in laboratory rats may provide a key for treating one of the deadliest cancers in humans, researchers say.
Reporting in the journal Science Translational Medicine on Wednesday, scientists at the University of Alberta say they tested the compound DCA (dichloroacetate) in five people with brain tumours known as glioblastomas.
The drug, which alters the way cancer cells metabolize nutrients to stay alive and keep on multiplying, was found to have positive effects in most of the patients. Brain scans showed tumour growth in four of the patients was arrested after 15 months of treatment. In three, the tumours shrank.
But co-lead investigator Dr. Evangelos Michelakis, a professor of medicine, stressed that much more research on many more patients is needed before any conclusions can be drawn about DCA’s effectiveness in treating glioblastomas.
“This paper was not supposed to announce the results of a trial, this is very few patients,” he said from Edmonton. “The main objective of this paper was to determine what the mechanism of DCA is in humans with glioblastomas, because you cannot extrapolate from animals.”
In 2007, Michelakis and his team published a study of rats with lung, breast and brain cancer that had been treated with DCA, a generic drug used for many years to treat children with congenital metabolic diseases.
Their finding that DCA caused the animals’ tumours to shrink created a huge stir, leading hundreds of cancer patients to buy the drug via the Internet and through other for-profit sources, even though it is not approved in Canada or the U.S. for treating malignancies.
Nor had it, at that point, been tested on humans with cancer.
Michelakis, while encouraged by the latest results in people, warned that cancer patients who self-medicate with DCA purchased from unregulated sources could be putting themselves in danger.
“People sell it and most of the time one doesn’t know what is the real source, purity or whether that stuff is actually DCA,” he said of the white powder taken orally.
“The usual excuse that people say is: ’What do I have to lose?”’ said Michelakis. But a person’s health can get much worse. One glioblastoma patient in the study appeared not to respond to DCA and died after about three months on the drug; another had worsening of the tumour initially, although its growth eventually slowed.
Because DCA builds up slowly in the bloodstream, it takes time to become effective, he said. “Pretty much this means if you have an aggressive cancer and you drop any other drug and you start getting DCA because you think this is going to help you, for the first few months you’re not even exposed to adequate levels of DCA.”
“And fast-growing tumours can actually kill you these first few months because they grow uncontrolled.”
Michelakis said side-effects from DCA’s interactions with other drugs are also unpredictable, and too high a dose can cause peripheral nerve malfunction.
“That can actually be very severe, to the point that the patient will not be able to walk anymore. This is why this is risky.”
Still, the researchers say their preliminary findings in people suggest that DCA or other drugs that disrupt cancer cells’ metabolism may provide a new avenue for treating cancer.
“We show that metabolism can be a target for cancer in human beings.”
Dr. Abhijit Guha, a neurosurgeon at the University Health Network in Toronto, said there is a sound rationale for testing DCA, but agreed cancer patients should not be taking the drug outside a carefully controlled clinical trial.
Guha, who was not involved in the study, said glioblastomas and indeed most cancers arise because of a multitude of factors — and one drug is unlikely to be the answer to treatment.
“If we look at this particular compound and look at the few patients that are being proposed, I don’t think you can take any conclusion that this particular agent works or doesn’t work,” he said, but added that DCA could be viewed with “cautious optimism.”
The Canadian Cancer Society was still reviewing the study Wednesday, but echoed that note of caution.
“As for any clinical trial, it is important to ensure the treatment is safe and effective,” Gillian Bromfield, senior manager of cancer control policy, said by email.
“Until these clinical trials are finished, we can’t advise cancer patients in the general population to use the agent. The society will continue to monitor this issue and update our information if warranted.”