Nature: Brazilian courts tussle over unproven cancer treatment

Phosphoethanolamine capsules were manufactured at the University of São Paulo.

Patients demand access to compound despite lack of clinical testing.

On 11 November, to the relief of many cancer researchers, a state court overturned earlier court orders that had obliged the nation’s largest university to provide the compound to hundreds of people with terminal cancer. Although the reversal applies only to requests for the drug by residents of São Paulo state, administrators at the university estimate that it covers about 80% of the orders they have received for the compound.

The compound, phosphoethanolamine, has been shown to kill tumour cells only in lab dishes and in mice (A. K. Ferreira et al. Anticancer Res.32, 95–104; 2012). Drugs that seem promising in lab and animal studies have a notoriously high failure rate in human trials. Despite this, some chemists at the University of São Paulo’s campus in São Carlos have manufactured the compound for years and distributed it to people with cancer. A few of those patients have claimed remarkable recoveries, perpetuating the compound’s reputation as a miracle cure.

Dismayed by this unofficial distribution of phosphoethanolamine, the university’s administration moved in September 2015 to shut it down. Patients took the university to court, and in October 2015, Brazil’s Supreme Federal Court ruled in favour of one plaintiff who wanted the right to try the compound. A lower court then began granting orders for the university to provide it to others. University officials say that they were soon overwhelmed by more than 800 requests.

“The decision not only ignored the opinion of medical specialists, but also overlooked the fact that the drug has only been tested on animals,” says bioethicist Volnei Garrafa at the University of Brasilia. “Such court decisions bring false expectations for patients and their families, creating turmoil in society and confusion between what is safe and what is not.”

The Brazilian constitution guarantees universal access to health care, and it is common in Brazil for patients to turn to the courts to access drugs that the state health-care system does not dispense because of their cost, says Garrafa. But phosphoethanolamine presents a different situation, he adds, because it is not really a ‘drug’ at all. It is not approved by Brazil’s National Health Surveillance Agency.

Those who argue that people who are terminally ill have a right to try experimental medicines saw the decision earlier this year as a significant victory. But to the university administration, drug regulators and cancer researchers, it showed blatant disregard for the basic scientific principle that a drug should be demonstrated to be safe and effective before being given to patients outside of a clinical trial.

“It’s a violation of the autonomy of the university,” says Marco Antonio Zago, a physician and president of the University of São Paulo. “We are seen as a factory to produce something that we do not believe should be done.”

Phosphoethanolamine is an important building block of the lipids that make up cell membranes. The compound can also act as a molecular signal that activates certain cellular processes. Although some studies do suggest that the compound may kill cancer cells in isolated cells and mice, it is not entirely clear how the compound brings about this response. Biochemist Durvanei Augusto Maria at the Butantan Institute in São Paulo believes that the compound may be imported into tumour cells and, once inside, trigger processes that cause the cell to self-destruct. Immunologist James Venturini at São Paulo State University and his colleagues have found that phosphoethanolamine may modulate the immune system’s response to cancer or affect cell division (M. S. P. de Arruda et al. Braz. Arch. Biol. Technol. 54, 1203–1210; 2011).

But to justify using phosphoethanolamine in people, Venturini says, one would have to rigorously test it in a series of clinical trials using human volunteers. “I strongly believe that double-blind, randomized clinical studies are necessary,” he says.

And even before such trials, further preclinical studies would have to be done, says Jailson Bittencourt de Andrade, secretary for research-and-development policy at Brazil’s science and technology ministry. The ministry plans to fund those studies, he says, and has already asked several research laboratories in the country to do the work. If those tests and subsequent clinical trials are successful, he says, the ministry will also fund the research needed to scale up phosphoethanolamine production to the quantities and quality needed for an approved drug.

That process will take years. In the meantime, lawyers representing people with cancer have vowed to appeal against the latest ruling. If those appeals succeed, de Andrade worries that people will not wait until all the tests are completed, and may even abandon conventional treatment in favour of phospho­ethanolamine. “Many patients have come forward and said they have tried the drug and it has worked for them,” he says. “So the other patients and their families — they want phosphoethanolamine now.”

NATURE