by ecancer reporter Clare Sansom

In the latest step in a months-long dispute, a court in the Brazilian state of São Paulo has voted to deny cancer patients access to a compound that has shown promise in cell and animal models of cancer but has not yet been tested in humans.¹

This compound, phosphoethanolamine, is manufactured and is being tested by researchers at Brazil’s largest university, the University of São Paulo.

For some years, chemists at the university have unofficially made it available to cancer patients, and a few of these have reported remarkable cures, which understandably increased demand.

Phosphoethanolamine is a member of a class of compounds termed antineoplastic phospholipids (APs), which are synthetic analogues of lysophosphatidylcholine.

These compounds are believed to kill tumour cells through interfering with lipid signal transduction, although their exact mechanism of action is unclear.

They are thought to have cytotoxic effects against a wide variety of tumour types, including some that show resistance to more conventional drugs.

Some APs have been tested in clinical trials, and one, miltefosine, is in clinical use for the treatment of cutaneous metastases in breast cancer; it is also an effective broad spectrum anti-microbial agent.

In 2012, Adilson Kleber Ferreira and co-workers at the University of Sao Paulo published pre-clinical studies of phosphoethanolamine that indicated its promise as a potential anti-tumour agent.²

The researchers showed, first, that the compound induced cell death through apoptosis in a range of human and murine cancer cell lines with IC50 values in the range of 1-3 mg/ml but had no effect on normal human cells.

In vivo tests in mice inoculated with Ehrlich ascitic tumour (EAT) cells - an experimental cell line derived from mouse mammary carcinoma - showed that phosphoethanolamine reduced tumour size and increased survival time in the mice without inducing significant toxicity.

The legal tussle over this putative but still unproven drug started in September 2015 when the university administrators restricted its unofficial distribution, and cancer patients began a hearing to restore access.

In Brazil, patients have often used the courts to try to access drugs denied them because of their high cost; the difference in this case is that phosphoethanolamine has not yet been approved by the country’s National Health Surveillance Agency so it is not yet a ‘drug’ at all.

Initially, the Supreme Federal Court in Brazil ruled that one cancer patient should continue to have access to the compound, and lower courts began instructing the university to provide it to others.

They received over 800 requests for the drug, mostly from the local area.

Volnei Garrafa, a bioethicist at the University of Sao Paolo, told Nature that these decisions, which overlooked the fact that phosphoethanolamine had not been tested for safety and efficacy in human trials, were likely to create false expectations in patients and their families.

The latest decision to deny access overturns the previous ones in the state of São Paulo only, but this affects over three-quarters of the requests received.

It is very likely that some of the patients who have now been denied access to the compound will appeal against the ruling, and this process is likely to take some years.

Researchers have received funding from the federal government in Brazil for further pre-clinical tests, and are planning to take the compound forward to clinical trials if these are successful.¹

An accompanying Nature editorial^3 ​praises the courts’ decision to deny access to phosphoethanolamine, pointing out potential problems with the current manufacturing process and suggesting that its availability may lead patients away from proven treatments.

It further suggests that the best options for patients interested in this approach will be to keep an eye on the research and, should the remaining animal studies confirm the compound’s promise, to enrol on a clinical trial.

References

1. Ledford, H. (2015). Brazilian courts tussle over unproven cancer treatment. Nature 527, 420-421. 

2. Ferreira, A.K., Meneguelo, R., Pereira, A,. Filho, O.M.R., Chierice, G.O. and Maria, D.A. (2015). 'Anticancer Effects of Synthetic Phosphoethanolamine on Ehrlich Ascites Tumor: An Experimental Study', Anticancer Research 32. 95-104.

3. Editorial (2015). Drugs on demand. Nature 527, 410.