'USP cancer pill' was never clinically tested

Cancer patients and their relatives have filed legal proceedings to gain access to a capsule manufactured by the São Carlos Institute of Chemistry from the University of Sao Paulo (IQSC-USP) which they believe is effective against cancer. Unregistered by the National Health Oversight Agency (Anvisa) [FDA equivalent], the institute only continues production of synthetic phosphoethanolamine capsules because of the legal proceedings.

The substance, which was first synthesized by an IQSC researcher in the late 1980s, never went through the research and trial steps necessary for a medication to be developed, as a result of which there is no scientific evidence that the product is effective in fighting cancer or safe for human consumption.

Start of production

Chemist Gilberto Orivaldo Chierice, a retired professor at the IQSC, began researching the substance in the 1980s and started working on the hypothesis that it had anticarcinogenic properties. He went on to develop his own method for synthesizing the substance in the laboratory.

The process for testing the safety and possible therapeutic properties of a compound are lengthy and involve various stages of research that were not carried out in the case of synthetic phosphoethanolamine.

Research stages

First, a candidate substance for conversion to a medication must be tested on simpler models, such as a cell, explains scientist Vilma Regina Martins, Head of Teaching and Research at the A.C. Camargo Cancer Center.

The product must then undergo testing on animals with the aim of verifying whether the drug is capable of controlling a tumor in a living organism, for example. During this phase, testing is carried out on rodents and non-rodents. This stage is also capable of establishing whether the substance has any significant toxic effect or if it is safe for use.

Should all the results prove favorable, clinical trials on human beings begin in the next phase. Phase 1 clinical trials evaluate the safety and toxicity of the product in humans, generally on healthy volunteers.

Phase 2, which is carried out on a larger number of patients, begins to test the effectiveness of the drug against the condition in question. Phase 3 involves a much larger number of patients and is generally carried out in various centers in different countries. Only once this has been completed can the product be submitted to the regulatory agency (to Anvisa, in the case of Brazil) so that the request for registration may be evaluated.

Each of these phases must be approved by the competent bodies such as the Comitê de Ética e Pesquisa [Ethics and Research Committee — CEP], the Comissão de Ética em Pesquisa [Ethics and Research Commission — Conep] and Anvisa itself. “All treatments must have a scientific basis: this is evidence-based medicine. Anything else is charlatanism, not science.” says Vilma.

According to Chierice, in the case of the synthetic phosphoethanolamine, the only test to which the substance was subjected after having been synthesized by the IQSC was that of the lethal dose, which verifies the amount of the substance capable of killing half of a population of laboratory animals. Chiarice states that the substance did not cause the death of a single guinea pig and that he concluded that it would be safe to test it on humans.

According to the researcher, after this the capsules began to be dispensed to cancer patients at the Hospital Amaral Carvalho in Jaú with which the IQSC had an agreement as result of another project. According to Chiarice, the drug was dispensed via the signing of an informed consent form by patients, many of whom were in the final stages of the disease.

However, the hospital which specializes in cancer stated in an email to G1 that it had no record of the use of the capsule by patients of the institution.

Snowball effect

Chiarice says that, despite the lack of evidence on the effects of phosphoethanolamine on these patients, “some people experienced an improvement” and word of the existence of a “USP cancer pill” began to spread. Even after the hospital ceased dispensing the product to patients, some relatives continued showing up at the IQSC to request new prescriptions and the institute continued producing it to meet that demand.

“Patients improved and recommended it to their neighbors. No one controlled this to start with, none of us were physicians. They’d say: ‘I’d like to take some for my cousin as I’m sure it will do them good.’ Our attitude was not to police that,” says the researcher.

The scientist himself admits that he doesn’t know what the appropriate dose of the drug is. “In what dosages did people take it? The same as that dispensed by the hospital. We had no means of making clinical recommendations, we weren't physicians, we didn’t have the competence to make any such statement. They were already showing up on the recommendation of a neighbor, of a coworker. It was extremely hard to control. This snowballed and by 2013 we were producing over 50 thousand capsules per month.”

Anvisa: No request for clinical trials was ever made

Anvisa declares in a statement that no request for authorization for clinical trials to evaluate the effectiveness of synthetic phosphoethanolamine against cancer was ever made, nor any request to register the product as a medication.

Chiarice accuses Anvisa of “ill will” for not having helped him carry out the preclinical and clinical trials necessary to evaluate the drug. Anvisa counters that it is not the role of the agency to conduct research and develop medications. “It should be underscored that Anvisa only evaluates clinical trials or requests for the registration of medications and other products when these have been requested by the interested party. In other words, the Agency does not perform analyses without an objective reason,” states the institution in an email.

The agency further noted that “the sale or distribution of any unregistered medication or one lying outside the context of an approved clinical trial is illegal.”

More recently, a partnership between Chiarice and the Instituto Butantan resulted in the publication of five articles in scientific journals on the anticarcinogenic effectiveness of synthetic phosphoethanolamine on cell cultures and in animals. However, no progress was made on tests to establish the viability of a study on humans.

An approach was also made to the Fundação Oswaldo Cruz (Fiocruz) in November 2013 to proceed with the tests, but no agreement was signed. According to Chiarice, that institution demanded that the patent for synthesizing the substance be transferred to Fiocruz, which would not have been accepted by the researcher. Fiocruz responds by claiming that no patent request was made, but that it only stated that in order for potential widescale manufacture of the drug capsules to take place, the licensing of the drug should be transferred to an official laboratory following completion of the necessary trials.

Legal proceedings

The institute ceased production of the capsule following Chiarice’s retirement from the IQSC in 2013. The institute claimed in a statement that it had established that since neither the license nor the registration necessary for production of the drug for medical purposes was available, such distribution was in violation of federal legislation.

Several patients have therefore filed proceedings with the legal authorities to claim the right to receive the drug, which is why IQSC continues manufacturing and supplying the product to meet legal requirements.

“It should be underscored that IQSC has no data on the effectiveness of phosphoethanolamine in treating various types of cancer in human beings, because we are not aware of the existence of any clinical oversight of patients taking the drug — and we lack the physicians to guide and prescribe usage of the aforementioned drug,” stated the institute.

Risk to patients

In the opinion of researcher João B. Calixto, head of the Centro de Inovação e Ensaios Pré-clínicos [Center for Innovation and Pre-Clinical Trials — CIEnP], a private research entity providing services to pharmaceutical companies, this situation is atypical and could place patients at risk. “Situations like this probably occurred more frequently in the past, but increasingly strict laws that are aimed chiefly at the safety of the patient have been in place for a long time,” he said. “What you have in this case is just one molecule that was not synthesized for the target illness, but by chance. Today, the industry does not create a molecule by chance, but based on a target it wants to attack.”

Meanwhile, hundreds of patients continue seeking out Chierice to request the “USP cancer pills” as they believe these to be capable of curing cancer. There is no record of the number of people who have recourse to this drug and none on the effect of the capsule on the patients.

5 questions and answers on the PHOSPHOETHANOLAMINE case

1) What is it? A substance that started to be produced in a laboratory by a researcher (since retired) at USP that is believed to be effective in treating cancer.

2) What’s the controversy? Cancer patients have filed legal proceedings to obtain the product from USP, but the compound was never subject to the legally required tests. USP has responded to the complaint solely because it is legally obliged to do so.

3) But is it effective against cancer? Scientifically there is no means of stating that it is because the necessary tests were never carried out. It has been dispensed for several types of cancer but without there being any scientific evidence that this is appropriate.

4) Why weren’t the tests carried out? The researcher claims that they requested assistance from Anvisa to carry out the necessary tests, but that there was “ill will” from the agency. The agency, for its part, states that no request for authorization of clinical trials was ever made. Fiocruz was also contacted, but the researcher states that that institution demanded that the patent for synthesizing the substance be transferred to the foundation, which he would not have accepted. Fiocruz responds by stating that no patent request was ever made.

5) What harm can be caused by using this product? Given that its effects are unknown, there is no way of excluding side effects. The researcher who discovered how to synthesize it himself admits not knowing what dosage would be sufficient to treat cancer.

Original article published in Portuguese in G1.