Brazil's Phospho Cancer Cure Frenzy: A Cautionary Tale

Brazil's most unusual medical telenovela came to an end last month, after almost 2 years of unexpected and dismaying chapters. It starred a blue and white handmade capsule that claimed to "cure cancer," a retired chemistry professor, thousands of terminally ill cancer patients and their families, and even the country's former president, Dilma Rousseff.

Gilberto Orivaldo Chierice, the aforementioned chemistry professor, was tenured at the prestigious Universidade de São Paulo (USP). He produced and distributed for free capsules with synthetic phospholethanolamine (sold in the United States and Europe as the supplement Calcium EAP), claiming that it cured cancer – any type of cancer.

This went on for 20 years, until his retirement, in August 2015. It was only then that university president Dr Marco Antonio Zago tried to put an end to this practice, forbidding the capsule's production and distribution on the university's premises.

Until that moment, Chierice was an almost folkloric figure in São Carlos, a city in upstate São Paulo with a population of 250,000, two universities campuses, and well-known, high-tech research centers. Desperate patients, who used to count on Chierice and the university for the compound, protested, and local media went after the story.

It didn't take long for a national outlet to pick it up. Once G1, a news site owned by Globo, the largest media group in Brazil, ran the story on its front page, it instantly went viral, becoming national news. It sparked a public outcry demanding the immediate release of the so-called miracle drug, which until that point had never been clinically tested.

It also had not been approved by Anvisa, the national health surveillance agency, which is Brazil's version of the FDA.

"We doctors and medical associations failed to foresee how far this all would go," admitted Dr Gustavo Fernandes, president of the Brazilian Society of Clinical Oncology, a staunch critic of the "cancer pill."

Unprecedented Decision – Clinical Trial Funded

The public pressure was such that last year, in an unprecedented decision, the Instituto do Câncer do Estado de São Paulo (Icesp), a state-funded cancer hospital connected to the Universidade de São Paulo, started a clinical trial, using Chierice's formula and his prescribed dosage. That trial planned to enroll 210 patients of the institution who had 10 different types of cancer ― melanoma, colorectal cancer, cancer of the pancreas, liver, stomach, or prostate, non–small cell lung cancer, or breast, prostate, and cervical cancer.

On March 31, Icesp announced that the trial would stop enrolling patients because of "lack of clinical benefits"; of the 73 patients in the trial, 58 did not show any significant response. A response was seen in one melanoma patient, who experienced a reduction of more 30% of the tumor. This patient and another 12 who remain in the trial will finish the study's protocol. They will take the product for 2 months, after which they will undergo follow-up.

"The positive side of that story is that Brazil proved that it can design and conduct phases 1 and 2 clinical trials when there is interest and financial resources," said Dr Fernandes.

This result, in which no benefit was shown, is what Brazilian scientists and oncologists had been expecting since Chierice's claims has been made public, but it shocked Chierice's fans, who display a fierce, almost religious fervor in his defense. They vowed to continue their fight for access to the substance.

Discovery of the Substance

Chierice has a long list of published works, all in analytical chemistry, but the first article of his about the substance only appeared in 2011, 20 years after he supposedly started researching the drug.

Prior to that, Chierice had not published anything in the biological sciences.

In an interview with a small TV station, conducted in November 2015, Chierice said he had stumbled upon the compound around 1990 while researching scientific literature for an unrelated topic in chemistry and had found an article saying that the substance, commonly used in shampoo production and as a food preservative, was "cancerous."

That study, published in 1979, described phosphoethanolamine as a growth factor for a rat mammary carcinoma cell line. "I wanted to know why it produced cancer, but I've found out that the high concentration of phosphoetanolamine around the tumor was really the body defending itself from cancer. I was right, but alone, because at that time no one would say that phosphoetanolamine could cure cancer, but I interpreted it correctly," he stated in that interview.

There is no evidence in his documented research that he had conducted a biologic experiment to prove that hypothesis until the 2011 article appeared.

In other interviews, Chierice said he started to synthesize the substance in his laboratory. He sent it to be tested in another of part of the university campus. Afterwards, around 1995, he contacted Hospital Amaral Carvalho, in the nearby city of Jaú, asking to run clinical trials. The hospital confirmed Chierice's request but denied that the trials ever happened. The professor has repeatedly maintained that the trial not only happened but was successful, despite never producing any proof in the form of data, reports, prescriptions, or documents, nor has he named any of the physicians who, according to him, conducted the experiment.

Supposedly, the patients who were enrolled in the trial picked up the capsule at his university laboratory, but as the news spread through town, more and more people appeared at his door begging for the substance. Out of pity, he started gibing it to them for free. His laboratory allegedly produced 50,000 blue and white capsules a month. It has been said that over the next 2 decades, at least 20,000 patients took them.

Advised Patients to Stop Chemo and Radiotherapy

Rather worryingly, Chierice also started to advise the patients to stop undergoing chemotherapy and radiotherapy because they damaged the immune system, and becasue of that, the capsules would not work.

One patient was the wife of Marcos Garcia, a psychology professor at the Universidade Federal de São Carlos, also in São Carlos. "She had squamous cell carcinoma of the lung, and we tried everything. She entered clinical trial for Iressa (gefitinib), and we were happy because she felt better, but later we were told she was receiving a placebo. She decided to try the 'cancer pill' in December of 2002, and I went to the lab and asked for them. Chierice then personally told me she had to stop chemotherapy," Dr Garcia told Medscape Medical News in an interview. His wife died 3 months later.

As his capsules became more and more notorious, Chierice denied he had ever said that patients should stop undergoing conventional therapies, lest he might be accused of illegally practicing medicine, but he continued to say that the patient's immune system needs to be intact for the substance to work.

Chierice also said in a rare interview and at patients gatherings that cancer cells are also called differentiates (instead of transformed), that they all are "anaerobic," and that "their mitochondria are paralyzed." He also said that cancer cell division is "promoted" by the cells' "lack of energy," and mentioned caspases as a "process" and not as a family of proteases. Chierice has also proposed that because phosphoetanolamine has a natural affinity for cell membranes, it enters the cell and goes to the mitochondria, which then release caspases, inducing programmed cell death, which marks the tumor cells for destruction by the immune system.

These pronouncements "show a kindergarten level of understanding of how cancer cells work and how dynamic they are," according to Guido Lenz, a researcher at the Signalization and Plasticity Lab of Universidade Federal of Rio Grande do Sul, Porto Alegre, speaking in an interview with Medscape Medical News. Similar opinions were expressed by many Brazilian scientists in various news reports.

But for the general public, Chierice's spiel matched widespread beliefs that cancer is not only easy to cure but that Big Pharma has been hiding this fact to profit from toxic and useless drugs.

Brazilians nicknamed the substance 'phospho,' a term quickly picked up by the country's media, as well as cancer patients and their families. They clamored to have access to the product, and went to the courts to have injunctions passed to allow access.

Frenzy Over "Phospho"

If anything can portray the national debate's intensity and the heated furor over "phospho" in Brazil, it would be the reaction to a television segment aired on October 18, 2016, on Fantástico, a popular Sunday magazine show. Dr Drauzio Varella, an oncologist and well-known TV correspondent who has an office in a upperclass neighborhood in São Paulo, said that 23 of his patients were asking for the "phospho pill." He warned viewers to be cautious about the anticancer claims for this substance. The TV segment had not yet ended before Chierice's fans initiated a vicious attack on Dr Varella through Facebook, calling him "a merchant of death that profits from pharmaceutical companies" and inciting protests in front of his clinical office in São Paulo.

Dr Helano Freitas, coordinator of Clinical Research at the A. C. Camargo Cancer Center, another leading cancer hospital in São Paulo, told Medscape Medical News that the phospho frenzy made many patients refuse to enroll in clinical trials. "When I offered the chance of clinical trial for promising new drugs, a patient would say: 'Thanks, doctor, but I would only participate if it was a phospho clinical trial.' "

Stories of miracle cures were shared on social media to such an extent that many of the "phospho believers" ― a large number of whom were terminally ill cancer patients or their families ― said that this was enough to justify approval of the substance by the regulatory agencies as a drug.

Some researchers associated with Chierice supported such a view on their personal Facebook pages. For example, both Dr Renato Meneguelo, a general practitioner, and Durvanei Maria, an immunologist, have claimed in social media that the substance was not toxic or deleterious and, therefore, patients should be free to use it.

By that time, Chierice's off-the-record recommendations that the capsules should not be used by patients receiving chemotherapy or radiotherapy were public knowledge, and any endorsement of the substance could endanger the lives of many patients for whom viable treatment paths were still available.

Legal Moves

In November 2015, the University of Sao Paulo appealed to the Brazilian Supreme Court, because it could not comply with the numerous judicial orders to deliver the phospho capsules after Chierice's retirement, owing to the fact that this was the professor's pet project.

At the same time, Brazilian scientific and medical entities were denouncing the absurdity of this situation both nationally and internationally, as in this news article published in Nature.

Around that time, USP's weekly newspaper, Jornal da USP, published photos of Chierice's laboratory, showing rusted instruments, buckets for collecting water from leaks in the roof, dirty sieves, and windows open to the outside, raising risk for contamination. The newspaper article circulated in the chambers of the Brazilian Supreme Court and allegedly shocked some of the justices.

Politicians Became Involved

After the initial media reports, it did not take long for Brazilian politicians to catch a ride on the phospho wave. Many were already involved in corruption scandals, they saw in the "cancer pill" controversy as a chance to show they were on the people's side and could thereby redeem themselves with their constituents. They too started to demand approval of the 'phospho' pills, and invited the researchers to a series of hearings in the Brazilian National Congress.

Under such pressure, the Ministry of Science and Technology announced in November 2015 that it was providing funding in the form of a grant of US$3.3 million ― an extraordinary amount by Brazilian standards ― to test the product. In Brazil, where serious scientists struggle to get grants for research, this is a huge amount of money. Public universities were assigned to run the required first-stage tests for a future clinical trial. The results would take at least 7 months, which was too long to appease the public.

Geraldo Alckmin, governor of São Paulo State, who is himself a physician, received Gilberto Chierice with pomp and circumstance and vowed to do his best to help him. The clinical test ended on April 14. A private laboratory, PDT Pharma, in Cravinhos, which is owned by a former student of Chierice's, was choosen to produce the phosphoetanolamine for the tests, under direct supervision of the chemist's technician, Salvador Claro Neto, who took a leave from USP to oversee the work. The university quickly announced the definitive closure of the São Carlos's laboratory, and suddenly patients were again without the white and blue pills. A few weeks after that, new injunctions were issued, and PDT Pharma is now supplying patients with the substance.

On March 8, 2016, the Brazilian an House of Representatives approved passed a bill to allow phosphoetanolamine to be produced and sold to cancer patients who could provide medical proof of their condition and who would be required to sign a term of consent. This effectively bypassed the existing drug regulations and undermined the authority of Anvisa, the Brazilian Health Surveillance Agency. Since the beginning of the debate, Anvisa has taken a staunch position against approval of the untested substance for release to the public.

As the bill went through the legislative steps, the first results of the state-funded phosphoetanolamine tests were released. They showed that Chierice's pills did not have the 98% purity that had been claimed but only 30%. Morever, in vitro tests showed it had no effect on cultured cancer cells. Chierice accused the scientists of "bad faith" and implied that they had "bribed," or adulterated, the data. His followers took his the lead. On social media, they characterized the in vitro studies as stupid and laughable. Some made comments such as, "Everybody knows that 'phospho' needs to be processed in the liver to be activated, and cultured cells obviously do not have a liver."

The in vitro study was published the day before the Brazilian Senate approved the phosphoetanolamine bill, which authorized the production and commercialization of phosphoetanolamine. The bill was sent to President Dilma Roussef to sign into law. Roussef, herself a lymphoma patient whose cancer is in remission after treatment in one of the best hospitals in the country, was advised by Anvisa's comissioner not to sign it but to veto it. Politically cornered, threatened by impeding impeachment, and facing record low approval rates. Roussef signed the law on April 13, 2016.

A few days later, the Brazilian Medical Association went to the Supreme Court, questioning the constitutionality of the new law. A definitive decision is still pending. The University of Sao Paulo's request to the Supreme Court to not comply with the 16,000 patient injunctions to obtain the drug had been granted.

Yet another politician also jumped onto the phospho train. Geraldo Alckmin, São Paulo governor of the São Paulo State, who is himself physician, received Gilberto Chierice and vowed to do his best to help Chierice prove he could cure cancer. He offered $500,000 to run clinical trials on patients at the state's cost. It was the negative results from this trial that were announced last month.

Marcos Vinicius de Almeida and Dr Meneguelo are two researches who originally worked with Chierice. They recently broke with the their mentor and that they had patented a new formula in the United States and had licensed it as a dietary supplement. It is produced by a Florida laboratory and is being exported to Brazil. Anvisa, the health surveillance agency, allows individuals to import supplements for personal use only. Anvisa already ordered the company to change their publicity, which showed a picture of a woman with hair loss, implying that the pills capsules can be used to treat cancer.

Chierice's loyal fans, howerever, remain undefeated. Even after the Icesp fiasco, those loyal to Chierice are clamoring for a new clinical trial, using a different dosage and a new protocol. In a country plagued by economic crisis and recession, going through austerity measures that recently slashed its science budget by half, it is unlikely that a substance that showed no effect at all would get a second chance.

"The 'phospho' will continue as a dietary supplement, but without the aura of great science discovery that their messiahs attributed to it," said Dr Fernandes.

An investigation by São Carlos' police has found no evidence of any wrongdoing, quackery, the illegal practice of medicine, or the production and distribution of an illegal substance. The Universidade de São Paulo maintains an uncomfortable silence on the subject. It has not explained how this was had been happening on one its campuses for more than 20 years. Neither Chierice nor his assistant Salvador Claro Neto, who continues to work at the university, were officially reprimanded for their conduct.

This article was produced in collaboration with the Portuguese edition of Medscape.

Medscape Medical News © 2017 

Cite this: Brazil's Phospho Cancer Cure Frenzy: A Cautionary Tale - Medscape - Apr 19, 2017.