A new type of cancer drug developed at Johns Hopkins University in Baltimore, Maryland, but not yet tested in clinical trials may have triggered the deaths of three patients who were undergoing an alternative cancer treatment by a nonmedical practitioner in Germany. Germany has many such practitioners, and the field is loosely regulated. The public prosecutor in Germany is now investigating whether the case constitutes involuntary manslaughter.
The drug in question, 3-Bromopyruvate (3BP), has been hailed by some researchers as a potential breakthrough, but so far the only human data about its efficacy and safety are anecdotal. Many scientists say the drug should not be administered to patients except in carefully controlled experimental settings. If the link to the three deaths is confirmed, that could cloud 3BP's commercial prospects.
German police took action on 4 August after two patients from the Netherlands and one from Belgium died shortly after undergoing treatment at the Biological Cancer Centre, run by alternative practitioner Klaus Ross in the town of Brüggen, Germany, 50 kilometers west of Düsseldorf. Two other patients had to be treated for life-threatening conditions, the prosecutor's office said in a press release today. Police in Germany, the Netherlands, and Belgium have urged other patients treated at the center to contact local health authorities; at least 26 have done so. Media reports suggest that cancer patients often sought Ross's help after they ran out of conventional therapy options, or to avoid aggressive chemotherapy. He offered a 10-week “basic therapy” against cancer for €9900 ($11,057).
On his website, Ross touted 3BP as “currently the best compound to treat tumors.” In its press release, the prosecutor said the investigation has “reinforced” suspicions that the three deceased patients actually received the compound, as media interviews with relatives and other sources had previously suggested.
Ross did not respond to requests for comment from ScienceInsider. In a statement published on his website concerning the first death, he wrote that he is “in shock” and that he regrets the impression created in the media that alternative medicine may be responsible.
3BP, part of a class of compounds known as small molecule drugs, was first studied as an anti-cancer agent more than a decade ago at Johns Hopkins by biochemists Young Hee Ko and Peter Pedersen, together with radiologist Jeff Geschwind. It is believed to “starve” tumor cells to death by inhibiting glycolysis, the breakdown of glucose molecules to provide cells with energy. The hope is that 3BP specifically kills certain cancer cells—while leaving normal cells alone—because they rely more on glucose metabolism than on an alternative pathway called oxidative phosphorylation. In studies on rats and mice, 3BP was reported to reduce growth of tumors or even shrink them, and experiments on human cancer cell lines showed that combining another chemotherapeutic with 3BP increased its efficacy. However, animal studies also showed clear toxicity with certain administration regimes.
In 2009, Pederson and Ko teamed up with radiologist Thomas Vogl at the University Hospital Frankfurt in Germany for what appears to be a first experiment in a single patient. With the approval of the local ethics committee, a 16-year-old boy with a rare type of liver cancer called fibrolamellar hepatocellular carcinoma was given infusions of 3BP into the blood vessels supplying the tumor, formulated in a proprietary and patented fashion. Although he died at age 18, the researchers described the experiment as a success in a 2012 paper. “The rate of tumor necrosis due to 3BP treatment seems to exceed all known cytostatic drugs,” they wrote. No major toxic effects were observed, and the patient “was able to survive a much longer period than expected with an improved quality of life, which is clearly attributable to the treatment with 3BP,” the scientists concluded. In retrospect, Vogl says it would have been better to write “probably” instead of “clearly” because a single case report isn't strong evidence. Still, “we were surprised how long the patient survived and that we saw no toxic side effects,” he says.
A few other case reports have emerged more recently. For instance, in a paper published in 2014, Egyptian oncologists describe treating a 28-year-old man with 3BP; they reported that the compound appeared safe but not very effective if used alone.
But 3BP has yet to undergo formal clinical trials. PreScience Labs, a U.S. company founded by Geschwind, received approval for a phase I study from the U.S. Food and Drug Administration in 2013. Geschwind says the trial has yet to start because the company needs partners to finance it.
Both Vogl and Geschwind say they are concerned about inappropriate use of the drug. The 2012 paper co-authored by Vogl warned that “unformulated 3BP may be harmful in some cases,” and Vogl says doctors should “absolutely” not perform systemic infusions, in which the drug circulates through the entire body. “I am concerned about the drug being used without having first conducted the proper clinical studies,” Geschwind adds.
3BP can be purchased from chemical companies, and practitioners around the world offer it to patients. Local health authorities report that Ross says he obtained the compound from a German pharmacy. A spokesperson for the public prosecutor says that a preliminary assessment by health authorities has found that Ross was authorized to administer the substance; he declined to say how this was possible, given that 3BP is not approved.
Eugen Brysch, head of the German Foundation for Patient Rights in Dortmund, says that the government should regulate practitioners of alternative medicine more strictly. “Creativity in therapy must not negatively affect patent safety,” Brysch told a German newspaper. “It cannot be the case that plumbers or chip shops are supervised more strictly than medical service providers.”
A spokesperson for Germany's federal health ministry says there are no plans to overhaul regulation for traditional practitioners; local authorities are responsible for oversight of the field, she says. Those normally take action only after incidents or complaints, however. In the wake of the three deaths, the district of Viersen, where Ross had his center, has banned him from practicing in the district.