2023-05-07 10:42:13
Up to now, patients with brain tumors cannot be treated with most cancer drugs
Quelle: Getty Images/Thana Prasongsin
Most people with glioblastoma do not have much longer to live. The treatment is difficult – partly because many active ingredients cannot be delivered to the brain in sufficient quantities. A new ultrasound method could change that.
MWith a special ultrasound, the blood-brain barrier can be temporarily opened in order to bring substances to treat a tumor into the brain. The method used leads to an average four to sixfold increase in drug concentration in the human brain, reports a US research team Specialist journal “The Lancet Oncology”. How this affects possible treatment successes, however, still needs to be clarified in further studies.
The blood-brain barrier is a barrier between the bloodstream and the brain. It protects the central nervous system from pathogens, toxins and messenger substances circulating in the blood – but it also makes the treatment of neurological diseases more difficult because many active substances cannot pass the barrier. For this reason, various strategies to overcome the blood-brain barrier have been worked on for years.
In addition to the use of focused ultrasound, research is also being carried out into how to transport active substances bound to certain proteins into the brain, explains Michael Platten, director of the neurological clinic at the University Medical Center Mannheim, who was not involved in the current study himself. “We’ve been working on such conjugates for a long time, but there hasn’t been any really good progress.”
Up until now, patients with brain tumors have not been able to be treated with most anti-cancer drugs because they hardly cross the blood-brain barrier. Manufacturers also specifically design active ingredients against other types of cancer so that they do not go into the brain, explains Platten, deputy spokesman for the neuro-oncological working group in the German Cancer Society (DKG). This would prevent damage there from the outset. There is a lack of agents specially developed for brain tumors – also because the group affected is rather small and the field is therefore not so attractive for manufacturers.
Chemotherapy was administered intravenously in each case
The current study included 17 people with glioblastoma, the most common malignant brain tumor in adults. The chances of survival are so far very low, those affected usually die within months, rarely within a few years. The patients had a recurrent glioblastoma, so the tumor had already returned after the first therapy.
Adam Sonabend’s team from Northwestern University in Chicago used a novel device in which ultrasound-activated microbubbles open the blood-brain barrier. It was implanted in the patient’s skull after each tumor operation. Treatment began a few weeks later. Patients were awake during the four-minute procedure, which was repeated every few weeks for months. Some received up to six cycles of treatment.
A brain tumor can grow back after treatment
Quelle: Getty Images/Science Photo Library RF/KATERYNA KON/SCIENCE PHOTO LIBRARY
The chemotherapy was administered intravenously in each case. The chemotherapeutic agents paclitaxel and carboplatin were used, as the team reports. Both can usually hardly cross the blood-brain barrier. Promising signs of efficacy have been seen in past studies in which paclitaxel was injected directly into the brains of patients with glioblastoma, it said. However, the injection is associated with serious side effects such as brain irritation and meningitis, explained Sonabend.
Neuro-oncologist Platten believes that newer, more targeted drugs are more promising. It is questionable whether paclitaxel and carboplatin bring about a noticeable improvement in brain tumors, and both active substances are also neurotoxic.
According to the team, side effects of the ultrasound method recorded included headaches during the procedure and, in some patients, temporary brain dysfunction, changes in the composition of blood cells and high blood pressure. Surgical complications or infections were not observed.
The doctors also recorded how quickly the blood-brain barrier closed again after the end of the ultrasound treatment. For the most part, this happens in the first 30 to 60 minutes after exposure. The protective function is therefore only overridden for a very short time. With the knowledge gained, the sequence of drug delivery and ultrasound activation can be optimized in order to be able to bring as much active substance as possible to the brain, the researchers explain.
Treatment is safe and well tolerated
According to the research team, the results of the phase 1 study show that the treatment is safe and well tolerated overall. A phase 2 clinical study is now underway for patients with recurrent glioblastoma. Participants receive a combination of paclitaxel and carboplatin using ultrasound technology. The aim is to investigate whether this prolongs their survival.
DKG expert Platten is skeptical. It should be questioned, for example, whether a concentration can be reached at all with the neurotoxic substances that have an effect on the tumor but do not yet show any relevant damage to the brain.
In principle, however, Platten also considers the use of focused ultrasound to be a promising approach. The current study shows a technological advance: The process can be better controlled via an implant than if it is carried out via a probe through the cranial bone – as has usually been the case up to now. The experts consider it very possible that the method will also be used for other brain diseases in the future.
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