A well-known drug can keep a common herpesvirus quiet when people with brain cancer are at their most vulnerable. In a small trial, the same treatment appeared to delay the cancer returning – and may, in time, become a gentle way of buying patients more time.
In the most aggressive form of brain cancer, glioblastoma, the period after surgery is crucial. The cancer almost always returns, and radiotherapy and chemotherapy can simultaneously put the immune system under such strain that a dormant virus wakes up.
A new study among people with glioblastoma suggests that valganciclovir, a drug used against cytomegalovirus, can keep the virus quiet during this critical period – and may give some patients several more months before the cancer starts to grow again.
“The antiviral drug can completely prevent the virus from flaring up, precisely while patients are receiving radiotherapy and chemotherapy. This is the crucial time, because cancer treatment weakens the immune system,” says Mattia Russel Pantalone, a doctor and researcher from the Karolinska Institutet in Stockholm, Sweden.
The study is small and needs to be confirmed before the treatment can change clinical practice. The research has been published in Cancers.
Cancer treatment can wake a sleeping virus
Glioblastoma is the most aggressive form of primary brain cancer, and most people with glioblastoma live for only 12 to 15 months after diagnosis. This means that even a few extra months without relapse can be very important.
The disease is relatively rare, but for those affected, there are few good options.
Cytomegalovirus belongs to the herpesvirus family and is widespread. Many people carry it in their bodies, where it can hide for the rest of their lives, rarely causing harm in healthy people.
However, the virus can wake up and become dangerous to people with weakened immune systems, such as people with cancer. In glioblastoma, this can happen precisely during the treatment meant to keep the disease down.
The new study builds on the VIGAS1 trial, which began in 2006. Now, the stored blood samples enable a new question to be asked: could a virus that wakes up during treatment help to bring relapse forward?
The trial involved 42 patients with newly diagnosed glioblastoma. They first underwent surgery and then received standard treatment with the chemotherapy drug temozolomide and radiotherapy.
They were randomly assigned to two groups: one receiving valganciclovir on top of their usual treatment and the other a placebo. The trial was too small to provide a definitive answer, but it could show whether an old drug appeared to affect the trajectory of a disease in which relapse is almost the rule.
Blood tests showed when the virus woke up
Blood samples had been taken at the start and after 3, 12 and 24 weeks. This enabled Mattia Russel Pantalone to follow whether cytomegalovirus woke up along the way.
The result was clear in the blood tests: none of those who received valganciclovir showed signs that the virus flared up during the critical treatment period.
In the placebo group, by contrast, 58% of those who were already carrying cytomegalovirus showed signs of reactivation.
“The interesting thing is that this reactivation happened exactly after 12 weeks. That corresponds to the end of radiotherapy and chemotherapy, when the immune system is under the greatest strain,” says Mattia Russel Pantalone.
The blood tests showed immunoglobulin M (IgM) antibodies, which the researchers used as a sign that cytomegalovirus was active again. IgM is not the same as measuring the virus itself directly but suggested that the virus had woken up. IgG antibodies showed who was already carrying the virus in their body.
Corticosteroids made it easier for the virus to wake
Another clue was corticosteroids, which patients are often given to treat swelling in the brain.
Corticosteroids reduce the swelling and can make surgery easier. But they also suppress the immune system and can give a dormant virus a better chance to wake up. In the trial, higher doses were associated with more frequent reactivation. This does not prove that corticosteroids were the cause, but it fits with the suspicion.
Here too, valganciclovir appeared to offer protection.
“We cannot avoid corticosteroids, because they work very well and make patients feel better. But one of the unfortunate side-effects is that they can wake dormant viruses. If we give an antiviral drug alongside them, we might be able to avoid exactly that,” explains Mattia Russel Pantalone.
Once the virus had flared up, relapse came early. Already around three months after the operation – while many others are still hoping that the treatment will keep the disease down.
For those who were already carrying cytomegalovirus and received valganciclovir, relapse took longer. In this group, 6.7 months elapsed on average before the cancer returned versus 3.7 months among those who received a placebo. The difference may be clinically important in glioblastoma, but it applied only to this group and needs to be confirmed in a larger trial.
“We think that we should give the antiviral drug to patients who are about to undergo radiotherapy and chemotherapy and who already carry the virus. In that way, we can hopefully prevent the virus from waking up and the cancer from returning early,” says Mattia Russel Pantalone.
However, the researchers cannot yet say whether the antiviral drug prolongs overall survival. Several participants in the placebo group were later given valganciclovir outside the trial’s randomisation, making that question harder to answer based on VIGAS1.
Cells and mice pointed to the same vulnerable window
To determine whether the connection made biological sense, the team used both cancer cells and mice.
In glioblastoma cells carrying cytomegalovirus, viral activity increased when the cells were exposed to corticosteroids. The antiviral drug slowed production again.
The same pattern appeared in mice. Animals carrying the virus and receiving radiotherapy and high doses of corticosteroids had far more active virus in their blood. When they were given the antiviral drug, reactivation was inhibited. This does not in itself show what happens to humans, but it supports the biological explanation.
The next test is VIGAS2, a larger trial involving 220 participants. It will show whether the strategy can actually give people with glioblastoma more time – or whether the indication from the small trial does not hold up.
The trial will determine whether the antiviral drug can delay relapse when it is given specifically to those who already carry cytomegalovirus and have the dormant virus in their bodies before cancer treatment begins.
The results are expected in late 2027.
“This is still a small trial with preliminary results, but they all point in the same direction. If, in the large trial, we can confirm that a single, well-known antiviral drug can protect these patients from the virus waking up, while also keeping the cancer at bay for longer, it will be a gentle way to help some of the very sickest cancer patients,” says Mattia Russel Pantalone.
