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The best dose for every child

Like Quinn (7), almost all children with cancer will receive chemotherapy at some point in their treatment. By measuring the concentration of a drug in the blood, the dose can be better adapted to the individual child. Dr. Inge van der Sluis: ‘We are taking steps towards personalized treatment in many different ways.’

This article is part of Childhood Cancer Awareness Month.

Treatment for children with cancer is increasingly tailored to the individual child. For example, a child diagnosed with a higher or lower risk form of the disease will be offered a heavier or less intensive treatment plan.

Dr. Inge van der Sluis, pediatric oncologist specialized in leukemia: ‘The DNA of the leukemia cells and how the leukemia responds to the first month of treatment gives us increasingly more information about how aggressively the disease behaves. These factors determine in which risk group the child will be treated. You can give much less therapy to children in a low-risk group without lowering the chance of a cure. That’s important, because it means a child will also experience fewer or less severe side effects. In children with a higher risk, we intensify the therapy to increase the chance of a cure.’

Blood levels
‘In many different ways, we are taking steps toward personalized treatment,’ says Van der Sluis. ‘One of those steps is therapeutic drug monitoring. We measure the levels of the drug in the blood. This is important because medicines can behave slightly differently in each child: there can be a difference between the amount of medicine you’re given and what actually ends up in the cancer cells. The blood levels of a drug can end up being very different, even between children who given the same dose.’

One of the medicines that is monitored in this way is asparaginase, a chemotherapy that is part of the standard treatment for all children with acute lymphoblastic leukemia (ALL). ‘The most commonly used form of asparaginase does not work for all children,’ says Van der Sluis. ‘We use therapeutic drug monitoring to pick out children in whose blood the drug is broken down too quickly. This chemotherapy does not work for them, so we can switch to another variant of asparaginase that does work against their leukemia.’

Fewer side effects
Monitoring levels in the blood can also help reduce nasty side effects of chemotherapy. Van der Sluis: ‘When we began measuring asparaginase levels ten years ago, we saw that they were much too high. Then we started adjusting the dosage to the blood levels. We noticed that nausea was much reduced in children whose levels had been too high and for whom we were able to lower the dose.’

As well as asparaginase, therapeutic drug monitoring is used with the chemotherapy drug methotrexate and for example with a class of targeted drugs called tyrosine kinase inhibitors, including the drug imatinib. But there is still a lot to learn, says Van der Sluis. ‘For many drugs, we don’t yet know exactly how high the blood level should be for them to be effective. In these cases we’re sticking to the dose that we have always used.’

‘Thanks to (international) research, we are continually making discoveries about how chemotherapy and other medicines for children with cancer really behave in the body. For example, why do some children experience a particular side effect and others don’t? We are constantly taking steps to tailor the treatment exactly right, so we can offer a child the best chance of recovery with optimal quality of life.’