Chemotherapy – there’s no denying it’s a scary-sounding word. But, despite the heart-breaking images that it can conjure, it has saved the lives of many people diagnosed with cancer. If you’ve read the ‘How has childhood cancer research changed since the 1800s?’ blog, you’ll know that the introduction and advancement of chemotherapy during the 20th century made a big difference to children with cancer, playing a key part in improving childhood cancer survival rates from only one in ten children surviving their cancer in the 1950s to now over eight in ten.
These are fantastic improvements, however, there is now more awareness of toxic side effects that can happen with chemotherapy. Many children with cancer face the prospect of developing long-term adverse effects (called late effects) from their treatment, with a higher risk for some patients.
Recently, the top ten childhood cancer research questions were announced, following an intense series of workshops. They considered questions from children, parents, families, and childhood cancer professionals to find the biggest problems facing children with cancer.
There is no doubt that finding kinder and more effective treatments is the top priority for childhood cancer researchers, but development of new medicines takes a lot of time and investment. We need to help the children who are going through treatment now – to make sure that having had cancer doesn’t mean they can’t have a happy and fulfilling life. So, if we don’t have any new ‘wonder drugs’ on the horizon, how can we change things for the better?
Where is change needed?
One of the most difficult challenges for children’s cancer doctors and pharmacists is deciding how much chemotherapy to give to certain patients, such as very young babies and children, who may process medicines differently than older children. The stakes are high - too much chemotherapy could lead to long-term side effects, but too little could allow the cancer to grow and spread. There are guides for getting the dose right, based on a child’s weight or surface area, but these are not always accurate for the harder to treat patients.
This is where Professor Gareth Veal comes in. His research focuses on understanding what happens to drugs when they are given to patients, and how differences in how the body processes these drugs can impact their response to treatment. He said, “it’s hard to think of a more important area for my research team to work in than childhood cancer.”
It’s vital that we continue to treat patients as effectively as possible but also that we do everything possible to limit the side effects from chemotherapy, many of which can affect survivors of childhood cancer for the rest of their lives.
“It became increasingly apparent that our research focus had the potential to help cancer doctors facing incredibly challenging decisions on what drugs and doses to give to hard-to-treat patients, such as babies in the first weeks of life.”
His team was receiving huge numbers of enquiries from doctors asking for support making these difficult choices for their patients. There were so many requests for help that Gareth applied for funding from The Little Princess Trust, in partnership with CCLG, realising that guidance was needed at a national level.
In November 2021, his research project started. The goal was to make sure that every patient who joined the project received the right amount of chemotherapy. Gareth’s team are working on a process called ‘therapeutic drug monitoring’ to give every child the best chance of beating their cancer.
What is therapeutic drug monitoring?
As a patient goes through treatment, doctors take blood samples during each treatment cycle. The research team then measures the amount of the chemotherapy drug in the child’s bloodstream to check the medicine isn’t reaching toxic levels but is still high enough to fight the child’s cancer.
When treating babies in the first days or weeks of their lives, it can be difficult to know how their body will process chemotherapy medicines. Gareth said, “as the development of organs such as the liver and the kidneys will still be undergoing considerable change at this young age, it’s really difficult to know what dose of chemotherapy will lead to the most beneficial drug exposure in an individual child.”
By collecting blood samples during and following treatment, our research team are able to measure drug levels in patients and work out whether they may benefit from more or less drug.
“Essentially, too high a drug exposure is more likely to lead to side effects of treatment, whereas too low a drug exposure means that the patient is less likely to benefit from the treatment. We really want all patients to achieve drug exposures that are somewhere in the middle - an area that we call the ‘drug therapeutic window’.”
Gareth’s team has worked on clinical trials testing chemotherapy treatments for many years, so were able to quickly establish how they would measure the levels of chemotherapy drugs in patient’s blood tests. Knowing that this project could help many more children if it becomes standard clinical practice nationally, Gareth said he needed to find “a team of people who are experienced in setting up clinical trials and dedicated lab-based staff who are willing to work unsociable hours when needed in order to analyse patient’s blood tests.” Luckily, his fantastic research team at Newcastle University had these skills and shared his drive to help young children with cancer.
How is it benefitting patients?
So far, this project has helped close to 100 patients, and Gareth is aiming to increase this number to 200 patients by the end of 2023. He has found that monitoring drug levels via blood tests has often resulted in the team suggesting changes to patients’ chemotherapy doses. However, he said, “in some cases our research might not lead to a change in dose but provides the patient’s doctor with confidence that they are getting the drug exposure right.”
“We have identified quite a few drugs where very young patients being treated in the first weeks of life may be being under dosed, and this has led to changes to dosing regimens at a national level. This shows that the positive impact of the study is much wider than the patient population who directly participate.”
Gareth’s team won the ‘Innovation in Practice’ award at the 2022 CCLG Member Awards for fantastic innovation, and the impact this project will have for many children with cancer. His project will finish next year, and we look forward to seeing his results!
You can read more about the project, or check out Gareth’s academic papers below.
Publications
- A Population Pharmacokinetic Modelling Approach to Unravel the Complex Pharmacokinetics of Vincristine in Children
- Perspectives and Expertise in Establishing a Therapeutic Drug Monitoring Programme for Challenging Childhood Cancer Patient Populations
- Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients: A case series
Ellie Wilkinson is CCLG’s Research Communication Executive.
She is using her lifelong fascination with science to share the world of childhood cancer research with CCLG’s fantastic supporters.
You can find Ellie on Twitter: @EllieW_CCLG