For decades, childhood cancer treatment has relied on medicines that were often developed primarily with adults in mind. The active drugs may be effective, familiar, and widely used, but their formulation, strengths, dosage forms, stability, and handling requirements can make them difficult to use safely and accurately in children.
That gap is now receiving renewed attention from the World Health Organization (WHO).
As part of its first-ever invitation for manufacturers of childhood cancer medicines to seek WHO prequalification, the organization has prioritized six established cancer medicines for more child-friendly formulations: cyclophosphamide, etoposide, mercaptopurine, methotrexate, procarbazine and temozolomide.
The issue is not that these medicines are missing from oncology. They are already used in paediatric cancer treatment. The problem is that the formulations available today do not always meet the practical needs of infants, young children and adolescents.
And in paediatric oncology, formulation is not a minor pharmaceutical detail. It can determine whether the correct dose can be given accurately, whether a child can swallow the medicine, whether caregivers need to manipulate hazardous chemotherapy at home, and whether treatment can realistically be stored and delivered in resource-limited settings.
WHO Opens First-Ever Prequalification Pathway for 12 Childhood Cancer Medicines
Children Are Not Small Adults
Paediatric cancer treatment frequently requires dosing according to a child’s weight or body surface area. That dose also changes as the child grows and can require repeated adjustment throughout treatment.
A tablet or capsule developed primarily around adult doses can therefore create an immediate practical problem: the medicine may exist, but the available strength may be too high or insufficiently flexible for accurate paediatric dosing.
Young children may also be unable to swallow conventional tablets or capsules. In the absence of an appropriate formulation, medicines may need to be split, crushed, opened, dispersed or otherwise manipulated.
Research supporting WHO’s work on paediatric formulations has highlighted that such manipulation can complicate dosing and potentially affect drug exposure, tolerability and adherence.
With cytotoxic cancer medicines, another concern emerges: handling exposure.
Opening capsules, crushing tablets or otherwise manipulating chemotherapy can expose parents, caregivers and healthcare workers to hazardous drug particles. WHO’s target product profiles for several of the priority medicines specifically identify safe handling as an important consideration.
In other words, creating a child-friendly cancer medicine is not simply a matter of making a tablet smaller.
Six Familiar Medicines, Six Formulation Gaps
The six medicines now prioritized by WHO illustrate different versions of the same underlying problem:
- Cyclophosphamide
- Etoposide
- Mercaptopurine
- Methotrexate
- Procarbazine
- Temozolomide
All have established roles in paediatric oncology, but WHO’s Paediatric Drug Optimization process concluded that better age-appropriate formulations were needed. The organization subsequently developed individual Target Product Profiles (TPPs) describing what optimized versions of these medicines should look like.
The examples show how specific the challenges can become.
For etoposide, commonly available oral capsules in 50 mg and 100 mg strengths provide limited flexibility for young children. WHO’s assessment noted both difficulties with dose adjustment and patient acceptability, while manipulation of the capsules presents a hazardous-exposure concern. A lower-strength formulation could allow more precise dosing, including in metronomic and palliative treatment settings.
For mercaptopurine, an essential component of treatment for diseases including acute lymphoblastic leukemia, the conventional 50 mg tablet can be difficult for younger children to swallow and provides limited dosing flexibility. A liquid formulation exists in some markets, but WHO identified issues including access, cost, excipients, packaging and shelf life. In settings where alternatives are unavailable, tablets may instead be crushed or dosing schedules modified.
Methotrexate presents another example. WHO identified a need for more easily titratable non-liquid oral options such as minitablets, dispersible tablets or coated multiparticulate formulations. The organization also identified opportunities to improve liquid formulations, including their stability and suitability for resource-limited settings.
For procarbazine, WHO highlighted the need for lower strengths and more flexible formulations, such as minitablets or dispersible tablets, that could allow more appropriate dosing for children.
And for temozolomide, WHO’s work has examined lower-strength and dispersible formulations that could give clinicians greater flexibility in adjusting doses. At the same time, because temozolomide is cytotoxic, formulation design must reduce the risk of direct exposure when the medicine is handled.
These are not six cases of missing anticancer agents. They are examples of a less visible problem: existing drugs whose available forms do not fully match the patients who need them.
What Does a “Child-Friendly” Cancer Medicine Actually Look Like?
WHO’s target product profiles move beyond identifying the problem. They give manufacturers a technical blueprint for what better products should achieve.
The organization is prioritizing formulations that allow flexible dosing through approaches such as dispersible or orodispersible tablets, minitablets, and multiparticulates. But dosage form is only one consideration.
WHO also wants formulations that can remain stable in hot and humid environments, preferably with shelf lives exceeding 24 months; that have acceptable taste and palatability; that include clear instructions allowing caregivers to handle them safely; and that can be produced sustainably at prices compatible with access in low- and middle-income countries.
That combination is important.
A formulation that works well in a highly resourced hospital but requires continuous refrigeration, complex preparation or specialized handling may be far less useful in a health system where supply chains are fragile or treatment takes place far from major cancer centers.
Designing medicines for children therefore also means designing them for the environments in which those children receive care.
The Gap Is Largest Where Childhood Cancer Survival Is Lowest
Around 400,000 children and adolescents develop cancer every year, according to WHO. Close to 90% live in low- and middle-income countries.
Yet survival exceeds 80% for children with cancer in many high-income countries while remaining below 30% in many lower-income settings. WHO identifies limited access to quality-assured medicines and the lack of formulations suitable for children among the factors contributing to this divide.
The formulation problem sits within a much larger access challenge, but it is an important one.
A medicine cannot deliver its full benefit if the appropriate strength is unavailable, if families must manipulate cytotoxic tablets to obtain a child’s dose, if the formulation cannot tolerate local storage conditions or if its price makes routine procurement unrealistic.
This is why WHO’s approach has increasingly connected pharmaceutical development with access from the beginning rather than treating them as separate problems.
The six target product profiles were developed following WHO’s first Paediatric Drug Optimization exercise for cancer medicines, held in January 2024. Technical consultations followed, along with input from paediatric oncologists, pharmacists, formulation experts, researchers, manufacturers and other stakeholders.
In 2026, those priorities moved one step further: the six medicines were included in WHO’s first childhood cancer Expression of Interest for prequalification, creating a pathway through which manufacturers can develop and submit optimized products for WHO assessment.
From an Old Drug to a Better Medicine for a Child
The story of childhood cancer innovation is often told through new drugs, targeted therapies and increasingly sophisticated technologies.
But innovation can also mean redesigning an old medicine so that a three-year-old can receive the correct dose without a parent having to crush a cytotoxic tablet.
It can mean creating a formulation that survives transportation in a hot climate, remains stable long enough to reach hospitals with irregular supply chains, and can be administered safely without sophisticated equipment.
WHO’s work on these six medicines reflects a broader shift toward considering the needs of children at the product-development stage rather than adapting adult medicines after the fact.
As Martina Penazzato, GAP-f Lead at WHO, said when the target product profiles were released:
“Every child with cancer deserves medicines that are safe, effective, and suitable for their age.”
For cyclophosphamide, etoposide, mercaptopurine, methotrexate, procarbazine, and temozolomide, the active medicines already exist.
The next challenge is ensuring that the medicine in the package is designed for the child receiving it.
Read further on OncoDaily: WHO Unveils 2026–2030 Strategy to Close the Childhood Cancer Medicines Gap
