Q: What is the role of personalized medicine in treating pediatric cancer patients?

Prof. Dr. Alexandra Russo: Currently, approximately 80% of children with cancer can survive for more than 15 years but often with severe side effects of the therapy. However, in 20% of patients, established therapies and their “one size fits all” concept, unfortunately, are ineffective. 

Therefore, it is crucial to better understand the biology of these primarily refractory or recurrent tumors, especially the heterogeneity of childhood tumors which differ from tumors in adults.

The future challenge is to develop intelligent therapy combinations, along with excellent molecular diagnostics, to prevent the development of resistance and to minimize toxicity.

Q: In your opinion, when is personalized medicine particularly crucial?

Prof. Dr. Alexandra Russo: The primary goal for pediatric oncologists and pharmacists is to create treatment options for the remaining 20% of children without a long-term chance of recovery. However, personalized therapy is also suitable for children with familial cancer, i.e. a congenital genetic tendency to develop tumors that often results in high therapy toxicity. By targeting individual molecular changes, conventional chemotherapies may be modified, potentially reducing the risk of toxicity-induced complications, such as therapy-caused second tumors.

Innovative therapies include new drugs that are ideally administered orally. This method's advantage is that it avoids prolonged hospital stays and allows children to be cared for in their family environment. This can significantly improve the overall psychosocial situation for these families.

Early-phase pediatric clinical trials involving new, innovative drugs are crucial for the continued development of personalized oncological treatments in children.

Q: How does automated compounding technology contribute to your work? What benefits have you observed?

Prof. Dr. Alexandra Russo:: Children often face more challenges than adults in accessing innovative therapies due to a lack of safety data and authorization for pediatric use of new medicines. On average, it takes about 10 years after a drug is approved for adults before it becomes accessible to children.

Since 2007, the European Medicines Agency (EMA), the regulatory authority for medicinal products in Europe, has mandated the submission of a "Pediatric Investigational Plan" (PIP) before a new drug can be approved. The PIP is a pediatric testing concept that ensures the collection of pediatric data through clinical studies, aiming to make innovative and effective drugs available to children more quickly. This is often circumvented because the approval is specific to entities. The justification is then:” Children do not suffer from prostate or lung cancer”. 

In the context of personalized medicine, treatment is based not only on the entity itself but also on molecular changes in tumors. Consequently, new drugs could potentially be suitable for children if their tumors exhibit the same molecular changes. These drugs, already approved for adults with oncological diseases, only come in one or two doses for adults, so their use in children is considered "off-label use".

The pediatric dosage is determined by body weight or body surface area and changes over time as the child grows. Weight can also fluctuate significantly during chemotherapy, such as steroid treatment. We frequently encounter problems resulting from a lack of child-appropriate medicines. These issues include inaccurate dosing, an increased risk of adverse reactions, or ineffective treatment due to underdosing. 

Dr. Marija Tubic Grozdanis: While pharmacies can prepare individualized capsules or suspensions in the prescribed dosage, these extemporaneous formulations often have poor or inconsistent bioavailability, low quality, and low safety. This is typically due to insufficient personnel for handling carcinogenic, mutagenic, and toxic drugs, and the unavailability of necessary starting materials. 

Prof. Dr. Alexandra Russo: Furthermore, it's challenging for parents and caregivers to administer medication to children in the form of suspensions or capsule contents prepared at home. They must open the capsules under safety conditions, such as masks, gowns and gloves, and mix the powder with juices or food, like yogurt. These mixtures are often rejected or spat out by children. We are missing data on the stability of the medication for example in different pH values of the juices and therefore how much of the dose actually reaches the child. Clearly, there is an urgent need for more customized, safe, child-friendly, and tasty dosage forms, to ensure reliable and safe dosing. 

Dr. Marija Tubic Grozdanis: By using a validated automated compounding system, we can protect pharmacy and ward personnel from exposure to cytotoxic drugs. Moreover, manufacturing with a validated automated compounding process ensures that formulations have accurate and personalized doses with consistent quality attributes and stability. This process can also save time spent on preparation and cleaning procedures.

Q: How do you envision the future of personalized medicine? What are the main opportunities?

Prof. Dr. Alexandra Russo: The future of personalized medicine will extend beyond innovative medication. It will also address patient challenges that have been previously overlooked. This approach will include considerations for individual toxicity, pharmacokinetics, and genetics, leading to a customized efficacy profile. This profile will also account for the individual dosage of the medication. The concept of "one size fits all" will no longer apply to medication dosage. Key aspects will also include gender-specific medication and individual pharmacokinetics.

Dr. Marija Tubic Grozdanis: Individualized compounding of medication is a promising technology for personalized therapy. With a validated compounding process offering maximum flexibility and precision, we anticipate a transformation in how medication is tailored and administered to individuals.

The capability to compound "polypills" and controlled-release dosage forms will simplify administration, increasing treatment compliance and success.

Personalized medicine can have a significant role in overcoming drug shortages. Also, the near future may allow us to link medication use with patient data. This approach could achieve 100% environmental sustainability by reducing transport needs and packaging material.

Prof. Dr. Alexandra Russo & Dr. Marija Tubic Grozdanis: The path is clear for personalized medicine using automated compounding technology, despite the challenges of integrating this technology into healthcare settings under an evolving regulatory framework. We believe that the combination of personalized medicine and automated compounded medication has the potential to fundamentally enhance disease treatment and patient care in the future.