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Published on: February 6, 2019
Dose finding in pediatric patients
1Charité Campus Virchow Klinikum, Berlin, Germany. guenter.henze@charite.de
Abstract:
It is generally agreed that satisfactory safety and effectiveness of pharmaceutical products for children and adolescents have not yet been established. This applies in particular to anti-cancer drugs and even to those having successfully been used for many years in multidrug chemotherapy protocols for childhood cancer. For example, nephroblastoma or Wilms' tumor is one of the typical and frequent forms of childhood cancer occurring at a median age of about 3 years. Standard therapy for Wilms' tumor is the combination of vincristine and actinomycin D; survival is about 85%. For actinomycin D, the summary of product characteristics states that one contraindication is children aged below 6-12 months. If this would be considered and respected it would mean that a substantial proportion of children with Wilms' tumor would not be treated and thus a proven curative therapy would be withheld. The current situation in pediatrics is that off-label use has become a common practice: in private practice about 20% of prescriptions are off-label, in children's hospitals approximately 40%-50% with 50%-70% in pediatric oncology and more than 90% in neonatology (Conroy et al. 1999, 2000, 2003; Turner et al. 1996, 1998; McIntyre et al. 2000). These conditions are more or less tolerated by the authorities although they are beyond legality. The reason is that appropriate clinical trials like those in adults have not been conducted in children and drugs have therefore not been licensed.
Insights
Pediatric cancer drug safety and effectiveness are not well-established, leading to widespread off-label use. Clinical trials are needed to ensure safe and legal treatments for children with cancer.
Area of Science:
- Pediatric Pharmacology
- Oncology
- Drug Safety
Background:
- Pharmaceutical product safety and effectiveness in pediatric populations, especially for anti-cancer drugs, remain inadequately established.
- Established chemotherapy protocols for childhood cancers often involve drugs with contraindications for young children, posing treatment dilemmas.
Purpose of the Study:
- To highlight the critical gap in established safety and efficacy data for pediatric pharmaceuticals, particularly in oncology.
- To underscore the prevalence and implications of off-label drug use in pediatric medicine due to lack of licensed alternatives.
Main Methods:
- Review of existing literature and clinical practices concerning pediatric drug use and off-label prescribing.
- Analysis of the challenges posed by contraindications in standard pediatric cancer therapies, such as Wilms' tumor treatment.
Main Results:
- Off-label prescription rates are high in pediatric settings, ranging from 20% in private practice to over 90% in neonatology.
- Standard pediatric cancer treatments, like that for Wilms' tumor, rely on drugs with age-related contraindications, necessitating off-label use.
Conclusions:
- The widespread off-label use of drugs in children is a tolerated but legally questionable practice, driven by a lack of pediatric-specific clinical trials and drug licensing.
- Urgent need for conducting rigorous clinical trials in pediatric populations to establish safe and effective drug options, ensuring legal and ethical treatment standards.
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