Background: Pediatric anticancer drug development has numerous challenges. The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were passed to address pediatric drug development deficiencies in general. Until recently, the requirements for pediatric evaluation of most oncology products developed for adult cancers have been waived. Because children typically do not have the same type of cancers, which occur commonly in adults, or the indication or drug had been granted an orphan designation, PREA therefore has had no impact. Pediatric studies for labeling updates are largely done through BPCA by a written request (WR) issued by the Food and Drug Administration (FDA). Because the cancers that occur in pediatric and adult populations do not share the same etiology or natural history, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The characteristics of individual pediatric studies included in WRs have varied greatly over time. Procedure: In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics, which had been accepted by sponsors. Results: Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and three drugs that were studied have been approved for use in pediatric populations. Herein, we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidentiary standard of efficacy, and safety perspective. Conclusions: This provides information on requests issued in the past nearly 20 years and studies that are completed. As WRs have provided the only regulatory mechanism to assure pediatric cancer drug development, this can potentially provide insight on how pediatric cancer drug development may change in the future.

Cancer remains the leading cause of death from disease in children. Historically, in contrast to their adult counterparts, the causes of pediatric malignancies have remained largely unknown, with most pediatric cancers displaying low mutational burdens. Research related to molecular genetics in pediatric cancers is advancing our understanding of potential drivers of tumorigenesis and opening new opportunities for targeted therapies. One such area is fusion oncoproteins, which are a product of chromosomal rearrangements resulting in the fusion of different genes. They have been identified as oncogenic drivers in several sarcomas and leukemias. Continued advancement in the understanding of the biology of fusion oncoproteins will contribute to the discovery and development of new therapies for childhood cancers. Here we review the current scientific knowledge on fusion oncoproteins, focusing on pediatric sarcomas and hematologic cancers, and highlight the challenges and current efforts in developing drugs to target fusion oncoproteins.

Protein binding significantly influences pharmacokinetic properties of drug distribution. Albumin accounts for approximately 60% of the total plasma protein by mass, thereby making it the major protein in the body. Hypoalbuminemia, a type of hypoproteinemia, is a condition of abnormally low blood albumin levels. Hypoaluminemia causes pharmacokinetic issues in regards to dosing a patient's medication. The purpose of this paper is to review the role of the coadministration of albumin in hypoalbuminemic patients to optimize pharmacotherapy.

Background Pediatric anticancer drug development has numerous challenges. The PREA and the BPCA were passed to address the deficiency in pediatric drug development in general. Until recently, the requirement for pediatric evaluation of most oncology products has been waived, because children typically do not have the same type of cancers which occur commonly in adults or the indication or drug had been granted orphan designation. PREA therefore had no impact. Pediatric studies for labeling updates are largely done through BPCA by a Written Request, issued by FDA. Because pediatric and adult populations do not share the same biology, natural history, or disease progression, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The requirements for the pediatric studies have varied greatly over time. Procedure In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics which had been accepted by sponsors. Results Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and 3 drugs that were studied have been approved for use in pediatric populations. Herein we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidential standard of efficacy and safety perspective. Conclusions This provides information on requests in the past nearly 20 years and studies completed. As WRs are the anchor of pediatric cancer development for the time being, this can potentially provide insight on how pediatric cancer drug development may change in the future.