Survey on off-label use of antineoplastic agents in pediatric patients using a large-scale medical database in japan

A number of drugs without pediatric indication are used off-label in infants and children who are described as "therapeutic orphans". This practice is widespread and constitutes a global issue. We conducted a drug utilization study using a large-scale electronic medical record(EMR)database to explore off-label prescription of anticancer drugs in pediatric patients. The EMR database was provided by Medical Data Vision(MDV). The subjects of the present study were pediatric patients aged from 0 to 14 years who were prescribed anticancer drugs and enrolled in the database between January 2016 and December 2017. We surveyed the number of patients who were prescribed these drugs outside the approved age window. Of 700 pediatric patients included in this study, 277 patients(40％) were prescribed anticancer drugs off-label; especially, 182 patients were prescribed"cytotoxic antibiotics and related substances"according to the WHO ATC classification, predominantly pirarubicin(140 patients). Since pirarubicin has not been approved in overseas countries, it is difficult to apply for pediatric indication utilizing the development promotion schemes such as the"public knowledge-based application(kouchi-shinsei)", and other drug development schemes have to be considered. Only a few subjects(0 to 3％)were prescribed anticancer drugs with pediatric indication but outside the approved age range. The prescribed doses［median(min-max)］of methotrexate and cytarabine were 15(2.8-21200)mg and 60(3-9000)mg, respectively. The dose ranges of these drugs were wide compared to the other drugs in the study. It was speculated that these high doses were probably used as high-dose therapy according to clinical guidelines, within the framework of clinical research. Considering that anticancer drugs generally have narrow safety margins, drug development for approval of pediatric indication should be promoted to provide safe and effective treatments for pediatric patients.