Poster Presentation Advances in Neuroblastoma Research Congress 2016

Background Due to concerns over extensive 13cisRA pharmacokinetic variability, we previously utilised a therapeutic drug monitoring (TDM) approach to target a defined drug exposure in high-risk neuroblastoma patients (Clin Cancer Res 2013;19:469-479). Findings suggested that current dosing regimens may be pharmacologically suboptimal in patients receiving reduced body weight–based 13cisRA dosing and children unable to swallow 13-cisRA capsules, with drug extracted before administration. We now have 3 year clinical follow-up for the patients recruited to this trial.

Methods Patients received 13cisRA alongside ch14.18/CHO as maintenance therapy on the HR-NBL1/SIOPEN trial. 13cisRA (160mg/m² or 5.33mg/kg/day for patients <12kg) was administered to 72 children and dose increases of 25-50% were implemented on consecutive courses to achieve peak plasma concentrations ≥2µM as required. EFS was calculated from the start of 13cisRA treatment. An event was defined as relapse, disease progression or death.

Results 13cisRA dose increases were implemented in 21 patients who experienced plasma concentrations <2µM. 3 year EFS rates for patients receiving standard versus TDM 13cisRA were 51% and 67%, respectively. With the limited patient numbers, there was no statistically significant difference between these groups (P = 0.1113).

Conclusions The current study involved selecting patients experiencing the lowest 13cisRA exposures and utilising a TDM approach to individualise treatment. Despite small numbers of patients, data generated raise the question as to whether high-risk neuroblastoma patients may benefit from increased doses of 13cisRA, either based on a TDM approach or more practically, involving dose increases to achieve a maximally tolerated dose in individual patients.