Monte Carlo simulations of the clinical benefits from therapeutic drug monitoring of sunitinib in patients with gastrointestinal stromal tumours.

PURPOSE: Therapeutic drug monitoring (TDM) is being considered as a tool to individualise sunitinib treatment of gastrointestinal stromal tumours (GIST). Here, we used computer simulations to assess the expected impact of sunitinib TDM on the clinical outcome of patients with GIST.

METHODS: Monte Carlo simulations were performed in R, based on previously published pharmacokinetic-pharmacodynamic models. Clinical trials with dose-limiting toxicity and patient dropout were simulated to establish the study size required to obtain sufficient statistical power for comparison of TDM-guided and fixed dosing.

RESULTS: The simulations revealed that TDM might increase time to tumour progression by about 1-2 months (15-31 %) in eligible patients. However, the number of subjects required for a sufficient statistical power to quantify clinical benefit of TDM guided is likely to be prohibitively high (>1000).

CONCLUSION: Although data from randomised clinical trials on the clinical impact of sunitinib TDM are lacking, our findings support implementation of sunitinib TDM in clinical practice. For rare cancers with well-defined exposure-response relationships, modelling and simulation might allow the optimisation of dosing strategies when clinical trials cannot be performed due to low number of patients.