Background:Plasma exposure of sunitinib shows large inter-individual variation. Therefore, a pharmacokinetic (PK) study was performed to determine safety and feasibility of sunitinib dosing based on PK levels.Methods:Patients were treated with sunitinib 37.5 mg once daily. At days 15 and 29 of treatment, plasma trough levels of sunitinib and N-desethyl sunitinib were measured. If the total trough level (TTL) was <50 ng ml -1 and the patient did not show any grade ≥3 toxicity, the daily sunitinib dose was increased by 12.5 mg. If the patient suffered from grade ≥3 toxicity, the sunitinib dose was lowered by 12.5 mg.Results:Twenty-nine out of 43 patients were evaluable for PK assessments. Grade ≥3 adverse events were experienced in seven patients (24%) at the starting dose and in nine patients (31%) after dose escalation. TTLs were below target in 15 patients (52%) at the starting dose. Of these, five patients (17%) reached target TTL after dose escalation without additional toxicity.Conclusions:In a third of the patients that were below target TTL at standard dose, the sunitinib dose could be increased without additional toxicities. This could be the basis for future studies and the implementation of a PK-guided dosing strategy in clinical practice.,
British Journal of Cancer
Department of Medical Oncology

Lankheet, M., Kloth, J., Gadellaa-Van Hooijdonk, C. G. M., Cirkel, G., Mathijssen, R., Lolkema, M., … Steeghs, N. (2014). Pharmacokinetically guided sunitinib dosing: A feasibility study in patients with advanced solid tumours. British Journal of Cancer, 110(10), 2441–2449. doi:10.1038/bjc.2014.194