Lankheet N.A.G.,Slotervaart Hospital |
Kloth J.S.L.,Netherlands Cancer Institute |
Gadellaa-Van Hooijdonk C.G.M.,University Utrecht |
Gadellaa-Van Hooijdonk C.G.M.,Center for Personalised Cancer Treatment |
And 19 more authors.
British Journal of Cancer | Year: 2014
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. © 2014 Cancer Research UK.
Bins S.,Center for Personalised Cancer Treatment |
Schellens J.H.M.,Center for Personalised Cancer Treatment |
Voest E.E.,Center for Personalised Cancer Treatment |
Sleijfer S.,Center for Personalised Cancer Treatment
Nederlands Tijdschrift voor Geneeskunde | Year: 2014
• New possibilities for genetic diagnostics are rapidly assuming a place in oncological clinical practice. • Due to specific genetic aberrations, solid tumours characterised by their histological origin can now be further classified into subgroups. • The further sub-classification of tumours has led to the development of therapies that target these genetic changes. • Clinical research into these drugs in genetically characterised patient groups should be carried out more efficiently than is currently the case in oncological drug studies. • In both primary tumours and metastases, the heterogeneity of the tumour genome and the changes within this make the identification of important genetic aberrations more difficult. • In the Netherlands a network of hospitals and institutions is being set up - the Center for Personalized Cancer Treatment - to facilitate genome studies of tumours and clinical oncology studies and aimed at making the development of drugs more efficient.