Individualized dosing schedule of sunitinib switched through plasma concentration monitoring in patients with metastatic renal cell carcinoma.

Abstract

694 Background: The aim of this study was to investigate the survival benefit and safety of switched dosing schedules for sunitinib in Chinese patients with metastatic renal cell carcinoma through plasma concentration monitoring. Methods: One hundred and twelve patients with mRCC were enrolled who were treated with Sunitinib. Patients were classified into 3 groups: switched dosing schedule through plasma concentration monitoring (4/2-2/1 schedule, 4/2-2/1-individualized and 2/1-individualized schedule), switched dosing schedule empirically due to severe adverse events (AEs)(4/2-2/1 schedule) and dosing schedule without switching (initial 4/2 or 2/1 schedule).The blood samples of patients in monitoring group were collected at different medication points consecutively within one or two course of treatment. In monitoring group, dosing schedule was switched according to plasma concentration curve. For patients whose dosing schedule was switched empirically, the switching was from 4/2 to 2/1 schedule because of intolerance to initial 4/2 schedule. The survival benefit and safety were compared among these 3 groups. Results: From plasma concentration curves, dosing schedules were switched in 17 patients. The dosing schedule was switched from 4/2 to 2/1 in 37 patients empirically, while 58 patients were administrated with a 4/2 or 2/1 schedule without switching. Among the monitoring, empirical and initial group, the median PFS was 30.0,20.0 and 9.0 months,respectively(P = 0.001), and the median OS was not-reach, 37.0, and 18.0 months, respectively (p = 0.004). Moreover, patients with a switched schedule through monitoring had better tolerance after switching. The incidence of grade 3/4 AEs fell from 88.2% to 41.2% (p = 0.001).In empirical group, the incidence of grade 3/4 AEs fell from 73.0% to 37.8% (p = 0.001). Conclusions: Treatment-related toxicities could be minimized through plasma concentration monitoring. Patients with switched schedules by monitoring could achieve a better survival benefit.