Dose individualization of sunitinib in metastatic renal cell cancer: toxicity-adjusted dose or therapeutic drug monitoring.

Abstract

Dose individualization of sunitinib has been proposed using therapeutic drug monitoring (TDM) or toxicity-adjusted dose (TAD). We prospectively studied aspects of TDM and TAD to inform future trials, namely (1) intrapatient variability (CV) of sunitinib and (2) feasibility of a TAD protocol. Sunitinib dose was adjusted to ensure grade 1 or 2 toxicity on 10-20days of each 42-day cycle. Total trough levels (TTL) C min of sunitinib and its active metabolite were measured every 6weeks. In 45 patients with mRCC, 283 TTL samples were assayed over a median 30weeks (6-108weeks). Fifteen patients (33%) had an intrapatient CV of >25% in TTL. Ninety-one percent achieved target toxicity with a final sunitinib dose of 25mg (18%), 37.5mg (27%), 50mg (50%), and 62.5 or 75mg (7%). TTL C min was <50, 50-100, and >100ng/mL in 7 (15%), 31 (69%), and 7 patients (15.5%), respectively. The median overall survival was 32months. Sunitinib level has minimal variability in the majority of patients on stable dose. A subset of patients had a significant intrapatient variation, so we recommend two samples 4 to 6months apart. TAD is feasible for dosing sunitinib and showed a favourable outcome.