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

作者：Sabanathan Dhanusha; Zhang Alison; Fox Peter; Coulter Sally; Gebski Val; Balakrishnar Bavanthi; Chan Mathew; Liddle Christopher; Gurney Howard^*

来源：Cancer Chemotherapy and Pharmacology, 2017, 80(2): 385-393.

DOI：10.1007/s00280-017-3362-1

• Sunitinib
• Individualized dosing
• Therapeutic drug monitoring
• Renal cell cancer
• Pharmacokinetics

Purpose 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.
Methods Sunitinib dose was adjusted to ensure grade 1 or 2 toxicity on 10-20 days of each 42-day cycle. Total trough levels (TTL) Cmin of sunitinib and its active metabolite were measured every 6 weeks.
Results In 45 patients with mRCC, 283 TTL samples were assayed over a median 30 weeks (6-108 weeks). Fifteen patients (33%) had an intrapatient CV of >25% in TTL. Ninety-one percent achieved target toxicity with a final sunitinib dose of 25 mg (18%), 37.5 mg (27%), 50 mg (50%), and 62.5 or 75 mg (7%). TTL Cmin was < 50, 50-100, and > 100 ng/mL in 7 (15%), 31 (69%), and 7 patients (15.5%), respectively. The median overall survival was 32 months.
Conclusions 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 6 months apart. TAD is feasible for dosing sunitinib and showed a favourable outcome.

• 出版日期2017-8