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

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 10-20 days of each 42-day cycle. Total trough levels (TTL) C min of sunitinib and its active metabolite were measured every 6 weeks.

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 C min 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.

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.

Cancer chemotherapy and pharmacology. 2017 Jun 30 [Epub ahead of print]

Dhanusha Sabanathan, Alison Zhang, Peter Fox, Sally Coulter, Val Gebski, Bavanthi Balakrishnar, Mathew Chan, Christopher Liddle, Howard Gurney

Westmead Hospital, Sydney, NSW, 2145, Australia., Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia., NHMRC Clinical Trials Centre, Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown, NSW, 2050, Australia., Westmead Hospital, Sydney, NSW, 2145, Australia. .