Dose individualization of sunitinib in metastatic renal cell cancer

toxicity-adjusted dose or therapeutic drug monitoring

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

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)385–393
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume80
Issue number2
DOIs
Publication statusPublished - Aug 2017

Keywords

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

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