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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages385–393
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume80
Issue number2
DOIs
Publication statusPublished - Aug 2017

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Drug Monitoring
Renal Cell Carcinoma
Toxicity
Monitoring
Pharmaceutical Preparations
Drug-Related Side Effects and Adverse Reactions
Metabolites
sunitinib
Survival

Keywords

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

Cite this

Sabanathan, Dhanusha ; Zhang, Alison ; Fox, Peter ; Coulter, Sally ; Gebski, Val ; Balakrishnar, Bavanthi ; Chan, Mathew ; Liddle, Christopher ; Gurney, Howard. / Dose individualization of sunitinib in metastatic renal cell cancer : toxicity-adjusted dose or therapeutic drug monitoring. In: Cancer Chemotherapy and Pharmacology. 2017 ; Vol. 80, No. 2. pp. 385–393.
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Dose individualization of sunitinib in metastatic renal cell cancer : toxicity-adjusted dose or therapeutic drug monitoring. / Sabanathan, Dhanusha; Zhang, Alison; Fox, Peter; Coulter, Sally; Gebski, Val; Balakrishnar, Bavanthi; Chan, Mathew; Liddle, Christopher; Gurney, Howard.

In: Cancer Chemotherapy and Pharmacology, Vol. 80, No. 2, 08.2017, p. 385–393.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Dose individualization of sunitinib in metastatic renal cell cancer

T2 - Cancer Chemotherapy and Pharmacology

AU - Sabanathan, Dhanusha

AU - Zhang, Alison

AU - Fox, Peter

AU - Coulter, Sally

AU - Gebski, Val

AU - Balakrishnar, Bavanthi

AU - Chan, Mathew

AU - Liddle, Christopher

AU - Gurney, Howard

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