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Erschienen in: Cancer Chemotherapy and Pharmacology 2/2017

30.06.2017 | Original Article

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

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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2017

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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) C min 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 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.

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.
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Metadaten
Titel
Dose individualization of sunitinib in metastatic renal cell cancer: toxicity-adjusted dose or therapeutic drug monitoring
verfasst von
Dhanusha Sabanathan
Alison Zhang
Peter Fox
Sally Coulter
Val Gebski
Bavanthi Balakrishnar
Mathew Chan
Christopher Liddle
Howard Gurney
Publikationsdatum
30.06.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 2/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3362-1

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