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06.05.2016 | Original Research Article | Ausgabe 10/2016 Open Access

Clinical Pharmacokinetics 10/2016

Population Pharmacokinetic/Pharmacodynamic Modeling of Sunitinib by Dosing Schedule in Patients with Advanced Renal Cell Carcinoma or Gastrointestinal Stromal Tumor

Zeitschrift:
Clinical Pharmacokinetics > Ausgabe 10/2016
Autoren:
Reza Khosravan, Robert J. Motzer, Elena Fumagalli, Brian I. Rini
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s40262-016-0404-5) contains supplementary material, which is available to authorized users.

Abstract

Background

Sunitinib is a multi-targeted tyrosine kinase inhibitor used in the treatment of advanced renal cell carcinoma (RCC) and imatinib-resistant/intolerant gastrointestinal stromal tumors (GIST).

Methods

A meta-analysis of 10 prospective clinical studies in advanced RCC and GIST was performed to support the development of pharmacokinetic (PK) and PK/pharmacodynamic (PD) models that account for the effects of important covariates. These models were used to make predictions with respect to the PK, safety, and efficacy of sunitinib when administered on the traditional 4-weeks-on/2-weeks-off schedule (Schedule 4/2) versus an alternative schedule of 2 weeks on/1 week off (Schedule 2/1).

Results

The covariates found to have a significant effect on one or more of the PK or PD parameter studies included, age, sex, body weight, race, baseline Eastern Cooperative Oncology Group performance status, tumor type, and dosing schedule. The models predicted that, in both RCC and GIST patients, Schedule 2/1 would have comparable efficacy to Schedule 4/2, despite some differences in PK profiles. The models also predicted that, in both indications, sunitinib-related thrombocytopenia would be less severe when sunitinib was administered on Schedule 2/1 dosing compared with Schedule 4/2.

Conclusion

These findings support the use of sunitinib on Schedule 2/1 as a potential alternative to Schedule 4/2 because it allows for the management of toxicity without loss of efficacy.

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Zusatzmaterial
Supplementary material 1 (DOCX 41 kb)
40262_2016_404_MOESM1_ESM.docx
Supplementary material 2 (PDF 1818 kb)
40262_2016_404_MOESM2_ESM.pdf
Literatur
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