Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis

Houk, Brett E.; Bello, Carlo L.; Poland, Bill; Rosen, Lee S.; Demetri, George D.; Motzer, Robert J.

doi:10.1007/s00280-009-1170-y

Cited by 429 publications

(420 citation statements)

References 19 publications

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“…A meta‐analysis found AUC of sunitinib combined with its active metabolite N‐desethylsunitinib to be significantly associated with PFS and OS in both GIST ( n = 401) and RCC ( n = 169), all P < 0.01 76. An increased OS was found for an AUC ≥1,973 ng*h/mL in another study in RCC patients ( n = 55) 74…”

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 98%

“…In RCC, increasing AUC has been related to higher response rates, longer PFS, and OS 74, 75, 76, 77. A meta‐analysis found AUC of sunitinib combined with its active metabolite N‐desethylsunitinib to be significantly associated with PFS and OS in both GIST ( n = 401) and RCC ( n = 169), all P < 0.01 76.…”

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 99%

See 1 more Smart Citation

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

233

287

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Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is highly variable and clear relationships exist between exposure and treatment outcomes, fixed dosing is still standard practice. This review aims to summarize the available clinical pharmacokinetic and pharmacodynamic data into practical guidelines for individualized dosing of KIs through therapeutic drug monitoring (TDM). Additionally, we provide an overview of prospective TDM trials and discuss the future steps needed for further implementation of TDM of KIs.

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Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 98%

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 99%

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

233

287

View full text Add to dashboard Cite

show abstract

“…Increased understanding of the pathogenesis of sunitinib-associated side effects may allow rational administration to patients. Optimizing sunitinib treatment is essential, as increased exposure is associated with improved clinical benefit (75). In a meta-analysis of data from patients with metastatic RCC and GIST, increased exposure was associated with longer time to progression, overall survival, higher probability of a response, and greater decrease in tumor size, but also with more adverse events, albeit of mild-tomoderate intensity in most patients (75).…”

Section: Discussionmentioning

confidence: 99%

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Aparicio-Gallego

Blanco

Figueroa

et al. 2011

Molecular Cancer Therapeutics

106

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The introduction of targeted therapy represents a major advance in the treatment of tumor progression. Targeted agents are a novel therapeutic approach developed to disrupt different cellular signaling pathways. The tyrosine kinase inhibitor sunitinib specifically blocks multiple tyrosine kinase receptors that are involved in the progression of many tumors. Sunitinib is the current standard of care in first-line treatment of advanced renal cell carcinoma, and it is approved in imatinib-intolerant and imatinib-refractory gastrointestinal stromal tumors. However, it is increasingly evident that sunitinib may display collateral effects on other proteins beyond its main target receptors, eliciting undesirable and unexpected adverse events. A better understanding of the molecular mechanisms underlying these undesirable sunitinib-associated side effects will help physicians to maximize efficacy of sunitinib and minimize adverse events. Here, we focus on new insights into molecular mechanisms that may mediate sunitinib-associated adverse events. Mol Cancer Ther; 10(12); 2215-23. Ó2011 AACR.

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“…The results showed that patients with the highest AUC experienced longer overall survival (OS), longer time to progression and greater tumor size reduction. Tentative relationships were also identified between total drug exposure and the incidence of fatigue, reduction in neutrophil counts and diastolic hypertension [10].…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%