Sunitinib-Induced Hemoglobin Changes Are Related to the Dosing Schedule

Veldt, Astrid A.M. van der; Boven, Epie; Vroling, Laura; Broxterman, Henk J.; Eertwegh, Alfons J.M. van den; Haanen, J.

doi:10.1200/jco.2008.20.6151

Cited by 22 publications

(8 citation statements)

References 10 publications

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“…However, it has been speculated that blockade of VEGF signaling may modulate erythropoietin expression, ( 15,17 ) or VEGFR2 inhibition and subsequent reduction of nitric oxide may result in loss of intravascular fluid. ( 16 ) The pattern of BP change observed in the current study, an increase in BP within 1 week of the start of axitinib, followed by relative stability, was similar to that seen in a previous phase I study of axitinib in Caucasian patients. ( 7 ) Importantly, increases in BP were manageable with antihypertensive medication.…”

Section: Discussionsupporting

confidence: 86%

Effect of axitinib (AG‐013736) on fatigue, thyroid‐stimulating hormone, and biomarkers: A phase I study in Japanese patients

et al. 2009

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Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3. This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, antitumor activity, and recommended starting dose of axitinib in patients with advanced solid tumors. Twelve patients received single-dose axitinib 5 mg and were monitored for ‡48 h. Continuous 5 mg twice-daily dosing was then initiated. One patient had doselimiting toxicity (grade 3 proteinuria and fatigue). Common treatment-related adverse events were anorexia, fatigue, and diarrhea. Grade 3 treatment-related adverse events were fatigue and hypertension. Maximum axitinib plasma concentration occurred 1-4 h after steady-state dosing. Eleven patients experienced thyroidstimulating hormone elevation; time-course change and fatigue onset appeared to be related in some patients. Significant correlation was observed between thyroid-stimulating hormone change and area under the plasma concentration-time curve (AUC; r = 0.80, P = 0.005). Axitinib decreased plasma soluble vascular endothelial growth factor receptor 2 (s-VEGFR2), with significant correlation between change in s-VEGFR2 and AUC (r = )0.92, P < 0.0001). Fluorodeoxyglucose positron emission tomography revealed a substantial decrease in tumor metabolic activity associated with axitinib. Tumor size decreased in nine patients. The time-course of thyroid-stimulating hormone change appeared correlated with fatigue. There were significant correlations between thyroid-stimulating hormone or s-VEGFR2 and axitinib exposure. Axitinib 5 mg twice-daily is the recommended starting dose for Japanese patients. This trial is registered with ClinicalTrials.gov, identifier NCT00447005. (Cancer Sci 2010; 101: 963-968)

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Section: Discussionsupporting

confidence: 86%

Effect of axitinib (AG‐013736) on fatigue, thyroid‐stimulating hormone, and biomarkers: A phase I study in Japanese patients

et al. 2009

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“…In addition, functional imaging techniques may be significantly influenced by the hemodynamic changes that are caused by targeted agents, in particular by inhibitors of VEGF signaling. As treatment with these drugs is associated with an increase in blood pressure [150, 151], a decrease in heart rate [152], and a reduction in capillary density of the normal microcirculation [153], these hemodynamic effects may affect the kinetic parameters that are obtained by functional imaging, such as PET and DCE-MRI. Therefore, methods need to be developed that correct for blood pressure and cardiac output in the kinetic modeling of functional imaging techniques.…”

Section: Clinical Issues For Response Evaluation In Renal Cell Cancermentioning

confidence: 99%

Targeted therapies in renal cell cancer: recent developments in imaging

et al. 2010

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Targeted therapy has significantly improved the perspectives of patients with metastatic renal cell cancer (mRCC). Frequently, these new molecules cause disease stabilization rather than substantial tumor regression. As treatment options expand with the growing number of targeted agents, there is an increasing need for surrogate markers to early assess tumor response. Here, we review the currently available imaging techniques and response evaluation criteria for the assessment of tumor response in mRCC patients. For computed tomography (CT), different criteria are discussed including the Response Evaluation Criteria in Solid Tumors (RECIST), the Choi criteria, the modified Choi criteria, and the size and attenuation CT (SACT) criteria. Functional imaging modalities are discussed, such as dynamic contrast-enhanced CT (DCE-CT), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), dynamic contrast-enhanced ultrasonography (DCE-US), and positron emission tomography (PET).

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“…As illustrated above, this appears to be a class effect of many VEGF pathway-targeted agents. Some explanations have been given for this phenomenon including the emergence of erythrocytosis secondary to antiangiogenic agents use through increase in the hepatic production of erythropoietin secondary to hypoxic microenvironment induced by them [34,35]. Other possible explanations include the fact that lower anemia in ramucirumab-treated patients may be related to lower tumor burden in these patients.…”

Section: Discussionmentioning

confidence: 93%