What question did this study set out to answer?

To investigate whether circulating plasma levels of VEGF, sVEGFR-2, sVEGFR-3, and PlGF serve as pharmacodynamic and response biomarkers during sunitinib treatment.

July 2, 2007Journal of Translational MedicineOpen Access

Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins

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Authors

SDSamuel E. DePrimoPoseida Therapeutics (United States)CBCarlo L. BelloPfizer (United States)JSJohn SmeragliaAstraZeneca (United Kingdom)

Discussion

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Implication

Phase II trial reveals modulation of circulating VEGF-related proteins by sunitinib in metastatic renal cell carcinoma, indicating their utility as dynamic biomarkers of drug activity.

Key Points

To investigate whether circulating plasma levels of VEGF, sVEGFR-2, sVEGFR-3, and PlGF serve as pharmacodynamic and response biomarkers during sunitinib treatment.
Enrolled 63 patients with metastatic renal cell carcinoma refractory to first-line cytokine therapy in a phase II trial.
Administered oral sunitinib at 50 mg daily on a 4-weeks-on, 2-weeks-off schedule.
Collected predose plasma samples on days 1 and 28 of each cycle to quantify VEGF, sVEGFR-2, sVEGFR-3, and PlGF via ELISA.
At cycle 1 completion, VEGF increased >3-fold in 44% (24/54) of patients and PlGF increased >3-fold in 40% (22/55) (P < 0.001), while sVEGFR-2 fell ≥30% in 91% (50/55) (P < 0.001) and sVEGFR-3 fell ≥30% in 87% (48/55).
Circulating protein concentrations returned toward baseline during the 2-week off-treatment interval, showing exposure dependence.
Patients with objective tumor response exhibited significantly greater shifts in VEGF, sVEGFR-2, and sVEGFR-3 compared to those with stable or progressive disease (P < 0.05 for each analyte).

Cite This Study

DePrimo et al. (2007) studied this question.

synapsesocial.com/papers/6a7cef3f14f353e48e91b0fd https://doi.org/10.1186/1479-5876-5-32

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Implication

Phase II trial reveals modulation of circulating VEGF-related proteins by sunitinib in metastatic renal cell carcinoma, indicating their utility as dynamic biomarkers of drug activity.

Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins

Discussion

Member takes

Implication

Key Points

Cite This Study

Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins

Discussion

Member takes

Implication

Key Points

Cite This Study

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