A Histopathologic and Imaging Study of Renal Cell Carcinoma Vasculature in the Setting of Sunitinib Therapy Prior to Cytoreductive Nephrectomy

OBJECTIVES:

• To correlate histologic measures of tumor angiogenesis and VHL mutation/methylation status with clinical outcome in patients with stage IV renal cell carcinoma treated with sunitinib malate.
• To determine the effects of sunitinib malate on tumor vascular permeability by dynamic contrast-enhanced MRI and iodine I 124 chimeric monoclonal antibody G250 positron emission tomography (PET) after 2 weeks of therapy.
• To correlate steady-state plasma concentrations of sunitinib malate and angiogenic growth factors in serum with clinical outcome in these patients.

OUTLINE:

• Neoadjuvant therapy:Patients receive oral sunitinib malate once daily on days 1-14.
• Cytoreductive surgery: Patients undergo cytoreductive nephrectomy on day 16.
• Adjuvant therapy:Beginning at least 4 weeks after surgery, patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity.

Patients undergo dynamic contrast-enhanced MRI with motexafin gadolinium and positron emission tomography with iodine I 124 chimeric monoclonal antibody G250 at baseline and after completion of neoadjuvant sunitinib malate (prior to cytoreductive nephrectomy).