Pharmacodynamic analysis of tumour perfusion assessed by 15O-water-PET imaging during treatment with sunitinib malate in patients with advanced malignancies

Patients with advanced malignancies received sunitinib 50？mg/day orally, once daily for 4？weeks on treatment, followed by 2？weeks off treatment, in repeated 6-week cycles. Quantitative measurement of tumour perfusion was assessed using 15O-water-PET at baseline and after 2？weeks of treatment. At least one reference tumour lesion was included in the fields of view and assessed at both time points. Patients also underwent 18？F-fluorodeoxyglucose (FDG)-PET imaging at baseline and after 2 and 4？weeks of treatment. Radiological response of the reference tumour lesion and overall radiological response were assessed at week 12. Serum pharmacokinetic and biomarker analyses were also performed.Data were available for seven patients. Compared with baseline, all patients experienced a decrease in reference tumour blood flow ranging from 20？% to 85？% and also a reduction in the FDG standard uptake value ranging from 29？% to 67？%. Six patients experienced a partial metabolic response based on FDG-PET criteria. Four patients had stable disease defined by radiological response (Response Evaluation Criteria in Solid Tumors) lasting between 4 and 12 cycles. An association between perfusion change and clinical benefit, and biomarker levels including vascular endothelial growth factor was observed.Administering sunitinib to patients with advanced malignancies is associated with early biological responses, including decreased blood flow in secondary tumour deposits.Once solid tumours have reached an advanced or metastatic stage, treatment is largely palliative rather than curative, with the aim of prolonging survival, relieving pain and other symptoms, and maintaining or improving quality of life [1-3]. Pharmacotherapy at such advanced stages is generally targeted at slowing, halting, or - if possible - reversing tumour progression, and at reducing the chance of further metastasis.Targeted biological therapies with antiangiogenic properties may be particularly beneficial in the palliat