Pharmacodynamic Study Using FLT PET/CT in Patients with Renal Cell Cancer and Other Solid Malignancies Treated with Sunitinib Malate
Liu, G. ...
Purpose : To characterize proliferative changes in tumors during the sunitinib malate exposurežwithdrawal using 3ć-Deoxy-3ć-š18Fđfluorothymidine (FLT) PETžCTimaging. Patients and MethodsČ Patients ...with advanced solid malignanciesand no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PETžCT imaging. Sunitinib was initiated at the standard dose of 50 mg PO daily either on a 4ž2 or 2ž1 schedule. FLT PETžCT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic data were assessed at the same time points. ResultsČ 16 patients (8 pts on 4ž2 scheduleč 8 pts on 2ž1 schedule) completed all three planned FLT PETžCT scans, and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scan 2 to 3), median FLT PET SUVmean increased +15% (range -14% to +277%) (p=0.047) for the 4ž2 schedule and +19% (range -5.3% to +200%) (p=0.047) for the 2ž1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure, and returned towards baseline during the treatment withdrawal. ConclusionsČ The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGFR TKI withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early Ćangiogenic escape.
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