Magnetic Resonance Imaging–Measured Blood Flow Change after Antiangiogenic Therapy with PTK787/ZK 222584 Correlates with Clinical Outcome in Metastatic Renal Cell Carcinoma

• Published in: Clinical cancer research Vol. 14; no. 17; pp. 5548 - 5554
• Main Authors: de Bazelaire, Cedric, Alsop, David C, George, Daniel, Pedrosa, Ivan, Wang, Yongyu, Michaelson, M Dror, Rofsky, Neil M
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-09-2008
• Subjects: Angiogenesis Inhibitors - therapeutic use; Carcinoma, Renal Cell - blood supply; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Disease Progression; Feasibility Studies; Humans; Kidney Neoplasms - blood supply; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Magnetic Resonance Imaging - methods; Neoplasm Metastasis; Neovascularization, Pathologic - drug therapy; Phthalazines - therapeutic use; Pyridines - therapeutic use; Regional Blood Flow - drug effects
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0417

Purpose: To measure changes in tumor blood flow following treatment with PTK787/ZK 222584, a pan–vascular endothelial growth factor
receptor tyrosine kinase inhibitor, and their association with clinical response in patients with metastatic renal cell carcinoma.
Experimental Design: In 10 patients with metastatic renal cell carcinoma treated with PTK787/ZK 222584, tumor blood flow was evaluated by arterial
spin labeling (ASL) magnetic resonance imaging before and 1 month on treatment. Changes in blood flow after 1 month of treatment
were compared with bidimensional tumor response at 4 months of treatment using the Mann-Whitney test.
Results: Changes in blood flow at 1 month and changes in tumor size measured at 4 months or at time of disease progression were significantly
correlated ( P = 0.01). Patients with progressive disease within 4 months on treatment ( n = 4) had a nonsignificant increase in tumor blood flow at 1 month (+25 ± 33%; P = 0.43), whereas patients with stable disease or partial response at 4 months ( n = 6) had a significant decrease in tumor blood flow at 1 month (−42 ± 22%; P = 0.02).
Conclusion: These results suggest that decreasing tumor blood flow with PTK787/ZK 222584 therapy, as shown as soon as 1 month on therapy
by ASL, may predict for a favorable clinical outcome. These data are consistent with a hypothetical functional role for tumor
ischemia in the mechanism of response to anti–vascular endothelial growth factor therapy. ASL blood flow magnetic resonance
imaging shows promise as an early predictor of clinical response to antiangiogenic therapies.