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Clin Cancer Res. 2008 Sep 1;14(17):5548-54. doi: 10.1158/1078-0432.CCR-08-0417.

Magnetic resonance imaging-measured blood flow change after antiangiogenic therapy with PTK787/ZK 222584 correlates with clinical outcome in metastatic renal cell carcinoma.

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  • 1Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Abstract

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.

PMID:
18765547
[PubMed - indexed for MEDLINE]
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