Biomarkers Allow Doctors To Match Therapy To Patient

Researchers have identified two potential biomarkers that could help doctors monitor the effectiveness of treatment with sunitinib or bevacizumab for kidney and non-small cell lung cancer.

"Our work provides novel data on a potential biomarker for the monitoring of anti-angiogenic drug activity in cancer patients, as well as identifies a cell type that is a potential target for these agents," said Laura Vroling, M.Sc., a researcher in the Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.

The vascular endothelial growth factor (VEGF) receptor targeted agents bevacizumab and sunitinib have proven effective against several cancers, such as non-small cell lung cancer, colorectal and kidney cancer, but it is unclear which subset of patients will benefit most from these agents, researchers say. "Therefore, it is of great importance to identify and validate biomarkers for early response or duration of response," Vroling said.

Vroling and colleagues studied therapy-induced changes in a novel, rare, circulating cell population. They measured these candidate circulating endothelial progenitor cells (ccEPCs) characterized by the markers CD45neg, CD34bright and CD133neg during sunitinib or bevacizumab treatment.

They labeled them "candidate" cells because no data have proven definitively the phenotypic relationship between progenitor and blood-derived endothelial outgrowth cells, Vroling said.

Their study included 23 patients with renal cell cancer and 19 patients with non-small cell lung cancer. The researchers also monitored plasma levels of VEGF. They assessed tumor response with computed tomography scans according to the RECIST criteria.

"This is the first study to assess the kinetics of ccEPCs together with other circulating cells in the peripheral blood of patients with renal cell cancer during the first cycle of sunitinib treatment," Vroling said.

During a four-week "on" period of treatment with sunitinib, the ccEPC increases paralleled the rise in plasma VEGF levels; they decreased during the two-week "off" period, Vroling reports. Monocytes and hematopoietic progenitor cells (HPCs) demonstrated the opposite pattern, according to Vroling.

"In a preliminary analysis, we found a significant difference in the change of ccEPC numbers and VEGF levels after two weeks of treatment between patients with clinical benefit and progressive disease," Vroling said. "We also noted that an increase of ccEPCs was indicative of a longer progression-free survival in this small group of patients."

In the patients with non-small cell lung cancer treated with bevacizumab and erlotinib, ccEPC levels increased, while free plasma VEGF levels decreased. ccEPCs did not rise in a control group treated with erlotinib alone, Vroling said.

"These data suggest that ccEPCs are increased in cancer patients in an anti-angiogenic, treatment-specific way," she said. Furthermore, this effect does not seem to be related to plasma VEGF levels.

"In our study for the first time the behavior of two CD34bright cell populations, (CD45neg) candidate cEPCs and (CD45dim) HPCs were monitored and showed a different response of both cell populations during sunitinib or bevacizumab therapy. The role of ccEPCs in human tumor angiogenesis and their potential in prediction of treatment outcome of anti-VEGF therapy needs to be addressed in future, larger clinical cohorts," she said.

This research was presented at the American Association for Cancer Research 2008 Annual Meeting, April 12-16.