SAN DIEGO—Dutch researchers say that they have identified potential biomarkers which might help physicians monitor the effectiveness of bevacizumab in non-small-cell lung cancer (NSCLC) patients and in patients with advanced kidney cancer treated with sunitinib.


These agents, which inhibit the vascular endothelial growth factor (VEGF) receptor, have proven effective against several cancers, such as renal cell carcinoma (RCC) and non-small-cell lung and colorectal cancer. It is unclear which subset of patients will benefit most from these agents.

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The researchers studied changes in candidate circulating endothelial progenitor cells (ccEPCs)—characterized by the markers CD45 neg, CD34 bright, and CD133 neg—during sunitinib or bevacizumab treatment. The researchers labeled them “candidate” cells because no data have proven definitively the phenotypic relationship between progenitor and blood-derived endothelial outgrowth cells.


The study included 23 patients with RCC and 19 patients with non-small-cell lung cancer. The investigators monitored plasma levels of VEGF. They assessed tumor response with CT 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,” said lead investigator Laura Vroling, MSc, a researcher in the department of medical oncology at the VU University Medical Center in Amsterdam, The Netherlands.


“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. We also noted that an increase of ccEPCs was indicative of a longer progression-free survival in this small group of patients.”


During a four-week “on” period of treatment with sunitinib, the ccEPC increases paralleled the rise in plasma VEGF levels and then decreased during the two-week “off” period, according to Vroling. Mono-cytes and hematopoietic progenitor cells (HPCs) demonstrated the opposite pattern.


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


“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,” Vroling explained. “The role of ccEPCs in hu-man tumor angiogenesis and their potential in prediction of treatment outcome of anti-VEGF therapy needs to be addressed in future, larger clinical cohorts.”


Nephrologists may be especially interested in these findings be-cause identifying these types of

biomarkers may lead to lower morbidity and mortality rates among patients with renal cell carcinoma, Vroling noted.


She reported findings here at the American Association for Cancer Research annual meeting.