Temporary Improvement Of Tumor Blood Flow Can Improve Chemotherapy

Tumor Blood Flow

Results of neuroblastoma study hold promise for improving treatment by delaying topotecan therapy until after administration of drug that eliminates immature blood vessels in tumor.

A treatment for neuroblastoma that lands a one-two punch works best when the second punch is timed to take maximum advantage of the first one.

Neuroblastoma is a pediatric solid tumor that arises from cells in the peripheral nervous system.

The finding holds promise for improving neuroblastoma treatment by using the drug bevacizumab to block VEGF, a protein that stimulates blood vessel growth in tumors and then following with the chemotherapy drug topotecan, which depends on blood vessels to penetrate the tumor and kill the cancer cells. A report on this work appears in the current issue of "Clinical Cancer Research."

Results of the study are important because drugs such as bevacizumab are being evaluated in clinical trials for children with neuroblastoma. However, there are no standard guidelines for how much of the drug to give or when to give it. Such guidelines would be especially helpful for developing combination therapy with both bevacizumab and chemotherapy drugs, not only for neuroblastoma, but also for other tumors.

"The results of our study are a significant step toward establishing such guidelines," said Andrew Davidoff, M.D., director of surgical research at St. Jude, and the report's senior author.

The St. Jude team based their strategy on previous findings that suggested blocking VEGF at first improves the tumor's vasculature, or blood vessel system, by eliminating weak and faulty vessels, while temporarily sparing healthy, normal blood vessels.

"We observed in the mouse model of neuroblastoma that the maximum amount of topotecan reached the tumor and had maximum tumor-reducing effect if we waited three days after administering bevacizumab," Davidoff said. "Combination treatment of children with neuroblastoma should take into account that there is a window of opportunity for improving topotecan delivery after treatment with bevacizumab. Further studies should tell us how long that window is open."