Doctors at St. Jude Children's Research Hospital in Memphis recognized that blood vessels grown by cancer cells are weak, leaky vessels. These leaks actually create pressure around the cancer cell that becomes protective by preventing penetration of anti-cancer drugs.

In experiments with mice, doctors treated neuroblastoma in the animals with bevacizumab (Avastin), an agent that stops blood vessel growth. That treatment eliminated the faulty blood vessels, leaving strong, normal blood vessels. Then the potent cancer killer topotecan (Hycamtin) was administered.

When the researchers administered topotecan to the tumor-bearing mice three days after bevacizumab, the size of the tumors was only 36 percent of the size of untreated tumors, compared with 88 percent when mice were treated with bevacizumab alone; 54 percent when treated with topotecan alone; and 44 percent when tumor-bearing mice were treated with both drugs at the same time.

Andrew Davidoff, director of surgical research at St. Jude and senior author of a report in the current issue of Clinical Cancer Research, said the research will help doctors create a timetable for using the one-two punch in neuroblastoma, a common childhood cancer.

"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.

"This suggested that 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."