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Anti-Angiogenic (Metronomic) Chemotherapy in Children with Poor Prognosis.

Institution: 
Dana-Farber Cancer Institute
Researcher(s): 
Mark Kieran, MD, PhD
Grant Type: 
Innovation Grants
Year Awarded: 
2006
Type of Childhood Cancer: 
General Pediatric Cancer
Project Description: 

What were you initially studying with your grant funded by ALSF?

The treatment of cancer has been based on the concept that the maximum dose of chemotherapy, while more toxic, is also the most effective way to treat cancer. Over the last decade, a new approach that alters the delivery of chemotherapy into small regular doses that target the tumor microenvironment rather than the tumor cells directly has permitted for much lower, less toxic and better tolerated treatment while showing promising activity. Multiple pre-clinical studies were conducted by our group to evaluate the activity of this approach using different low-dose oral agents and has become commonly referred to as metronomic administration. The goal of the ALSF grant was to conduct a large multi-institutional trial of metronomic therapy in children with progressive/recurrent cancer based on our existing pre-clinical and pilot clinical data.

What have you found?

A phase II multi-institutional trial of metronomic chemotherapy was conducted in 101 patients in 8 different disease stratum to assess the activity of this approach. Since the microenvironment of different tumors can vary significantly, an analysis of different tumors was used to provide the data on which larger disease specific protocols could be tested.

What does this mean for children with cancer and their families?

Current options for children with current/progressive disease are limited. Parents must balance the desire to continue therapies that could slow or stop tumor progression with the recognition that treatments in end stages of cancer cause significant toxicity and limited benefit. Metronomic therapy is a well tolerated oral treatment that can be provided at home, allowing families to continue to treat their children while optimizing their comfort and care.

What are your next steps?

Based on the results of the completed phase II trial of metronomic therapy, activity in certain tumor types has been identified. We have now started a large international phase II trial of this approach for children with recurrent medulloblastoma.

Has this research been published?

The manuscript is under review.

What has this grant allowed you to do that you wouldn’t have been able to do otherwise?

Metronomic therapy uses standard chemotherapy agents at low continuous dosing. As such, most of the drugs are off patent and new dosing regimens are not of interest to the pharmaceutical industry. The ALSF grant, in combination with other avenues of support, allowed this clinical trial to move forward.