St Jude Study on Kid's Bones in Antiangiogenesis Trials

1- Angiogenesis  (can be thought of as new blood vessel formation) is considered to be a key process in the development and growth of glioblastomas.
2- Most DIPGs so far have been found to be glioblastomas.

Given these above two facts,  researchers at St Jude Children Research Hospital in Memphis designed two phase 1 trials using antiangiogenic drugs in during radiation and after for newly diagnosed kids with DIPG tumors.   The first study used vandetanib and the second used a combination of vandetanib and dasatinib.    Both of these drugs are oral and affect targeted areas in the molecular pathways.  Vandetanib is a potent VEGFR-2 (vascular endothelial growth factor receptor-2) inhibitor.

Pediatric patients are not just little adults.   A significant difference is that kids grow and mature.   This could be a problem with antiangiogenesis drugs as animal studies showed that this type of inhibition could negatively affect skeletal growth.    Since little had been reported on the effects of these drugs on children's skeletal development, St Jude researchers included this as part of their study.

There were 59 patients (32 girls and 27 boys) evaluated with a total of 119 MRIs and 51 patients had plain knee x-rays.  The children ranged from 2.4-17.6 years (median 6.2 years of age).  The median treatment was 205 days.   Of note, two patients had not progressed- one was 18 months out from diagnosis and the other 60 months.

All of the kids had MRIs of the knees at baseline and 50 had MRIs at 16-19 weeks of therapy.   MRIs showed more abnormalities than plain films.   MRIs showed:

• 1 patient with premature physeal fusion (the growth plate closed too soon), 
• 1 patient focal thickening of the growth plate,
• 2 patients with bony spicules across the growth plate,
• 8 patients with osteonecrosis (one was present at enrollment in the study).

Plain radiographs did not show these abnormalities.

Although this was a short followup time, this is the largest group of kids studied for skeletal changes on these antiangiogenesis agents.   It seems clear that MRI is better in picking up abnormalities.  The authors encourage more long term follow-up monitoring in pediatric patients taking these agents.

Note- this work was supported in part by US National Institute of Health Cancer Center Suppport (CORE) Grant P30 CA-21765, a Center of Excellence grant from the State of Tennessee, AMerican Lebanese Syrian Associated Charities (ASLAC), Noyes Brain Tumor Foundation, Musicians Against Childhood Cancer (MACC), AstraZeneca and The Cure Starts Now Foundation.

Reference:
Magnetic Resonance Imaging Is the Preferred Method to Assess Treatment-Related Skeletal Changes in Children with Brain Tumors
Pediatr Blood Cancer. 2013 Mar 22. doi: 10.1002/pbc.24536. [Epub ahead of print]
Department of Radiological Sciences, St. Jude Children's Research Hospital
Kaste SC, Kaufman RA, Gajjar A, Broniscer A.
http://www.ncbi.nlm.nih.gov/pubmed/23526749

What is VEGF?   http://www.news-medical.net/health/What-is-VEGF.aspx

St Jude Vandetanib Trials-
http://clinicaltrials.gov/ct2/show/NCT00472017?term=vandetanib+St+Jude&rank=1

http://clinicaltrials.gov/ct2/show/NCT00996723?term=vandetanib+St+Jude&rank=2