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Results summary of St. Jude clinical trial: 

OS2008

 
 

A study of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in combination with chemotherapy for treatment of osteosarcoma (OS2008)

Why was this study done?

Children and adolescents with osteosarcoma, a type of bone cancer, usually undergo surgery and take multiple cancer drugs: methotrexate, doxorubicin (brand name: Adriamycin®) and cisplatin. This standard chemotherapy (chemo) for osteosarcoma is called MAP, formed from letters in the names of the drugs.

Osteosarcoma is the most common cancerous bone tumor in children and teens. The outcome for patients whose disease has not spread has not improved for decades. New therapies are needed.

One strategy targets a substance made by cells called vascular endothelial growth factor (VEGF). VEGF plays a key role in a process called angiogenesis. Angiogenesis is the formation of new blood vessels. This process spurs tumor growth and helps cancer cells spread to other parts of the body. Survival rates are poor for osteosarcoma patients with high levels of VEGF.

The drug bevacizumab can bind to cancer cells and prevent blood vessel formation and tumor growth.

Scientists wanted to know if they could improve survival by combining bevacizumab and MAP to stop angiogenesis.

The study’s main goals were to:

  • find out if the anti-VEGF drug bevacizumab could enhance MAP chemo
  • find out if bevacizumab affects healing after surgery. The natural formation of new blood vessels is important in these patients after surgery

When was this study done?

The study opened in June 2008 and closed to accrual May 2012.

What did the study consist of?

Thirty-one patients received two treatment courses of MAP chemo before and after surgery. They got bevacizumab before starting chemo and at specific times beginning five weeks after surgery. Also, scientists studied how the amount of bevacizumab changed with time within the body.

Clinicians monitored patients for bevacizumab-related side events. In other adult studies side effects included high blood pressure, blood clots, blocked arteries, and higher-than normal amounts of protein in the urine.

What did we learn from this study?

  • Bevacizumab did not enhance standard chemo and improve patient outcomes.
  • Adding bevacizumab to standard chemo did not add significant side effects to treatment. Most side effects from bevacizumab were relatively mild.
  • Bevacizumab increased the risk of wound-healing problems. Problems occurred in about half of the patients after surgery. Twenty-one percent of planned doses of the drug were stopped or skipped.

What are the next research steps as a result of this study?

Bevacizumab will not be combined with MAP in the future for children and adolescents with osteosarcoma. The study provides important data that can be used for future studies of antiangiogenic drugs in treatments that require surgery for bone tumors.

Results of this clinical trial will help clinicians as they evaluate other newer antiangiogenic drugs for future osteosarcoma studies.

How does this study affect my child?

Every childhood cancer survivor should receive long-term follow-up care. Through the St. Jude After Completion of Care clinic, your child will receive information and guidance for care after treatment. Please speak with your St. Jude doctor about specific guidelines that apply to your child.

For more information

Please talk with your child’s doctor about questions or concerns you have as a result of this study.

Publications generated from this study:

A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy. Navid F, Santana VM, Neel M, McCarville MB, Shulkin BL, Wu J, Billups CA, Mao S, Daryani VM, Stewart CF, Kunkel M, Smith W, Ward D, Pappo AS, Bahrami A, Loeb DM, Reikes Willert J, Rao BN, Daw NC. Int J Cancer. 2017 Oct 1;141(7):1469-1477. 
https://www.ncbi.nlm.nih.gov/pubmed/28631382

Population pharmacokinetics of bevacizumab in children with osteosarcoma: implications for dosing. Turner DC, Navid F, Daw NC, Mao S, Wu J, Santana VM, Neel M, Rao B, Willert JR, Loeb DM, Harstead KE, Throm SL, Freeman BB 3rd, Stewart CF. Clin Cancer Res. 2014 May 15;20(10):2783-92. 
https://www.ncbi.nlm.nih.gov/pubmed/24637635