A trial looking at treatment for the Ewing sarcoma family of tumours (EURO-EWING 99)

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Cancer type:

Children's cancers
Ewing's sarcoma
Sarcoma

Status:

Results

Phase:

Phase 3

This trial looked at chemotherapy, surgery and radiotherapy for the Ewing sarcoma family of tumours. It was for children, young people and adults up to the age of 50. This trial was supported by Cancer Research UK.

More about this trial

The Ewing sarcoma family of tumours Open a glossary item are a group of cancers that includes Ewing's sarcoma and peripheral primitive neuroectodermal tumour (peripheral PNET). They can develop in the bone or soft tissue, and are often treated the same way. They mostly affect children, teenagers and young adults.  
 
When this trial was done, doctors usually treated Ewing sarcoma family of tumours with chemotherapy and then surgery, radiotherapy or more chemotherapy.
 
This trial compared different combinations of chemotherapy drugs. And looked at how well radiotherapy works for some patients.
 
The main aims of the trial were to find out:
  • which treatments work best for Ewing sarcoma family of tumours
  • more about the side effects
 

Summary of results

The trial team found that:
This trial was open for people to join between 2000 and 2015. 
 
The research team have looked at the different parts of this trial separately:
  • in 2014 they published results comparing VAC and VAI chemotherapy
  • in 2016 they published results about how well radiotherapy worked
  • in 2018 they published results comparing VAI and BuMel chemotherapy
We have information about all of these below.
 
About this trial
Everyone taking part in this trial had chemotherapy to begin with. They then had an operation to remove as much of the cancer as possible, and more chemotherapy.
 
The treatment they had after this depended on how big their cancer was and how well the treatment so far had worked.
 
People whose treatment had worked well were put into 1 of these 2 chemotherapy treatment groups at random:
When this trial was done, doctors often used VAI. The research team wanted to see if it would be ok to use VAC instead.
 
People whose treatment so far had worked less well were put into 1 of these two chemotherapy treatment groups at random:
When this trial was done, doctors often used VAI. The research team wanted to see if BuMel worked better than VAI.
 
Some people also had radiotherapy after their operation, depending on their situation.
 
Results
 
VAC or VAI chemotherapy
The research team looked at 856 people whose initial treatment had worked well. They were put into 1 of 2 groups at random:
  • 431 had vincristine, dactinomycin and cyclophosphamide (VAC)
  • 425 had vincristine, dactinomycin and ifosfamide (VAI)
The team looked at how many people’s cancer had come back or spread to another part of the body 3 years after treatment. They found it was similar in both groups:
  • 114 out of 431 (26%) who had VAC
  • 102 out of 425 (24%) who had VAI
They also looked at how many people had died 3 years after treatment, and found it was the same in both groups:
  • 88 out of 431 people (20%) who’d had VAC
  • 83 out of 425 people (20%) who’d had VAI
Side effects of VAC and VAI
The number of people who had side effects was different for some things:
  • more people who had VAC chemotherapy had a drop in white blood cells and blood clotting cells (platelets)
  • more people who had VAI had problems with kidney function
  • the risk of infection was similar in the two groups
Conclusions about VAC and VAI
The research team concluded that it may be ok to use cyclophosphamide instead of ifosfamide as part of chemotherapy treatment for Ewing sarcoma family of tumours. They suggest more work is done to be sure, and that they monitor long term side effects.
 
Radiotherapy
The research team looked at 599 people who’d had surgery after chemotherapy. Of these:
  • 142 had radiotherapy
  • 457 didn’t have radiotherapy
They looked at how many people’s cancer had come back in the same part of the body. This is called local relapse. It was:
  • 13 out of 142 people (9%) who’d had radiotherapy
  • 54 out of 457 people (12%) who hadn’t had radiotherapy
Sometimes sarcomas are partly, or completely, made up of dying tissue. This is called necrosis. The research team found that radiotherapy worked better for people whose cancer had complete necrosis. When they looked at how many of these people had a local relapse, it was:
  • 1 out of 65 people (2%) who’d had radiotherapy
  • 35 out of 299 people (12%) who hadn’t had radiotherapy
They also looked at how many people’s cancer had spread to another part of the body and how many people had died. They found there wasn’t much difference between the two groups. 
 
Conclusion about radiotherapy
The research team concluded that radiotherapy seems to help stop these cancers coming back in the same area. They recommend people have radiotherapy if they have chemotherapy and surgery but the surgeon was not able to remove all of the cancer. They suggest more trials are done to look at this in more detail.
 
VAI or BuMel chemotherapy
The research team looked at the results for 240 people whose initial treatment had worked less well than they’d hoped. They were put into 1 of 2 groups at random:
  • 118 had vincristine, dactinomycin and ifosfamide (VAI)
  • 122 had busulfan and melphalan (BuMel)
The research team looked at how many people’s cancer had come back 3 years after treatment, and found it was:
  • 60 out of 118 people (51%) who’d had VAI
  • 45 out of 122 people (37%) who’d had BuMel
And when they looked at how many people had died, they found it was:
  • 53 out of 118 people (45%) who’d had VAI
  • 37 out of 122 people (30%) who’d had BuMel
Side effects of VAC and BuMel
More people who had BuMel had side effects than those who had VAI. Some side effects were mild or didn’t last long. But some were classed as severe. More people who had BuMel had severe side effects.
 
The most common side effects were:
  • those that affected the digestive system, such as sore mouth, diarrhoea and being sick
  • changes in liver proteins (enzymes)
  • a drop in red blood cells, white blood cells and clotting cells (platelets)
Conclusions about VAI and BuMel
The research team concluded that BuMel worked better for people whose initial treatment had worked less well, but it did cause more side effects. They recommend people think about making it part of standard treatment for this group of patients.
 
Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in medical journals. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Bernadette Brennan

Supported by

Cancer Research UK
Cancer Research UK Children's Cancer Trials Team
University of Birmingham
European Organisation for Research and Treatment of Cancer (EORTC)
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer

Other information

This is Cancer Research UK trial number CRUK/02/014.

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Freephone 0808 800 4040

Last review date

CRUK internal database number:

278

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

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