A randomised trial of the European and American Osteosarcoma Study group to optimize treatment strategies for resectable osteosarcoma based on the histological response to pre-operative chemotherapy

What is the best treatment for rare bone cancer?

What was this study about?

The aim is to find out how best to treat people with osteosarcoma, a rare form of bone cancer which mainly affects teenagers but also adults and young children. There are only about 150 people diagnosed with osteosarcoma each year in the UK. Therefore the trial is taking place in many different countries to ensure a large enough sample of patients. The purpose of the trial is not to test new drugs, but to see whether existing drugs can be given in a better way. The usual treatment is a combination of three chemotherapy drugs followed by surgery to remove the tumour and then further chemotherapy after surgery. The aim is to see if treatment can be improved by either giving extra chemotherapy drugs after surgery, or by giving a further drug called Interferon after the standard chemotherapy treatment has been given.

The results of the poor responders paper have been published in The Lancet Oncology. The results are summarised in this article and you can find the EURAMOS-1 poor responders participant summary here.

What difference did this study make?


All patients had the chemotherapy drugs, and then surgery. After surgery, doctors assessed whether the patient’s tumour had responded well or poorly to the pre-operative chemotherapy.


"Poor Response Randomisation"

618 patients whose tumour had responded poorly to pre-operative chemotherapy were randomised to receive either:

  • Standard post-operative chemotherapy
  • Standard post-operative chemotherapy plus two extra drugs, ifosfamide and etoposide (MAPIE).

The results showed that adding ifosfamide and etoposide to standard post-operative chemotherapy did not improve how long participants survived without either the disease coming back again or getting worse, or new tumours developing, or dying (event-free survival). Adding ifosfamide and etoposide also increased the numbers of severe side-effects participants had. More people in the MAPIE group have developed a second cancer other than osteosarcoma than in the MAP group. However, the numbers were small (10 on MAPIE compared to 3 on MAP). We cannot yet be sure this difference was caused by the chemotherapy.


"Good Response Randomisation"

716 patients whose tumour responded well to pre-operative chemotherapy were randomised to one of two groups:

  • 359 patients who were allocated to 4 cycles of MAP chemotherapy after their surgery
  • 357 patients who were allocated to 4 cycles of MAP chemotherapy followed by weekly pegylated interferon-α-2b (Peg-Intron) for 74 weeks

Interferon is produced naturally in the body, and has been found to be an effective treatment for some cancers. In EURAMOS-1, interferon was injected under the skin. The average age of people taking part in EURAMOS-1 was 14 years old. The disease had spread to other parts of the body in 12% of those taking part.

The results showed that adding interferon after the standard treatment did not significantly improve the event-free survival. Event free survival was the length of time participants survive without:

  • the disease coming back again
  • the disease getting worse
  • new tumours developing
  • death

The results are complicated because almost quarter of patients randomised to receive interferon did not start taking it, mostly because they chose not to. Furthermore, four in every 10 patients who started interferon stopped early, almost half because of side effects, and a quarter because their disease had worsened. Half of patients on interferon needed to cut the dose of interferon, or delay it, and half of patients who started interferon experienced severe side effects. Most of these side effects were blood problems.

Together this means that the average dose of interferon received by patients randomised to receive it was much lower than planned. This may be why the trial was unable to see a clear benefit from interferon.

The results of EURAMOS-1 do not support adding interferon to the standard treatment for patients with osteosarcoma. They also suggest that, after six months of standard treatment, children and young people who have responded well to chemotherapy are not keen to have weekly injections for another 18 months. Follow-up is continuing, to help us understand the long-term effects of these treatments.


Type of study

Randomised trial

Contact details

Who funded the study?

Europe - ESF (European Science Foundn) (Ref No MM/NG/EMRC/0202); Belgium - FNRS (Fonds National de la Recherche Scientifique); BelgiumFWO (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen; Canada - Children’s Oncology Group; Denmark - Danish Medical Research Council; Finland - Academy of Finland; Germany - DFG ref No: BI 1045/1-1 and 1-2 Germany - DKH ref No: 50-2723-Bi2; Hungary - Semelweis Foundation; Netherlands - ZonMw (Council for Medical Research); Norway - Reseach Council of Norway; Sweden - Scandinavian Sarcoma Group; Switzerland - Swiss Paediatric Oncology Group (SPOG); USA - Children’s Oncology Group

When did it take place?

EURAMOS-1 has updated its target accrual to around 2000 patients. EURAMOS-1 reached its target for registrations at the end of June 2011.

Where did it take place?

Hospitals throughout Europe (including Austria, Belgium, Denmark, Finland, Germany, Hungary, The Netherlands, Sweden, Switzerland and the UK), North America and Canada.

Who was included?

People up to 40 years old who have a high-grade osteosarcoma that can be removed by surgery and that is in a bone in the leg, arm, pelvis, rib, spine or other extremity (but is not in the face or skull).