Osteosarcoma: the European Osteosarcoma Intergroup (EOI) perspective.

In the late 1970s, there was confusion regarding the best management for osteosarcoma. The benefit of chemotherapy had not been established and which chemotherapy could be used was even more uncertain. The European Osteosarcoma Intergroup (EOI) was established in order to conduct randomised studies to determine the best treatment for this tumour. Their first study 80831 established that a two drug combination of CDDP/DOX was safe and improved the survival rate over previous regimes with suboptimal chemotherapy. The CDDP/DOX was superior to a less intense CDDP/DOX/MTX regime. The second study 80861 compared the CDDP/DOX arm with a multi-drug Rosen-T10 regime. In almost 400 patients, there was the difference in outcome between the two arms. However, adherence to the protocol and completion of allocated treatment was substantially less good in the prolonged 42 week multi-drug regime compared to the two drug arm. The third study 80961 investigated interval compression i.e. if the CDDP/DOX when given every 2 weeks with GCSF superior to the same two drugs given every 3 weeks. There was no difference in survival between the arms, although there was a better histologic response rate in the compressed arm. Three randomised controlled trials on this rare disease have taken more than 20 years to accrue a sufficient sample of patients. The overall outcome has changed little in this time. Large multinational studies are needed to be able to answer these important questions in a timely fashion.