The most active chemotherapeutic agents for osteosarcoma are doxorubicin10-11, cisplatin12-14, and methotrexate 15-17. In recent years ifosfamide18-20 usually in combination with etoposide 20-21 has also shown activity in this disease.
Currently, an intergroup trial, the European and American Osteosarcoma Study (EURAMOS-1), is being undertaken by several European and North American study groups [the North American Children’s Oncology Group (COG), the German-Austrian-Swiss Cooperative Osteosarcoma Study Group (COSS), the European Osteosarcoma Intergroup (EOI) and the Scandinavian Sarcoma Group (SSG)]. EURAMOS-1 is a phase III, open label, randomized controlled clinical trial of parallel groups with the intention to optimize therapy for patients with osteosarcoma.
The aim of EURAMOS-1 is to investigate whether it is feasible to improve outcome for both good and poor responders through the addition of extra agents into the post-operative treatment schedule.
All patients will receive 10 weeks of chemotherapy with MAP (Methotrexate, doxorubicin (Adriamycin) and cisPlatin), followed by surgery to remove the primary tumour. Poor responders (>10% viable tumour) will be randomised between MAP for 18 weeks and the MAPIE (methotrexate, doxorubicin, cisplatin, ifosfamide and etoposide) regime for 29 weeks. Good responders (<10% viable tumour) will be randomised between MAP for 18 weeks and MAPinf, consisting of MAP for 18 weeks followed by maintenance therapy with interferon-a, which is continued for up to 2 years from diagnosis.
The rationale for using interferon-a comes from in vitro and in vivo studies demonstrating its inhibitory effects on osteosarcoma cell lines and animal models22-24, in addition to a single study of 64 patients with osteosarcoma in which adjuvant interferon-a following surgery apparently increased relapse free survival25-27 .