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Treatment

The treatment of osteosarcoma up until 1970s was exclusively surgical. Outcome was poor with a 5 year overall survival rate of 20%⁵. This dismal outlook improved since multi-agent chemotherapy was added to surgery and most recent series report 3 year disease-free survival rates of 60-70% following administration of pre-operative multi-agent chemotherapy, followed by surgical resection and continuation of chemotherapy post-operatively ^6-9.

The most active chemotherapeutic agents for osteosarcoma are doxorubicin^10-11, cisplatin^12-14, and methotrexate ^15-17. In recent years ifosfamide^18-20 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 models^22-24, in addition to a single study of 64 patients with osteosarcoma in which adjuvant interferon-a following surgery apparently increased relapse free survival^25-27 .

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