EURAMOS I : Objectives
- In a randomized trial, to examine whether the addition of ifosfamide and etoposide (IE) to post-operative chemotherapy with cisplatin, doxorubicin and methotrexate improves event-free survival for patients with resectable osteosarcoma and a poor histological response to 10 weeks of pre-operative chemotherapy.
- In a randomized trial, to examine whether the addition of interferon-a (ifn) as maintenance therapy after post-operative chemotherapy with cisplatin, doxorubicin and methotrexate improves event-free survival for patients with resectable osteosarcoma and a good histological response to 10 weeks of pre-operative chemotherapy.
- To investigate whether the addition of IE to post-operative therapy for poor responders, and the addition of ifn as maintenance therapy for good responders, leads to an improvement in the following outcomes:
Quality of life
- To investigate whether the addition of IE to post-operative therapy for poor responders, and the addition of ifn as maintenance therapy for good responders, leads to an improvement in event-free and overall survival in patients with localized osteosarcoma at entry.
- To investigate whether biological or clinical correlates to histological response and outcome can be identified.
- To establish whether this international cooperation in clinical trials for osteosarcoma is feasible.
- To examine the outcome of the entire cohort of patients.
Registration eligibility criteria
- Histological evidence of high grade osteosarcoma of the extremity or axial skeleton including those arising as second malignancies
- Resectable disease (defined as disease that is amenable or may become amenable to complete and potentially curative resection. Referral to a recognized specialist center may be appropriate)
- Age < 40 years at date of diagnostic biopsy
- Registration within 30 days of diagnostic biopsy
- Start chemotherapy within 30 days of diagnostic biopsy
- Neutrophils > 1.5 x 109/L (or WBC > 3 x 109/L if neutrophils are not available) and platelet count > 100 x 109/L
- Glomerular Filtration Rate > 70 mL/min/1.73 m2
- Serum bilirubin < 1.5 x ULN
- Sufficient cardiac function to receive anthracyclines: SF > 28% or EF > 50%
- Adequate performance status (Karnofsky score > 60 or WHO < 2 for patients (age > 16), Lansky score > 60 (age < 16). Patients whose performance status is adversely affected by a pathologic fracture but who are able to undergo treatment are eligible (see Appendix A.2 for details)
- Patient fit to undergo protocol treatment and follow-up
- Written informed consent
- Unresectable disease, primary or metastatic or both
- Low grade osteosarcoma
- Juxtacortical (periosteal, parosteal) osteosarcoma
- Craniofacial osteosarcoma
- Any previous treatment for osteosarcoma
- Any previous chemotherapy for any disease
- Any other medical condition precluding treatment with protocol chemotherapy
- Pregnant or lactating women
- Assessment of histological response in primary tumor within 35 days of definitive surgery
- Two courses of cisplatin and doxorubicin administered before surgery
- Between two and six courses of methotrexate administered before surgery
- No severe toxicity precluding post-operative treatment
- No progression of metastatic disease or new metastatic disease
- Macroscopically complete surgical resection of the primary tumor
- In patients with metastatic disease, complete removal of all metastases or complete removal planned and deemed feasible
- Essential data collection will be provided
- Written consent to undergo randomization