gms | German Medical Science

Osteosarcoma was the model tumor when the principles of preoperative “neoadjuvant” induction chemotherapy were first developed. Most recent trials have evaluated varying combinations of two or more of the same four drugs: doxorubicin, high-dose methotrexate, cisplatin, and ifosfamide. Several independent clinical prognostic factors could be defined, including tumor site and size, the presence or absence of primary metastases, tumor response to preoperative chemotherapy, and the extent of surgical resection. Limb-salvage has been shown to be a safe procedure, provided surgical margins are wide and the tumor is responsive to chemotherapy. Despite repeated attempts at defining the optimal number and combination(s) of cytostatic agents, however, these issues are far from having been solved. Also, the high hopes which were at first associated with the concept of salvage chemotherapy – changing postoperative treatment for poor responders to induction chemotherapy - have so far not been fulfilled. Overall, in Europe as well as elsewhere, the past two decades saw only moderate gains, with survival rates for patients with localized extremity tumors hovering at 50-70%. Due to the rarity of the disease and the moderate amount of progress which can currently be expected unless totally new therapeutic approaches become available, even the largest multinational collaborative groups need many years to accrue sufficient patient numbers for their prospective trials. Therefore, European and American investigators representing four renowned multicentric trial groups (COG, COSS, EOI, SSG) have joined forces in the European and American Osteosarcoma Study Group (EURAMOS), a transatlantic attempt to define the optimal first-line protocol for children, adolescents, and young adults with osteosarcoma. The first randomized trial, EURAMOS-1, performed in 12 European countries, the USA, and Canada has started recruiting patients in 2005. It evaluates salvage therapy with high-dose ifosfamide and etoposide for poor responders and maintenance treatment with interferon alfa in others. EU-Directive 2001/20 and its very heterogenous interpretation and implementation status in the participating European countries provided multiple formidable challenges, with a strong impact on workload, financial requirements, and the timeliness of opening the trial. Another current European intergroup project – the European Bone Over 40 Sarcoma Study EURO-B.O.S.S. - is aimed at patients aged 41-65 years with osteosarcomas and other spindle cell sarcomas of bone, which have so far been neglected by most protocols. Provided that these efforts are successful, osteosarcoma may again serve as a model, this time for truly Pan-European and even transatlantic cooperation in the fight against rare malignancies.