The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years.