Italian Sarcoma Group (ISG) and Scandinavian Sarcoma Group (SSG)

• Age <40 years.
• Histologically proven osteosarcoma of high malignancy grade (grade III or IV), with primary tumor localization in the pelvis or with metastases at initial presentation irrespective of primary tumor localization.
• The diagnosis must be made by open or coarse needle biopsy.
• Tumor origin should be in the marrow or on the bone surface.
• No previous treatment given for osteosarcoma.
• Adequate bone marrow,  hepatic and renal function.
• Chemotherapy must be started within four weeks from the histological diagnosis.
• The patient registration form must be accompanied by representative histology slides (for verification of diagnosis) and conventional front and lateral x–rays of the entire involved bone (for estimation of tumor volume).

Preoperative
Methotrexate: 12 000 mg/m2 day 1, week 0 and 6
Cisplatin: 60 mg/m2/24 h as 48 h cont. i.v. inf., 2 days week 1 and 7
Adriamycin: 75 mg/m2 as 24 h cont. i.v. inf., day 1, week 1 and 27
Ifosfamide: 3000 mg/m2/24 h as 120 h cont. i.v.inf., 5 days, week 4 and 10
PBSC-harvest: between week 5 and 6
Primary tumor surgery + metastasectomy: week 13

Postoperative
Adriamycin: 90 mg/m2 as 24 h cont. i.v. inf., week 15 and 21
Cyclofosfamide: 4000 mg/m2, day 1 week 18
Etoposide: 200 mg/m2/day, 3 days week 18
PBSC-harvest if necessary: between week 19 and 20
HDEC = Etoposide 450 mg/m2/day, 4 days and Carboplatin 375 mg/m2/day, 4 days week 24 and 28
Peripheral blood stem cell (PBSC) rescue, week 24 and 28 at 72 hours after termination of chemotherapy.

1. In all patients with detectable metastases at initial presentation, to increase 5–year overall survival from 20% to 40%.
2. In patients who undergo complete metastasectomy, to increase 5–year overall survival from 40% to 60%.
3. In patients with operable pelvic osteosarcomas, to increase 5–year overall survival from approx. 30% to a level approaching that of extremity tumors (60%), and to increase local control from <50% to 80%.

Secondary

1. To evaluate the prognostic importance of histologic response to preoperative chemotherapy in the primary tumor and metastatic lesions.
2. To evaluate whether patients who remain inoperable after the initial 6 chemotherapy courses can be converted to operability by high–dose chemotherapy with PBSC.

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Under preparation