• Age <40 years
• Previously untreated patients with non-metastatic high grade osteosarcoma of the extremities.
• Eligible patients must have a morphologically confirmed diagnosis of highly malignant osteosarcoma.
• No regional or distant metastatic disease, determined by:
  -Physical examination
  -Chest x-ray
  -Chest scan
  -Total body bone scan
• Adequate bone marrow function.
• Start of chemotherapy within 2 weeks after biopsy
• After pre-operative chemotherapy the surgical margin must be wide or compartmental.

Preoperative treatment
2 cycles
Methotrexate: 12 g/m2, day 1, 8
Adriamycin: 25 mg/m2, day 15, 16, 17
Cisplatin: 90 mg/m2, day 15
Surgery week 9

Postoperative treatment - Tumor response grade I-II
5 cycles
Ifosfamide: 1.5 g/m2,  day 1-3
Mitexan: 600 mg x 3 i.v. inj. day 1-3
VP-16: 600 mg/m2 (72 h. inf.) day 1

Postoperative treatment - Tumor response grade III-IV
3 cycles
Methotrexate: 12 g/m2, day 1, 8
Adriamycin: 25 mg/m2, day 15, 16, 17
Cisplatin: 90 mg/m2, day 15

Secondary
1. To improve the effects of the preoperative treatment on the tumour.

2. To reduce long term toxicity such as impairment of heart function, hearing defects, and hypomagnesemia by shortening the total treatment time and the total accumulated total dose of the cytotoxic drugs.

1990-1998

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Smeland S, Müller C, Alvegard TA, Wiklund T, Wiebe T, Björk O, Stenwig AE, Willén H, Holmström T, Follerås G, Brosjö O, Kivioja A, Jonsson K, Monge O, Saeter G: Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders. Eur J Cancer 2003; Mar 39(4):488-94