• Age <40 years
• Untreated patients with non-metastatic high-grade osteosarcoma
• Histologically confirmed diagnosis of highly malignant osteosarcoma
• No regional or distant metastatic didease
• An absolute leukocyte count not less than 3x109/L and an absolute trombocyte count not less than 100x109/L, initially
• Start of chemotherapy as soon possible after incisional biopsy of the lesion
• After pre-operative chemotherapy the surgery must be macro- and microscopally radical.

Induction chemotherapy
<8 year
HDMTX:12 g/m2, day 1, 8, 15, 21
Surgery: day 28
Bleomycin: 15 mg/m2, day 42, 43
Cyclophosphamide: 600 mg/m2, day 42, 43
Actinomycin D: 0,6 mg/m2, day 42, 43
HDMTX: day 63
Adriamycin: 30 mg/m2, day 70, 71, 72
HDMTX: week 14
Surgery: week 16

>8 year
HDMTX: 8 g/m2, day 1, 8, 15, 21
Surgery: day 28
Bleomycin: 15 mg/m2, day 42, 43
Cyclophosphamide: 600 mg/m2, day 42, 43
Actinomycin D: 0,6 mg/m2, day 42, 43
HDMTX: day 63, 70
Adriamycin: 30 mg/m2, day 77, 78, 79
HDMTX: week 14, 15
Surgery: week 16s

Response Grade I-II
Adriamycin: 30 mg/m2, day 1, 2, 21, 22
Cisplatin: 120 mg/m2, day 1, 21
Bleomycin: 15 mg/m2, day 42, 43
Cyclophosphamide: 600 mg/m2, day 42, 43
Actinomycin D: 0,6 mg/m2, day 42, 43
Cycle length: 63 days
Total 3 cycles

Response Grade III-IV, <8 year
Bleomycin: 15 mg/m2, day 1, 2
Cyclophosphamide: 600 mg/m2, day 1, 2
Actinomycin D: 0,6 mg/m2, day 1, 2
HDMTX: 12 g/m2, day 21, 56
Adriamycin: 30 mg/m2, day 28, 29, 30
Cycle length: 70 days
Total 3 cycles

Response Grade III-IV, >8 year
Bleomycin: 15 mg/m2, day 1, 2
Cyclophosphamide: 600 mg/m2, day 1, 2
Actinomycin D: 0,6 mg/m2, day 1, 2
HDMTX: 8 g/m2, day 21, 28, 56, 63
Adriamycin: 30 mg/m2, day 35, 36, 37
Cycle length: 70 days
Total 3 cycles (No MTX in the last cycle)

1. Disease-free survival
2. Overall survival

Solheim Ø, Alvegård T A, Elomaa I: Adjuvant chemotherapy for osteosarcoma a preliminary report from the Scandinavian Sarcoma Group. Acta Oncol 1989;(Suppl 2)28:53-7.

Saeter G, Alvegård TA, Elomaa I, Stenwig AE, Holmström T, Solheim OP: Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate. A Scandinavian Sarcoma Group study. J Clin Oncol1991;9:1766-75.

Solheim OP, Saeter G, Elomaa I, Alvegård TA: The treatment of osteosarcoma: present trends. The Scandinavian Sarcoma Group experience. Ann Oncol. 1992;(Suppl 2):3:711.