Osteosarcoma and Other Cancer of Bone 199
38. Osteosarcoma and Other Cancer of Bone
38.1 General considerations
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Stage grouping (AJCC), TNM classification and grading of osteosarcomas |
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Stage T N M grade* |
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IA T1 N0 M0 G 1, 2 |
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IB T2 N0 M0 G 1, 2 |
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IIA T1 N0 M0 G 3, 4 |
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IIB T2 N0 M0 G 3, 4 |
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III not defined |
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IVA any T N1 M0 G 1-4 |
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IVB any T any N M1 G 1-4 |
* G 1 = well differentialted G2 = moderately differentiated
G 3 = Poorly differentiated G4 = undifferentiated
Low-grade (stage IA/B) osteosarcomas are typically treated with surgery. Therapy of high grade osteosarcomas is based on a multimodality approach of presurgical ( neoadjuvant) multiagent chemotherapy, followed by surgical ablation (nowadays most patients are candidates for limb preservation ) and risk-adapted postoperative (adjuvant) chemotherapy. In patients for whom complete surgical excision is impossible, the addition of radiation therapy may allow for local control.
Malignant fibrous histiocytoma of bone should be treated with aggressive
chemotherapy regimens similar to those for osteosarcomas.
Literature: for review e.g.
BACCI and LARI, J. Chemother. 13 (2001): 235 243
BRAMWELL, Curr. Opin. Oncol. 12 (2000): 330 336
FERGUSON and GOORIN, Cancer Invest. 19 (2001): 292 315
38.2 Osteosarcoma
38.2.1 COSS 86/96 *
Surgery
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A M M I+P I+P A M M I+P M M A M M I+P M M A |
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1. 3. 4. 5. 8. 11. 13. 14. 15. 18. 19. 20. 22. 23. 24. 27. 28. 29. |
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Week |
* Study COSS-96 continues with the concept of COSS-86 with few modifications
A
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Doxorubicin 90 mg/ m2 i.v. (48 h inf) d 1+2 |
(Max cumulative dose 360 mg/m2)
200 Osteosarcoma and Other Cancers of Bone
M
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Methotrexate 12000 mg/m2 i.v. ( 4 h inf) d 1 or (max 20000 mg) 8000 mg/m2 for patients > 25 years |
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Folinic acid 15 mg p.o. every 6 h 24 h after start of MTX until MTX levels < 7 x 10-8 M |
I + P
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Ifosfamide 3000 mg/m2 i.v. ( 1 h inf) d 1 + 2 With mesna uroprotection |
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Cisplatin 120 mg /m2 i.v.(27 h inf) d 3-5 |
Literature:
FUCHS et al, Ann. Oncol. 9 (1998): 893 899
WINKLER et al, Cancer Treat. Res. 62(1993): 269 277
38.2.2 T10 (memorial Sloan- Kettering) and variations
Preoperative
Methotrexate
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Methotrexate 8000 mg/m2* i.v. wks 0, 1, 4, 5 with 1200 mg/m2 ** folinic acid rescue |
* Age > 12 ** Age ≤ 12
BCD
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Bleomycin * 15 mg/m2 i.v. d 1 + 2 |
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Cyclophosphamide 600 mg /m2 i.v. d 1+ 2 |
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Dactinomycin 0.6 mg/m2 i.v. d 1 + 2 |
Week 6 followed by surgery at week 6
* Not in patients with significant decrease in pulmonary function
Postoperative
Grade III/V necrosis (good histologic response)
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Doxorubicin 25 mg/m2 i.v. (cont inf) d 1 - 3 |
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Methotrexate 8000 mg /m2 i.v. wks 11, 14, 18, 21 12000 mg/m2 25, 28, 32, 35 with folinic acid rescue |
* Age > 12 ** Age ≤ 12
BCD
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Bleomycin * 15 mg/m2 i.v. d 1 + 2 |
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Cyclophosphamide 600 mg /m2 i.v. d 1+ 2 |
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Dactinomycin 0.6 mg/m2 i.v. d 1 + 2 |
Weeks 12, 19, 26, 33
* Not in patients with significant decrease in pulmonary function
Osteosarcoma and Other Cancer of Bone 201
Grade I/II necrosis (standard histologic response)
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Cisplatin 120 mg /m2 i.v.(20 min inf) d 1 |
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Doxorubicin 25 mg/m2 i.v. (cont inf) d 1 3 wks 8,15,22,27,32 |
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Methotrexate 8000 mg /m2 i.v. wks 11, 14, 18, 21 12000 mg/m2 25, 28, 32, 35 with folinic acid rescue |
* Age > 12 ** Age ≤ 12
BCD
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Bleomycin * 15 mg/m2 i.v. d 1 + 2 |
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Cyclophosphamide 600 mg /m2 i.v. d 1+ 2 |
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Dactinomycin 0.6 mg/m2 i.v. d 1 + 2 |
Weeks 12, 19, 25, 30
* Not in patients with significant decrease in pulmonary function
Literature:
MEYERS et al, J. Clin. Oncol. 10 (1992): 5-15
MEYERS et al, J. Clin. Oncol. 16 (1998): 2452- 2458
ROSEN et al, Cancer 49 (1982): 1221-1230
SOUHAMI et al, Lancet 350 (1997): 911-917
38.2.3 European Osteosarcoma Intergroup (EOI)
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Doxorubicin 25 mg/m2 i.v. (bolus) d 1 - 3 |
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Cisplatin 100 mg /m2 i.v.(cont inf) d 1 |
To be repeated every 3 weeks (3 courses preoperative, surgery on day 63, followed after 2 weeks by 3 courses postoperative)
Literature:
BRAMWELL et al, J. Clin. Oncol. 10 (1992): 1579 1591
SOUHAMI et al, Lancet 350 (1997): 911-917
38.2.4. Salvage therapy
E.g.
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Carboplatin 150 mg/m2 i.v. (1 h inf) d 1 - 4 |
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Etoposide 150 mg /m2 i.v.(1 h inf) d 1 - 4 |
To be repeated every 3 (-4) weeks (max 5 [-6] cycles)
Literature:
WINKLER et al, Cancer Treat. Res. 62 (1993): 269 277
or
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Ifosfamide 3000 mg/m2 i.v. (3 h inf) d 1 4 With mesna uroprotection |
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Etoposide 75 mg /m2 i.v.(1 h inf) d 1 - 4 |
To be repeated every 3 -4 weeks (2 courses)
Literature:
GENTET et al, Eur. J. Cancer 33 (1997): 232- 237
202 Osteosarcoma and Other Cancers of Bone
38.3 Malignant fibrous histiocytoma of bone
E.g.
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Doxorubicin 25 mg/m2 i.v. (bolus) d 1 - 3 |
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Cisplatin 100 mg /m2 i.v.(4 h inf) d 1 |
To be repeated every 3 weeks for 6 cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 d of biopsy , with definite surgery performed after 3 cycles.
Literature:
BRAMWELL et al, J. Clin. Oncol. 17 (1999): 3260 3269