Skip to main content

Advertisement

Log in

Current strategies of chemotherapy in osteosarcoma

  • Review
  • Published:
International Orthopaedics Aims and scope Submit manuscript

Abstract

Osteosarcoma, the most common type of primary malignant tumour that develops in bone, can be classified into several different sub-types. While the majority of osteosarcomas are highly malignant, there are some low-grade variants. Since the introduction of chemotherapy into the multi-modal treatment regimen of high-grade osteosarcoma, its prognosis has impressively improved, with long-term survival being achieved in two-thirds of all patients. This review summarises current chemotherapeutic treatment strategies in classical osteosarcoma and also addresses the indication for chemotherapy in more unusual types and variants. It emphasises the need for treatment in specialised centres and within prospective, multi-institutional trials, amongst which EURAMOS1 and EURO-B.O.S.S are currently active in many European countries.

Résumé

L’ostéosarcome est la tumeur osseuse la plus fréquente, cependant la plupart des ostéosarcomes ont une haute malignité, peu sont de malignité de bas de grade. Depuis l’utilisation de la chimio thérapie dans le traitement des ostéosarcomes de haute malignité, le pronostic a été très nettement amélioré, permettant une survie à long terme chez les deux tiers des patients. Cet article fait la revue des différentes stratégies thérapeutiques de chimiothérapie dans le traitement de l’ostéosarcome et de ses différents types. Il met en évidence que les traitements doivent être réalisés dans des centres spécialisés avec des études prospectives, multi sites, comme celles réalisées avec EURAMOS 1 et EURO-BOSS dans les pays européens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ahmad SA, Patel SR, Ballo MT, Baker TP, Yasko AW, Wang X, Feig BW, Hunt KK, Lin PP, Weber KL, Chen LL, Zagars GK, Pollock RE, Benjamin RS, Pisters PW (2002) Extraosseous osteosarcoma: response to treatment and long-term outcome. J Clin Oncol 20:521–527

    Article  PubMed  Google Scholar 

  2. Bacci G, Ferrari S, Longhi A, Picci P, Mercuri M, Alvegard TA, Saeter G, Donati D, Manfrini M, Lari S, Briccoli A, Forni C, Italian Sarcoma Group/Scandinavian Sarcoma Group (2002) High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study. J Chemother 14:198–206

    Article  PubMed  CAS  Google Scholar 

  3. Bielack SS, Kempf-Bielack B, Winkler K (1996) Osteosarcoma: relationship of response to preoperative chemotherapy and type of surgery to local recurrence. J Clin Oncol 14:683–684

    PubMed  CAS  Google Scholar 

  4. Bielack SS, Kempf-Bielack B, Heise U, Schwenzer D, Winkler K (1999) Combined modality treatment for osteosarcoma occurring as a second malignant disease. Cooperative German-Austrian-Swiss Osteosarcoma Study Group. J Clin Oncol 17:1164–1174

    PubMed  CAS  Google Scholar 

  5. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jurgens H, Winkler K (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20:776–790

    Article  PubMed  Google Scholar 

  6. Bielack SS, Machatschek JN, Flege S, Jurgens H (2004) Delaying surgery with chemotherapy for osteosarcoma of the extremities. Expert Opin Pharmacother 5:1243–1256

    Article  PubMed  Google Scholar 

  7. Cade S (1955) Osteogenic sarcoma; a study based on 133 patients. J Roy Coll Surg Edin 1:79–111

    CAS  Google Scholar 

  8. Enneking WF, Spanier SS, Goodman MA (1980) A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 153:106–120

    PubMed  Google Scholar 

  9. Ferrari S, Briccoli A, Mercuri M, Bertoni F, Picci P, Tienghi A, Del Prever AB, Fagioli F, Comandone A, Bacci G (2003) Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. J Clin Oncol 21:710–715

    Article  PubMed  Google Scholar 

  10. Fletcher CDM, Unni KK, Mertens F (eds) (2002) WHO classification of tumours pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon

  11. Fuchs N, Bielack SS, Epler D, Bieling P, Delling G, Korholz D, Graf N, Heise U, Jurgens H, Kotz R, Salzer-Kuntschik M, Weinel P, Werner M, Winkler K (1998) Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 9:893–899

    Article  PubMed  CAS  Google Scholar 

  12. Goldstein-Jackson SY, Gosheger G, Delling G, Berdel WE, Exner GU, Jundt G, Machatschek JN, Zoubek A, Jurgens H, Bielack SS, Cooperative Osteosarcoma Study Group COSS (2005) Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma. J Cancer Res Clin Oncol 131:520–526

    Article  PubMed  Google Scholar 

  13. Goorin AM, Schwartzentruber DJ, Devidas M, Gebhardt MC, Ayala AG, Harris MB, Helman LJ, Grier HE, Link MP, Pediatric Oncology Group (2003). Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 21:1574–1580

    Article  PubMed  CAS  Google Scholar 

  14. Grimer RJ, Bielack S, Flege S, Cannon SR, Foleras G, Andreeff I, Sokolov T, Taminiau A, Dominkus M, San-Julian M, Kollender Y, Gosheger G, European Musculo Skeletal Oncology Society (2005) Periosteal osteosarcoma – a European review of outcome. Eur J Cancer 41:2806–2811

    Article  PubMed  Google Scholar 

  15. Grimer RJ, Cannon SR, Taminiau AM, Bielack S, Kempf-Bielack B, Windhager R, Dominkus M, Saeter G, Bauer H, Meller I, Szendroi M, Folleras G, San-Julian M, van der Eijken J (2003) Osteosarcoma over the age of forty. Eur J Cancer 39:157–163

    Article  PubMed  CAS  Google Scholar 

  16. Hosalkar HS, Dormans JP (2004) Limb sparing surgery for pediatric musculoskeletal tumors. Pediatr Blood Cancer 42:295–310

    Article  PubMed  Google Scholar 

  17. Jaffe N, Carrasco H, Raymond K, Ayala A, Eftekhari F (2002) Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery? Cancer 95:2202–2210

    Article  PubMed  Google Scholar 

  18. Kempf-Bielack B, Bielack SS, Jurgens H, Branscheid D, Berdel WE, Exner GU, Gobel U, Helmke K, Jundt G, Kabisch H, Kevric M, Klingebiel T, Kotz R, Maas R, Schwarz R, Semik M, Treuner J, Zoubek A, Winkler K (2005) Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 23:559–568

    Article  PubMed  Google Scholar 

  19. Langer T, Stohr W, Paulides M, Kremers A, Dorr HG, Gobel U, Beck JD (2005) Prospective multicenter registration of major late sequelae in sarcoma patients using the Late Effects Surveillance System (LESS). Klin Pediatr 217:176–181

    Article  CAS  Google Scholar 

  20. Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA et al (1986) The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 314:1600–1606

    Article  PubMed  CAS  Google Scholar 

  21. Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, Applewhite A, Vlamis V, Rosen G (1992) Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol 10:5–15

    PubMed  CAS  Google Scholar 

  22. Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML, Conrad E, Ferguson W, Gebhardt M, Goorin AM, Harris MB, Healey J, Huvos A, Link M, Montebello J, Nadel H, Nieder M, Sato J, Siegal G, Weiner M, Wells R, Wold L, Womer R, Grier H (2005) Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol 23:2004–2011

    Article  PubMed  CAS  Google Scholar 

  23. Nakajima H, Sim FH, Bond JR, Unni KK (1997) Small cell osteosarcoma of bone. Review of 72 cases. Cancer 79:2095–2106

    Article  PubMed  CAS  Google Scholar 

  24. Okada K, Unni KK, Swee RG, Sim FH (1999) High grade surface osteosarcoma: a clinicopathologic study of 46 cases. Cancer 85:1044–1054

    Article  PubMed  CAS  Google Scholar 

  25. Picci P, Bacci G, Ferrari S, Mercuri M (1997) Neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone and in osteosarcoma located in the extremities: analogies and differences between the two tumors. Ann Oncol 8:1107–1115

    Article  PubMed  CAS  Google Scholar 

  26. Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M (1994) Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 12:2699–2705

    PubMed  CAS  Google Scholar 

  27. Saeter G, Hoie J, Stenwig AE, Johansson AK, Hannisdal E, Solheim OP (1995) Systemic relapse of patients with osteogenic sarcoma. Prognostic factors for long term survival. Cancer 75:1084–1093

    Article  PubMed  CAS  Google Scholar 

  28. Smeele LE, Kostense PJ, van der Waal I, Snow GB (1997) Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients. J Clin Oncol 15:363–367

    PubMed  CAS  Google Scholar 

  29. Smeland S, Wiebe T, Bohling T, Brosjo O, Jonsson K, Alvegard TA (2004) Chemotherapy in osteosarcoma. The Scandinavian Sarcoma Group experience. Acta Orthop Scand Suppl 75:92–98

    PubMed  CAS  Google Scholar 

  30. Tabone MD, Terrier P, Pacquement H, Brunat-Mentigny M, Schmitt C, Babin-Boilletot A, Mahmoud HH, Kalifa C (1999) Outcome of radiation-related osteosarcoma after treatment of childhood and adolescent cancer: a study of 23 cases. J Clin Oncol 17:2789–2795

    PubMed  CAS  Google Scholar 

  31. Waddell AE, Davis AM, Ahn H, Wunder JS, Blackstein ME, Bell RS (1999) Doxorubicin-cisplatin chemotherapy for high-grade nonosteogenic sarcoma of bone. Comparison of treatment and control groups. Can J Surg 42:190–199

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Prof. Dr. Gernot Jundt, Basel, for providing the photomicrographs of histological sections for Fig. 1, and Lynn Hazelwood for language assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefan S. Bielack.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carrle, D., Bielack, S.S. Current strategies of chemotherapy in osteosarcoma. International Orthopaedics (SICOT) 30, 445–451 (2006). https://doi.org/10.1007/s00264-006-0192-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00264-006-0192-x

Keywords

Navigation