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Osteogenic Sarcoma




Neoadjuvant chemotherapy = Pre-operative

Adjuvant = Post-operative


Both neoadjuvant and adjuvant chemotherapy are important in the treating and preventing relapse in patients with clinically non-metastatic tumors.

Two trials conducted in the 1980s were designed to address the natural history of surgically treated localized, resectable osteosarcoma of the extremity.

  • Less than 20% of patients with localized resectable primary tumors treated with surgery alone survived free of relapse
  • Overall survival statistically inferior with no chemotherapy


The most commonly used agents are:

(used both in the neoadjuvant and adjuvant phases is considered standard treatment)


Other active agents include:

Reference: Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial (JCO 2002 20(2):426-33)


Timing of chemotherapy (neoadjuvant versus adjuvant) does not affect EFS. But neoadjuvant can have advantages:

  • Initial attack on micrometastases (present in 80%)
  • Potential shrinkage of tumor at primary site making limb salvage possible
  • Assessment of sensitivity of tumor to chemotherapy (% of primary tumor necrosis on resection after chemotherapy is an important prognostic factor and if poor response other chemotherapy regimes can be contemplated)


The Children's Oncology Group (COG) performed a prospective randomized trial in newly diagnosed children and young adults with localized osteosarcoma:

1. Testing ifosfamide versus cisplatin.

2. The addition of the biological compound muramyl tripeptide-phosphatidyl ethanolamine encapsulated in liposomes (L-MTP-PE).

  • Neither improved EFS
  • A recent re-analysis of this COG trial cited above (JCO Feb 2008) suggests MTP-PE may improve OS.

Reference: Osteosarcoma: A Randomized, Prospective Trial of the Addition of Ifosfamide and/or Muramyl Tripeptide to Cisplatin, Doxorubicin, and High-Dose Methotrexate


The role of interferon in addition to standard chemotherapy is being testing in a current COG trial based on 40% OS in osteosarcoma treated with surgery and interferon only (Acta Oncol. 2005;44(5):475-80)

Link: Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma


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