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:
- Cisplatin
- Doxorubicin
- High dose methotrexate
(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.
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
