Osteosarcoma
ICD-10 C41.9 · ICD-11 2B51

Next-Line Treatment for High-Grade Osteosarcoma in Patients Aged 40 or Older (or Intolerant to High-Dose Methotrexate) When First-Line AP Chemotherapy Does Not Achieve Target Histological Response

This protocol applies to a specific sub-population: adults with high-grade osteosarcoma who are 40 years of age or older, or who cannot tolerate high-dose methotrexate, and whose disease did not meet the histological response threshold required after first-line neoadjuvant chemotherapy.

Clinical Scenario

Patients aged 40 or older, and those with intolerance to high-dose methotrexate, require adapted treatment strategies. Regimens without high-dose methotrexate may still be effective in this group. Treatment selection must account for individual performance status, cardiac and renal function, and other co-morbidities present.

When First-Line Treatment Has Not Reached Its Goal

The first-line approach for this population — doxorubicin and cisplatin (AP) combined with surgical resection — targets a histological necrosis rate greater than 90% after neoadjuvant chemotherapy. When that threshold is not achieved, escalation to the next treatment step is indicated. This protocol defines that next step.

Treatment Approach (Partial Overview)

Where complete surgical clearance is achievable, resection remains a central consideration. Beyond surgery, the approach incorporates selected systemic options — including certain chemotherapy combinations and multi-targeted agents — chosen on the basis of the individual clinical picture. Radiotherapy may have a palliative role at inoperable sites. The full structured regimen, sequencing, and eligibility criteria are available via the link below.

Instant Access to Structured Evidence-Based Regimens
References
DOI: 10.1038/s41416-024-02868-4

For patients over 40 years and those who cannot tolerate HDMTX, regimens without methotrexate may still be effective.

AP alone is considered suitable therapy, although doses are not standardised and may vary according to performance status, cardiac and renal function and other co-morbidities.

Treatment for recurrent osteosarcoma should include surgical resection if complete surgical clearance is possible.

Multi-targeted tyrosine kinase inhibitors (MTKIs) including cabozantinib, regorafenib and lenvatinib have demonstrated single-agent activity in phase II clinical trials.

Gemcitabine and docetaxel and oral etoposide may offer effective palliation with limited toxicity.

Radiotherapy may palliate inoperable sites.

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