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Novel bone cancer drugs: investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and
Pete Anderson1, Lisa Kopp, Nicholas Anderson
1University of Texas, MD Anderson Cancer Center, Department of Pediatrics, Houston, TX 77030-4009, USA. pmanders@mdanderson.org
Background:
New investigational agents and chemotherapy regimens including cyclophosphamide + topotecan, temozolomide + irinotecan, and anti-IGF-1R antibodies in Ewing's sarcoma (ES) and liposomal muramyltripeptide phosphatidylethanolamine (L-MTP-PE), aerosol therapy, and bone-specific agents in osteosarcoma (OS) may improve survival and/or quality of life on 'continuation' therapy.
Objective:
Review of investigational approaches and control paradigms for recurrent or metastatic primary bone tumors.
Methods:
Analyze temozolomide + irinotecan data and review in the context of other newer approaches including antiangiogenesis, anti-IGF-1R antibodies and bisphosphonates for ES. Review some current state-of-the-art approaches for OS including L-MTP-PE, anti-IGF-1R inhibition, aerosol therapies and bone specific agents.
Results/Conclusion:
L-MTP-PE with chemotherapy in OS has been shown to improve survival; compassionate access is available for recurrence and/or metastases. Aerosol therapy (granulocyte-macrophage colony stimulating factor, cisplatin, gemcitabine) for lung metastases is a promising approach to reduce systemic toxicity. The bone-specific agents including denosumab (anti-receptor activator of NF-kappaB ligand antibody) and bisphosphonates may have benefit against giant cell tumor, ES and OS. Anti-IGF-1R antibody SCH717454 has preclinical activity in OS but best effectiveness will most likely be in combination with chemotherapy earlier in therapy. Both temozolomide + irinotecan and cyclophosphamide + topotecan combinations are very active in ES and are likely to be tested with anti-IGF-1R antibodies against ES.
Insights
New treatments like chemotherapy combinations and targeted therapies show promise for improving survival in patients with Ewing sarcoma and osteosarcoma. These investigational agents offer new hope for recurrent or metastatic bone tumors.
Area of Science:
- Oncology
- Pharmacology
- Biomedical Research
Background:
- Investigational agents and chemotherapy regimens are being explored for Ewing sarcoma (ES) and osteosarcoma (OS).
- Current research focuses on novel treatments including cyclophosphamide + topotecan, temozolomide + irinotecan, and anti-IGF-1R antibodies for ES.
- For OS, investigational approaches include liposomal muramyltripeptide phosphatidylethanolamine (L-MTP-PE), aerosol therapy, and bone-specific agents.
Purpose of the Study:
- To review investigational approaches for primary bone tumors.
- To examine control paradigms for recurrent or metastatic bone cancers.
- To assess the potential of novel therapies in improving survival and quality of life.
Main Methods:
- Analysis of temozolomide + irinotecan data for ES.
- Review of newer approaches for ES, including antiangiogenesis, anti-IGF-1R antibodies, and bisphosphonates.
- Review of current state-of-the-art approaches for OS, such as L-MTP-PE, anti-IGF-1R inhibition, aerosol therapies, and bone-specific agents.
Main Results:
- Liposomal muramyltripeptide phosphatidylethanolamine (L-MTP-PE) combined with chemotherapy has demonstrated improved survival in osteosarcoma (OS).
- Aerosol therapy for lung metastases, including granulocyte-macrophage colony stimulating factor, cisplatin, and gemcitabine, shows promise in reducing systemic toxicity.
- Bone-specific agents like denosumab and bisphosphonates may offer benefits for giant cell tumor, ES, and OS.
Conclusions:
- L-MTP-PE with chemotherapy is a proven survival-improving treatment for OS, with compassionate access available.
- Aerosol therapy presents a promising strategy to mitigate systemic toxicity in treating lung metastases.
- Combination therapies, such as temozolomide + irinotecan or cyclophosphamide + topotecan with anti-IGF-1R antibodies, are highly active in ES and warrant further investigation.
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