Novel bone cancer drugs: investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma).

Abstract

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.

• Authors: Pete Anderson, Lisa Kopp, Nicholas Anderson, Kathleen Cornelius, Cynthia Herzog, Dennis Hughes, Winston Huh
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 17 Issue 11 Pg. 1703-15 (Nov 2008) ISSN: 1744-7658 [Electronic] England
• PMID: 18922107 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents

Topics

• Animals
• Antineoplastic Agents (immunology, therapeutic use)
• Drug Evaluation, Preclinical
• Humans
• Immunotherapy
• Neoplasm Metastasis (pathology)
• Osteosarcoma (diagnostic imaging, drug therapy, immunology, pathology)
• Radiography
• Sarcoma, Ewing (diagnostic imaging, drug therapy, immunology, pathology)