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

Pete Anderson, Lisa Kopp, Nicholas Anderson, Kathleen Cornelius, Cynthia Herzog, Dennis Hughes, Winston Huh

Research output: Contribution to journalReview article

53 Scopus citations

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 muramyl-tripeptide 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 includind 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 spefic agennts. 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-κB 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.

Original languageEnglish (US)
Pages (from-to)1703-1715
Number of pages13
JournalExpert Opinion on Investigational Drugs
Volume17
Issue number11
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

Keywords

  • Anti-IGF-1R
  • Antiangiogenesis
  • Bisphosphonates
  • Bone cancer
  • Cyclophosphamide
  • Denosumab
  • Ewing's sarcoma
  • Giant cell tumor
  • High-dose methotrexate with glucarpidase
  • Imm Ther
  • Insulin growth factor receptor
  • Irinotecan
  • L-MTP-PE
  • Lung metastases
  • Osteosarcoma
  • R1507
  • SCH717454
  • Temozolomide
  • Topotecan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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