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

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 2008
Externally publishedYes

Fingerprint

irinotecan
Investigational Drugs
temozolomide
Bone Neoplasms
Ewing's Sarcoma
Osteosarcoma
Sarcoma
Bone and Bones
Aerosols
Antibodies
Topotecan
Diphosphonates
gemcitabine
Cyclophosphamide
Neoplasm Metastasis
Drug Therapy
Giant Cell Tumors
Therapeutics
Granulocyte-Macrophage Colony-Stimulating Factor
Secondary Prevention

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)

Cite this

Novel bone cancer drugs : Investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma). / Anderson, Pete; Kopp, Lisa M; Anderson, Nicholas; Cornelius, Kathleen; Herzog, Cynthia; Hughes, Dennis; Huh, Winston.

In: Expert Opinion on Investigational Drugs, Vol. 17, No. 11, 11.2008, p. 1703-1715.

Research output: Contribution to journalArticle

Anderson, Pete ; Kopp, Lisa M ; Anderson, Nicholas ; Cornelius, Kathleen ; Herzog, Cynthia ; Hughes, Dennis ; Huh, Winston. / Novel bone cancer drugs : Investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma). In: Expert Opinion on Investigational Drugs. 2008 ; Vol. 17, No. 11. pp. 1703-1715.
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AU - Anderson, Pete

AU - Kopp, Lisa M

AU - Anderson, Nicholas

AU - Cornelius, Kathleen

AU - Herzog, Cynthia

AU - Hughes, Dennis

AU - Huh, Winston

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N2 - 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.

AB - 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.

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KW - L-MTP-PE

KW - Lung metastases

KW - Osteosarcoma

KW - R1507

KW - SCH717454

KW - Temozolomide

KW - Topotecan

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