Skip to main content
SpringerLink
Log in

Doxorubicin: Role in the treatment of osteosarcoma

  • Chapter
Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies

Part of the book series: Cancer Treatment and Research ((CTAR,volume 62))

Abstract

The objective of this chapter is to review the role that doxorubicin (DOX), one of the most active single agents for the treatment of osteosarcoma, has played in the neoadjuvant and adjuvant treatment of osteosarcoma during the past several decades. A brief review of the mechanism of action, pharmacokinetics, and pharmacodynamics of DOX will be presented, since an understanding of these parameters is essential to the optimal use of this agent. Results from recent clinical trials that have incorporated DOX (either alone or in combination chemotherapy regimens) will then be reviewed, and potential strategies to maximize the antitumor potential of DOX in future combination regimens will be discussed. The comprehensive review published in 1988 by Grem et al. [1] will be updated, and reference citation will be limited to the recent literature (1988 to the present).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Grem J, King S, Wittes R, Leyland-Jones B. The role of methotrexate in osteosarcoma. J Natl Cancer Inst 80:626–656, 1988.

    Article  PubMed  CAS  Google Scholar 

  2. Balis F, Holcenberg J, Poplack D. General principles of chemotherapy. In: Principles and Practice of Pediatric Oncology. Pizzo P, Poplack D, Eds. J.B. Lipincott, Philadelphia, 1989, pp 165–205.

    Google Scholar 

  3. Sinha B, Politi P. Anthracyclines. In: Cancer Chemotherapy and Biological Response Modifiers Annual 11. Pinedo M, Chabner B, Longo D, Eds. Elsevier Science, Amsterdam, 1990, pp 45–57.

    Google Scholar 

  4. Epstein R. Drug-induced DNA damage and tumor chemosensitivity. J Clin Oncol 8:2062–2084, 1990.

    PubMed  CAS  Google Scholar 

  5. Myers C, Chabner B. Anthracyclines. In: Cancer Chemotherapy Principles & Practice. Chabner B, Collins J, Eds., J.b. Lippincott, Philadelphia, 1990, pp 356–381.

    Google Scholar 

  6. Frank S, Mathiesen D, Szurszewski M, et al. Preclinical pharmacology of the anthrapyrazole analog oxantrazole (NSC-349174, Piroxantrone). Cancer Chemother Pharmacol 23:213–218, 1989.

    Article  PubMed  CAS  Google Scholar 

  7. Danks M, Yalowich J, Beck W. Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26). Cancer Res 47:1297–1301, 1987.

    PubMed  CAS  Google Scholar 

  8. Danks M, Schmidt C, Cirtain M, et al. Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26. Biochemistry 27:8861–8869, 1988.

    Article  PubMed  CAS  Google Scholar 

  9. Wolverton J, Danks M, Schmidt C, Beck W. Genetic characterization of the multidrug-resistant phenotype of VM-26-resistant human leukemic cells. Cancer Res 49:2422–2426, 1989.

    PubMed  CAS  Google Scholar 

  10. Dusre L, Mimnaugh E, Myers C, Sinha B. Potentiation of doxorubicin cytotoxicity by buthione sulfoximine in multidrug-resistant human breast tumor cells. Cancer Res 49:511–515, 1989.

    PubMed  CAS  Google Scholar 

  11. Mitchell J, Cook J, DeGraff W, et al. Glutathione modulation in cancer treatment: will it work? Int J Radiat Oncology Biol Phys 16:1289–1295, 1989.

    Article  CAS  Google Scholar 

  12. Baas F, Jongsma A, Broxterman H, et al. Non-P-glycoprotein mediated mechanism for multidrug resistance precedes P-glycoprotein expression during in vitro selection for doxorubicin resistance in a human lung cancer cell line. Cancer Res 50:5392–5398, 1990.

    PubMed  CAS  Google Scholar 

  13. Keizer H, Schuurhuis G, Broxterman H, et al. Correlation of multidrug resistance with decreased drug accumulation, altered subcellular drug distribution and increased P-glycoprotein expression in cultured SW-1573 human lung tumor cells. Cancer Res 49:2988–2993, 1989.

    PubMed  CAS  Google Scholar 

  14. Beck W. Unknotting the complexities of multidrug resistance: the involvement of DNA topoisomerases in drug action and resistance. J Natl Cancer Inst 81:1683–1685, 1989.

    Article  PubMed  CAS  Google Scholar 

  15. Morrow C, Cowan K. Mechanisms and clinical significance of multidrug resistance. Oncology 2:55–68, 1988.

    PubMed  CAS  Google Scholar 

  16. Dalton W, Grogan T, Meltzer P, et al. Drug-resistance in multiple myeloma and non-Hodgkin’s lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J Clin Oncol 7:415–424, 1989.

    PubMed  CAS  Google Scholar 

  17. Ozols R, Cunnion R, Klecker R, et al. Verapamil and adriamycin in the treatment of drug-resistant cancer patients. J Clin Oncol 5:641–647, 1987.

    PubMed  CAS  Google Scholar 

  18. Miller T, Grogan T, Dalton W, et al. P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol 9:17–24, 1991.

    PubMed  CAS  Google Scholar 

  19. Cairo M. Clinical trial of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. Cancer Res 49:1063–1066, 1989.

    PubMed  CAS  Google Scholar 

  20. Miller R, Bukowski R, Budd G, et al. Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial. J Clin Oncol 6:880–888, 1988.

    PubMed  CAS  Google Scholar 

  21. Chabner B, Wilson W. Reversal of multidrug resistance. J Clin Oncol 9:4–6, 1991.

    PubMed  CAS  Google Scholar 

  22. Scudder S, Brown J, Sikic B. DNA cross-linking and cytotoxicity of the alkylating cyanomorpholino derivative of doxorubicin in multidrug-resistant cells. J Natl Cancer Inst 80:1294–1298, 1988.

    Article  PubMed  CAS  Google Scholar 

  23. Bielack S, Erttmann R, Winkler K, Landbeck G. Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy. Eur J Cancer Clin Oncol 25:873–882, 1989.

    Article  PubMed  CAS  Google Scholar 

  24. Chawla S, Rosen G, Lowenbraun S, et al. Role of high dose ifosphamide in recurrent osteosarcoma. Proc Am Soc Clin Oncol 9:310, 1990.

    Google Scholar 

  25. Meyer W, Pratt C, Rao B, et al. Preliminary results of a trial for previously untreated patients with osteosarcoma including ifosfamide as initial therapy. Proc Am Soc Cancer Res 31:201, 1990.

    Google Scholar 

  26. Winkler K, Beron G, Delling G, et al. Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol 6:329–337, 1988.

    PubMed  CAS  Google Scholar 

  27. Winkler K, Bielack S, Delling G, et al. Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate and ifosfamide on histologic tumor response in osteosarcoma (Study COSS-86). Cancer 66:1703–1710, 1990.

    Article  PubMed  CAS  Google Scholar 

  28. Benjamin R, Raymond A, Carrasco C, et al. Primary chemotherapy of osteosarcoma of the extremities with systemic adriamycin and intraarterial cis-platinum. Proc Am Soc Clin Oncol 8:322, 1989.

    Google Scholar 

  29. Bacci G, Picci P, Ruggieri P, et al. Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities. Cancer 65:2539–2553, 1990.

    Article  PubMed  CAS  Google Scholar 

  30. Bacci G, Picci P, Avella M, et al. The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively. 2:127–135, 1990.

    CAS  Google Scholar 

  31. Meyers P, Casper E, Sison B, et al. Osteogenic sarcoma: a prospective randomized trial of intensive pre-operative chemotherapy vs. chemotherapy guided by histologic response to pre-operative chemotherapy. Proc Am Soc Clin Oncol 8:304, 1989.

    Google Scholar 

  32. Miser J, Pritchard D, Sim F, et al. Treatment of osteosarcoma with a new chemotherapy regimen of ifosfamide, adriamycin, and high dose methotrexate. Proc Am Soc Clin Oncol 9:295, 1990.

    Google Scholar 

  33. Link M, Goorin M, Horowitz M, et al. The multi-institutional osteosarcoma study (MIOS): update and analysis of prognostic factors. Med Pediatr Oncol 17:301–302, 1990.

    Google Scholar 

  34. Prasad R, Bacci G, Picci P, et al. Neoadjuvant chemotherapy of high grade osteosarcoma and prognostic significance of percentage tumor necrosis and drug dose intensity. In: Adjuvant Treatment of Cancer VI. Salmon S, Ed. W.B. Saunders, Philadelphia, 1990, pp 574–579.

    Google Scholar 

  35. Provisor A, Nachman J, Krailo M, et al. Treatment of non-metastatic osteogenic sarcoma of the extremities with pre-and post-operative chemotherapy. Proc Am Soc Clin Oncol 6:217, 1987.

    Google Scholar 

  36. Hudson M, Jaffe M, Jaffe N, et al. Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. J Clin Oncol 8:1988–1997, 1990.

    PubMed  CAS  Google Scholar 

  37. Hortobagyi G, Frye D, Buzdar A, et al. Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma. Cancer 63:37–45, 1989.

    Article  PubMed  CAS  Google Scholar 

  38. Langevin A, Pierro A, Liu P, et al. Adriamycin and cis-platinum administered by continuous infusion preoperatively in hepatoblastoma unresectable at presentation. Med Pediatr Oncol 18:181–184, 1990.

    Article  PubMed  CAS  Google Scholar 

  39. Ortega J, Ablin A, Haas J, et al. Continuous infusion adriamycin-cisplatin for the treatment of pediatric liver tumors. Proc Am Soc Clin Oncol 9:295, 1990.

    Google Scholar 

  40. Rajagopolan S, Politi P, Sinka B, Meyers C. Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity. Cancer Res 48:4766–4769, 1988.

    Google Scholar 

  41. Herman E, Ferrans V, Young R, Hamlin R. Effect of pretreatment with ICRF-187 on the total cumulative dose of doxorubicin tolerated by beagle dogs. Cancer Res 48:6918–6925, 1988.

    PubMed  CAS  Google Scholar 

  42. Speyer J, Green M, Kramer E, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. N Engl J Med 319:745–752, 1988.

    Article  PubMed  CAS  Google Scholar 

  43. Speyer J, Walsh C, Downey A, et al. A phase I trial of escalating doxorubicin with ICRF-187 for cardioprotection and GMCSF for bone marrow support. Proc Am Soc Clin Oncol 9:42, 1990.

    Google Scholar 

  44. Storm G, van Hoesel G, de Groot G, et al. A comparative study on the antitumor effect, cardiotoxicity and nephrotoxicity of doxorubicin given as a bolus, continuous infusion or entrapped in liposomes in the Lou/M Wsl rat. Cancer Chemother Pharmacol 24:341–348, 1989.

    Article  PubMed  CAS  Google Scholar 

  45. Rahman A, Treat J, Roh J, et al. A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin. J Clin Oncol 8:1093–1100, 1990.

    PubMed  CAS  Google Scholar 

  46. Gabizon A, Peretz T, Sulkes A, et al. Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study. Eur J Cancer Clin Oncol 25:1795–1803, 1989.

    Article  PubMed  CAS  Google Scholar 

  47. Treat J, Greenspan A, Frost D, et al. Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study. J Natl Cancer Inst 82:1706–1710, 1990.

    Article  PubMed  CAS  Google Scholar 

  48. Bronchud M, Howell A, Crowther D, et al. The use of granulocyte colony-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer 60:121–125, 1989.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Oncology, Walter Reed Army Medical Center, Room 1K, Washington, DC, 20307, USA

    Susan M. Blaney

  2. Clinical Investigation Branch, National Cancer Institute, Bethesda, MD, 20892, USA

    Malcolm A. Smith

  3. Medicine Branch, National Cancer Institute, Bethesda, MD, 20892, USA

    Jean L. Grem

Authors
  1. Susan M. Blaney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Malcolm A. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean L. Grem
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical College of Ohio at Toledo, USA

    G. Bennett Humphrey

  2. University of Groningen, Netherlands

    H. Schraffordt Koops , W. M. Molenaar  & A. Postma ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media New York

About this chapter

Cite this chapter

Blaney, S.M., Smith, M.A., Grem, J.L. (1993). Doxorubicin: Role in the treatment of osteosarcoma. In: Humphrey, G.B., Koops, H.S., Molenaar, W.M., Postma, A. (eds) Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies. Cancer Treatment and Research, vol 62. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3518-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-3518-8_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6561-7

  • Online ISBN: 978-1-4615-3518-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation