Skip to main content

Advertisement

Log in

Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis

  • Research Article
  • Published:
Tumor Biology

Abstract

The mortality and progression rates in osteosarcoma differ depending on the presence of metastasis. A decision model would be useful for estimating long-term effectiveness of treatment with limited clinical trial data. The aim of this study was to explore the lifetime effectiveness of the addition of mifamurtide to chemotherapy for patients with metastatic and nonmetastatic osteosarcoma. The target population was osteosarcoma patients with or without metastasis. A Markov process model was used, whose time horizon was lifetime with a starting age of 13 years. There were five health states: disease-free (DF), recurrence, post-recurrence disease-free, post-recurrence disease-progression, and death. Transition probabilities of the starting state, DF, were calculated from the INT-0133 clinical trials for chemotherapy with and without mifamurtide. Quality-adjusted life-years (QALY) increased upon addition of mifamurtide to chemotherapy by 10.5 % (10.13 and 9.17 QALY with and without mifamurtide, respectively) and 45.2 % (7.23 and 4.98 QALY with and without mifamurtide, respectively) relative to the lifetime effectiveness of chemotherapy in nonmetastatic and metastatic osteosarcoma, respectively. Life-years gained (LYG) increased by 10.1 % (13.10 LYG with mifamurtide and 11.90 LYG without mifamurtide) in nonmetastatic patients and 42.2 % (9.43 LYG with mifamurtide and 6.63 LYG without mifamurtide) in metastatic osteosarcoma patients. The Markov model analysis showed that chemotherapy with mifamurtide improved the lifetime effectiveness compared to chemotherapy alone in both nonmetastatic and metastatic osteosarcoma. Relative effectiveness of the therapy was higher in metastatic than nonmetastatic osteosarcoma over lifetime. However, absolute lifetime effectiveness was higher in nonmetastatic than metastatic osteosarcoma.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20(3):776–90.

    Article  PubMed  Google Scholar 

  2. Bielack S, Carrle D, Casali PG, On behalf of the ESMO Guidelines Working Group. Osteosarcoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Supplement 4):iv137–9.

    Article  Google Scholar 

  3. NCCN clinical practice guidelines in oncology: bone cancer. version 2.2012.

  4. Ando K, Mori K, Corradini N, Redini F, Heymann D. Mifamurtide for the treatment of nonmetastatic osteosarcoma. Expert Opin Pharmacother. 2011;12(2):285–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML, et al. Osteosarcoma: a randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol. 2005;23(9):2004–11.

    Article  CAS  PubMed  Google Scholar 

  6. Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival—a report from the Children’s Oncology Group. J Clin Oncol. 2008;26(4):633–8.

    Article  CAS  PubMed  Google Scholar 

  7. Chou AJ, Kleinerman ES, Krailo MD, Chen Z, Betcher DL, Healey JH, et al. Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: a report from the Children’s Oncology Group. Cancer. 2009;115(22):5339–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bielack SS, Kempf-Bielack B, Branscheid D, Carrle D, Friedel G, Helmke K, et al. Second and subsequent recurrences of osteosarcoma: presentation, treatment, and outcomes of 249 consecutive cooperative osteosarcoma study group patients. J Clin Oncol. 2009;27(4):557–65.

    Article  PubMed  Google Scholar 

  9. Kempf-Bielack B, Bielack SS, Jürgens H, Branscheid D, Berdel WE, Exner GU, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005;23(3):559–68.

    Article  PubMed  Google Scholar 

  10. Johal S, Ralston S, Knight C. Mifamurtide for high-grade, resectable, nonmetastatic osteosarcoma following surgical resection: a cost-effectiveness analysis. Value Health. 2013;16(8):1123–32.

    Article  PubMed  Google Scholar 

  11. Song HJ, Lee EK, Lee JA, Kim HL, Jang KW. The addition of mifamurtide to chemotherapy improves lifetime effectiveness in children with osteosarcoma: a Markov model analysis. Tumour Biol. 2014;35(9):8771–9.

    Article  CAS  PubMed  Google Scholar 

  12. The guideline of pharmacoeconomics in South Korea. Health Insurance Review and Assessment. 2011.

  13. Lee JA, Kim MS, Kim DH, Lim JS, Park KD, Song WS, et al. Risk stratification based on the clinical factors at diagnosis is closely related to the survival of localized osteosarcoma. Pediatr Blood Cancer. 2009;52:340–5.

    Article  PubMed  Google Scholar 

  14. Briggs A, Claxton K, Sculpher M. Decision modeling for health economic evaluation. Oxford: Oxford University Press; 2006.

    Google Scholar 

  15. Complete Life Table 2010. Korean Statistical Office. http://kostat.go.kr (2010). Accessed 21 Nov 2013.

  16. Yu G, Sung G. Diagnosis and treatment of osteosarcoma. Chosun Ilbo, Samsung Medical Center; 2006.

  17. Lee YJ, Lee HJ, Kim DH, Lim JS, Lee JH, Park KD, et al. Outcome after relapse in childhood and adolescent osteosarcoma: single institution experience in Korea. Korean J Pediatr. 2008;51(1):78–83.

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant awarded by Takeda Pharmaceuticals Korea Co., Ltd., Seoul, Republic of Korea.

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eui-Kyung Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, H.J., Lee, J.A., Han, E. et al. Lifetime effectiveness of mifamurtide addition to chemotherapy in nonmetastatic and metastatic osteosarcoma: a Markov process model analysis. Tumor Biol. 36, 6773–6779 (2015). https://doi.org/10.1007/s13277-015-3405-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3405-3

Keywords

Navigation