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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):633-8JC

Abstract

PURPOSE

To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma.

PATIENTS AND METHODS

Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival.

RESULTS

In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96).

CONCLUSION

The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.

Authors+Show Affiliations

Children's Oncology Group, Arcadia, CA, USA. meyersp@mskcc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18235123

Citation

Meyers, Paul A., et al. "Osteosarcoma: the Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival--a Report From the Children's Oncology Group." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 26, no. 4, 2008, pp. 633-8.
Meyers PA, Schwartz CL, Krailo MD, 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.
Meyers, P. A., Schwartz, C. L., Krailo, M. D., Healey, J. H., Bernstein, M. L., Betcher, D., ... Grier, H. E. (2008). Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 26(4), pp. 633-8. doi:10.1200/JCO.2008.14.0095.
Meyers PA, 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 Feb 1;26(4):633-8. PubMed PMID: 18235123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group. AU - Meyers,Paul A, AU - Schwartz,Cindy L, AU - Krailo,Mark D, AU - Healey,John H, AU - Bernstein,Mark L, AU - Betcher,Donna, AU - Ferguson,William S, AU - Gebhardt,Mark C, AU - Goorin,Allen M, AU - Harris,Michael, AU - Kleinerman,Eugenie, AU - Link,Michael P, AU - Nadel,Helen, AU - Nieder,Michael, AU - Siegal,Gene P, AU - Weiner,Michael A, AU - Wells,Robert J, AU - Womer,Richard B, AU - Grier,Holcombe E, AU - ,, PY - 2008/2/1/pubmed PY - 2008/2/20/medline PY - 2008/2/1/entrez SP - 633 EP - 8 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 26 IS - 4 N2 - PURPOSE: To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma. PATIENTS AND METHODS: Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival. RESULTS: In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96). CONCLUSION: The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/18235123/Osteosarcoma:_the_addition_of_muramyl_tripeptide_to_chemotherapy_improves_overall_survival__a_report_from_the_Children's_Oncology_Group_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2008.14.0095?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -