Osteosarcoma: The addition of muramyl tripeptide to chemotherapy improves overall survival - A report from the children's oncology group Journal Article


Authors: Meyers, P. A.; Schwartz, C. L.; Krailo, M. D.; Healey, J. H.; Bernstein, M. L.; Betcher, D.; Ferguson, W. S.; Gebhardt, M. C.; Goorin, A. M.; Harris, M.; Kleinerman, E.; Link, M. P.; Nadel, H.; Nieder, M.; Siegal, G. P.; Weiner, M. A.; Wells, R. J.; Womer, R. B.; Grier, H. E.
Article Title: Osteosarcoma: The addition of muramyl tripeptide to chemotherapy improves overall survival - A report from the children's oncology group
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. © 2008 by American Society of Clinical Oncology.
Keywords: osteosarcoma; adolescent; adult; cancer survival; child; controlled study; preschool child; bone neoplasms; child, preschool; disease-free survival; bone tumor; cancer surgery; survival rate; major clinical study; overall survival; clinical trial; mortality; cisplatin; doxorubicin; cancer combination chemotherapy; unspecified side effect; cancer patient; comparative study; disease free survival; methotrexate; drug megadose; antineoplastic agent; prospective study; metastasis; controlled clinical trial; neoplasm recurrence, local; randomized controlled trial; antineoplastic combined chemotherapy protocols; lung neoplasms; ifosfamide; childhood cancer; confidence interval; lung tumor; statistical significance; infant; tumor recurrence; hazard ratio; muramyl tripeptide
Journal Title: Journal of Clinical Oncology
Volume: 26
Issue: 4
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2008-02-01
Start Page: 633
End Page: 638
Language: English
DOI: 10.1200/jco.2008.14.0095
PUBMED: 18235123
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 87" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Paul Meyers
    244 Meyers
  2. John H Healey
    374 Healey