Cited by 756Sarcoma Diagnosis and TreatmentBone Tumor Diagnosis and TreatmentsOvarian cancer diagnosis and treatment

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Osteosarcoma: The Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival—A Report From the Children's Oncology Group

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Meyers, Paul A., Schwartz, Cindy L., Krailo, Mark D., Healey, John H., Bernstein, Mark L., Betcher, Donna, Ferguson, William S., Gebhardt, Mark C., Goorin, Allen M., Harris, Michael, Kleinerman, Eugenie, Link, Michael P., Nadel, Helen, Nieder, Michael, Siegal, Gene P., Weiner, Michael A., Wells, Robert J., Womer, Richard B., Grier, Holcombe E.·2008·Journal of Clinical Oncology

DOI 10.1200/jco.2008.14.0095

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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 × 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.

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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.
Affiliations: Children's Oncology Group (US)
ORCID: Meyers, Paul A.
Schwartz, Cindy L.
Krailo, Mark D.
Healey, John H.
Bernstein, Mark L.
Ferguson, William S.
Kleinerman, Eugenie
Nadel, Helen
Siegal, Gene P.
Womer, Richard B.
Grier, Holcombe E.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2008-02-01
Volume: 26
Issue: 4
Pages: 633-638
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2008.14.0095
OpenAlex: W2103405666
Cited by: 752
References: 20
Citations by year: 2026: 21 · 2025: 30 · 2024: 30 · 2023: 31 · 2022: 40 · 2021: 51 · 2020: 70 · 2019: 39 · 2018: 38 · 2017: 55 · 2016: 49 · 2015: 50 · 2014: 57 · 2013: 46 · 2012: 36
FWCI: 33.48
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Funders: Children’s Oncology Group
National Institutes of Health (CA98543)
National Cancer Institute (U10CA098543, CA-98543)
Topics: Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone Tumor Diagnosis and Treatments
Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
Keywords: osteosarcoma, muramyl tripeptide, ifosfamide, cisplatin, doxorubicin, methotrexate, event-free survival, overall survival, pediatric cancer chemotherapy, immunomodulatory therapy, surgical resection
MeSH terms: Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols, Bone Neoplasms, Child, Child, Preschool, Cisplatin, Doxorubicin, Female, Humans, Ifosfamide, Infant, Lung Neoplasms, Male, Methotrexate, Neoplasm Recurrence, Local, Osteosarcoma, Survival Rate, Disease-Free Survival

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Osteosarcoma: The Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival—A Report From the Children's Oncology Group

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