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Osteosarcoma: The Addition of Muramyl Tripeptide to Chemotherapy Improves Overall Survival—A Report From the Children's Oncology Group
Open accessAbstract
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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“a finding that was reproduced to some extent in humans 67,68 .”
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“There has been a long-standing interest in immune-based therapies centred on the activity of mifamurtide in osteosarcoma in phase II and subsequently on a randomized phase III trial conducted by the Children's Oncology Group 81 .”
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Metadata
- 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
- Venue
- Journal of Clinical Oncology
- Published
- 2008-02-01
- Volume
- 26
- Issue
- 4
- Pages
- 633-638
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- 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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