Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group

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dc.contributor.authorEbb, David
dc.contributor.authorMeyers, Paul
dc.contributor.authorGrier, Holcombe
dc.contributor.authorBernstein, Mark
dc.contributor.authorGorlick, Richard
dc.contributor.authorLipshultz, Steven E.
dc.contributor.authorKrailo, Mark
dc.contributor.authorDevidas, Meenakshi
dc.contributor.authorBarkauskas, Donald A.
dc.contributor.authorSiegal, Gene P.
dc.contributor.authorFerguson, William Shay
dc.contributor.authorLetson, George Douglas
dc.contributor.authorMarcus, Karen
dc.contributor.authorGoorin, Allen
dc.contributor.authorBeardsley, Peter
dc.contributor.authorMarina, Neyssa
dc.contributor.otherHarvard University
dc.contributor.otherMassachusetts General Hospital
dc.contributor.otherDana-Farber Cancer Institute
dc.contributor.otherMemorial Sloan Kettering Cancer Center
dc.contributor.otherMontefiore Medical Center
dc.contributor.otherUniversity of Miami
dc.contributor.otherChildren's Oncology Group (COG)
dc.contributor.otherUniversity of South Florida
dc.contributor.otherH Lee Moffitt Cancer Center & Research Institute
dc.contributor.otherUniversity of Southern California
dc.contributor.otherLucile Packard Children's Hospital (LPCH)
dc.contributor.otherStanford University
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherSaint Louis University
dc.contributor.otherYale University
dc.contributor.otherDalhousie University
dc.date.accessioned2023-09-28T19:05:28Z
dc.date.available2023-09-28T19:05:28Z
dc.date.issued2012
dc.description.abstractPurpose Despite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression. Patients and Methods Among 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks. Results The 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin. Conclusion Despite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationEbb, D., Meyers, P., Grier, H., Bernstein, M., Gorlick, R., Lipshultz, S. E., Krailo, M., Devidas, M., Barkauskas, D. A., Siegal, G. P., Ferguson, W. S., Letson, G. D., Marcus, K., Goorin, A., Beardsley, P., & Marina, N. (2012). Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children’s Oncology Group. In Journal of Clinical Oncology (Vol. 30, Issue 20, pp. 2545–2551). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2011.37.4546
dc.identifier.doi10.1200/JCO.2011.37.4546
dc.identifier.orcidhttps://orcid.org/0000-0002-2339-719X
dc.identifier.orcidhttps://orcid.org/0000-0003-3857-3368
dc.identifier.orcidhttps://orcid.org/0000-0002-7195-8887
dc.identifier.orcidhttps://orcid.org/0000-0002-1099-3478
dc.identifier.orcidhttps://orcid.org/0000-0001-6146-6101
dc.identifier.orcidhttps://orcid.org/0000-0001-8995-2929
dc.identifier.urihttps://ir.ua.edu/handle/123456789/10838
dc.languageEnglish
dc.language.isoen_US
dc.publisherAmerican Society of Clinical Oncology
dc.subjectHER2-POSITIVE BREAST-CANCER
dc.subjectSTUDY-GROUP PROTOCOLS
dc.subjectCARDIAC TROPONIN-T
dc.subjectMONOCLONAL-ANTIBODY
dc.subjectADJUVANT CHEMOTHERAPY
dc.subjectNATRIURETIC PEPTIDE
dc.subjectPEDIATRIC-PATIENTS
dc.subjectMYOCARDIAL INJURY
dc.subjectRANDOMIZED-TRIAL
dc.subjectPREDICTIVE-VALUE
dc.subjectOncology
dc.titlePhase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Groupen_US
dc.typeArticle
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