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

David Ebb, Paul Meyers, Holcombe Grier, Mark Bernstein, Richard Gorlick, Steven E. Lipshultz, Mark Krailo, Meenakshi Devidas, Donald A. Barkauskas, Gene P. Siegal, William Shay Ferguson, George Douglas Letson, Karen Marcus, Allen Goorin, Peter Beardsley, Neyssa Marina

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)2545-2551
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number20
DOIs
StatePublished - Jul 10 2012

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Osteosarcoma
Drug Therapy
Therapeutics
Dexrazoxane
Doxorubicin
Anthracyclines
Disease-Free Survival
Trastuzumab
human ERBB2 protein
Survival Rate
Ifosfamide
Survival
Etoposide
Methotrexate
Cisplatin
Immunohistochemistry
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Ebb, David; Meyers, Paul; Grier, Holcombe; Bernstein, Mark; Gorlick, Richard; Lipshultz, Steven E.; Krailo, Mark; Devidas, Meenakshi; Barkauskas, Donald A.; Siegal, Gene P.; Ferguson, William Shay; Letson, George Douglas; Marcus, Karen; Goorin, Allen; Beardsley, Peter; Marina, Neyssa.

In: Journal of Clinical Oncology, Vol. 30, No. 20, 10.07.2012, p. 2545-2551.

Research output: Contribution to journalArticle

Ebb, D, Meyers, P, Grier, H, Bernstein, M, Gorlick, R, Lipshultz, SE, Krailo, M, Devidas, M, Barkauskas, DA, Siegal, GP, Ferguson, WS, Letson, GD, 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', Journal of Clinical Oncology, vol. 30, no. 20, pp. 2545-2551. https://doi.org/10.1200/JCO.2011.37.4546
Ebb, David ; Meyers, Paul ; Grier, Holcombe ; Bernstein, Mark ; Gorlick, Richard ; Lipshultz, Steven E. ; Krailo, Mark ; Devidas, Meenakshi ; Barkauskas, Donald A. ; Siegal, Gene P. ; Ferguson, William Shay ; Letson, George Douglas ; Marcus, Karen ; Goorin, Allen ; Beardsley, Peter ; Marina, Neyssa. / 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. 2012 ; Vol. 30, No. 20. pp. 2545-2551.
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title = "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",
abstract = "Purpose: 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.",
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T1 - Phase II trial of trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression

T2 - A report from the children's oncology group

AU - Ebb, David

AU - Meyers, Paul

AU - Grier, Holcombe

AU - Bernstein, Mark

AU - Gorlick, Richard

AU - Lipshultz, Steven E.

AU - Krailo, Mark

AU - Devidas, Meenakshi

AU - Barkauskas, Donald A.

AU - Siegal, Gene P.

AU - Ferguson, William Shay

AU - Letson, George Douglas

AU - Marcus, Karen

AU - Goorin, Allen

AU - Beardsley, Peter

AU - Marina, Neyssa

PY - 2012/7/10

Y1 - 2012/7/10

N2 - Purpose: 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.

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