Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group

Cindy L. Schwartz, Richard Gorlick, Lisa Teot, Mark Krailo, Zhengjia Chen, Allen Goorin, Holcombe E. Grier, Mark L. Bernstein, Paul Meyers

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Abstract

Purpose: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. Patients and Methods: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease. Results: P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P = .61). Conclusion: Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.

Original languageEnglish (US)
Pages (from-to)2057-2062
Number of pages6
JournalJournal of Clinical Oncology
Volume25
Issue number15
DOIs
StatePublished - May 20 2007
Externally publishedYes

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Multiple Drug Resistance
Osteosarcoma
P-Glycoprotein
Neoplasms
Disease-Free Survival
Survival
Paraffin
Young Adult
Necrosis
Monoclonal Antibodies
Outcome Assessment (Health Care)
Biopsy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Schwartz, C. L., Gorlick, R., Teot, L., Krailo, M., Chen, Z., Goorin, A., ... Meyers, P. (2007). Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group. Journal of Clinical Oncology, 25(15), 2057-2062. https://doi.org/10.1200/JCO.2006.07.7776

Multiple drug resistance in osteogenic sarcoma : INT0133 from the Children's Oncology Group. / Schwartz, Cindy L.; Gorlick, Richard; Teot, Lisa; Krailo, Mark; Chen, Zhengjia; Goorin, Allen; Grier, Holcombe E.; Bernstein, Mark L.; Meyers, Paul.

In: Journal of Clinical Oncology, Vol. 25, No. 15, 20.05.2007, p. 2057-2062.

Research output: Contribution to journalArticle

Schwartz, CL, Gorlick, R, Teot, L, Krailo, M, Chen, Z, Goorin, A, Grier, HE, Bernstein, ML & Meyers, P 2007, 'Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group', Journal of Clinical Oncology, vol. 25, no. 15, pp. 2057-2062. https://doi.org/10.1200/JCO.2006.07.7776
Schwartz, Cindy L. ; Gorlick, Richard ; Teot, Lisa ; Krailo, Mark ; Chen, Zhengjia ; Goorin, Allen ; Grier, Holcombe E. ; Bernstein, Mark L. ; Meyers, Paul. / Multiple drug resistance in osteogenic sarcoma : INT0133 from the Children's Oncology Group. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 15. pp. 2057-2062.
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abstract = "Purpose: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. Patients and Methods: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease. Results: P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59{\%} at 4 years versus 61{\%} at 4 years for patients with C-494-negative tumors (P = .79), or 58{\%} at 4 years versus 61{\%} at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82{\%} at 4 years versus 82{\%} at 4 years for patients with C-494-negative tumors (P = .61). Conclusion: Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.",
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AU - Chen, Zhengjia

AU - Goorin, Allen

AU - Grier, Holcombe E.

AU - Bernstein, Mark L.

AU - Meyers, Paul

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N2 - Purpose: Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. Patients and Methods: From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease. Results: P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1-positive versus JSB-1-negative tumors (P = .65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P = .61). Conclusion: Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.

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